Colorectal Cancer

Screening for colorectal cancer (CRC) with colonoscopy enables the identification and removal of CRC precursors (colonic adenomas) and has been associated with reduced risk of CRC incidence and mortality.^1-3 Furthermore, there is consensus that diet and lifestyle may be associated with forestalling CRC pathogenesis at the intermediate adenoma stages.^4-7 However, studies have shown that US veterans have poorer diet quality and a higher risk for neoplasia compared with nonveterans, reinforcing the need for tailored clinical approaches.^8,9 Combining screening with conversations about modifiable environmental and lifestyle risk factors, such as poor diet, is a highly relevant and possibly easily leveraged prevention for those at high risk. However, there is limited evidence for any particular dietary patterns or dietary features that are most important over time.⁷

Several dietary components have been shown to be associated with CRC risk,10 either as potentially chemopreventive (fiber, fruits and vegetables,¹¹ dairy,¹² supplemental vitamin D,¹³ calcium,¹⁴ and multivitamins¹⁵) or carcinogenic (red meat¹⁶ and alcohol¹⁷). Previous studies of veterans have similarly shown that higher intake of fiber and vitamin D reduced risk, and red meat is associated with an increased risk for finding CRC precursors during colonoscopy.¹⁸ However, these dietary categories are often analyzed in isolation. Studying healthy dietary patterns in aggregate may be more clinically relevant and easier to implement for prevention of CRC and its precursors.^19-21 Healthy dietary patterns, such as the US Dietary Guidelines for Americans represented by the Healthy Eating Index (HEI), the Mediterranean diet (MD), and the Dietary Approaches to Stop Hypertension (DASH) diet, have been associated with lower risk for chronic disease.^22-24 Despite the extant literature, no known studies have compared these dietary patterns for associations with risk of CRC precursor or CRC development among US veterans undergoing long-term screening and follow-up after a baseline colonoscopy.

The objective of this study was to test for associations between baseline scores of healthy dietary patterns and the most severe colonoscopy findings (MSCFs) over ≥ 10 years following a baseline screening colonoscopy in veterans.

Methods

Participants in the Cooperative Studies Program (CSP) #380 cohort study included 3121 asymptomatic veterans aged 50 to 75 years at baseline who had consented to initial screening colonoscopy between 1994 and 1997, with subsequent follow-up and surveillance.²⁵ Prior to their colonoscopy, all participants completed a baseline study survey that included questions about cancer risk factors including family history of CRC, diet, physical activity, and medication use.

Included in this cross-sectional analysis were data from a sample of veteran participants of the CSP #380 cohort with 1 baseline colonoscopy, follow-up surveillance through 2009, a cancer risk factor survey collected at baseline, and complete demographic and clinical indicator data. Excluded from the analysis were 67 participants with insufficient responses to the dietary food frequency questionnaire (FFQ) and 31 participants with missing body mass index (BMI), 3023 veterans.

Measures

MSCF. The outcome of interest in this study was the MSCF recorded across all participant colonoscopies during the study period. MSCF was categorized as either (1) no neoplasia; (2) < 2 nonadvanced adenomas, including small adenomas (diameter < 10 mm) with tubular histology; or (3) advanced neoplasia (AN), which is characterized by adenomas > 10 mm in diameter, with villous histology, with high-grade dysplasia, or CRC.

Dietary patterns. Dietary pattern scores representing dietary quality and calculated based on recommendations of the US Dietary Guidelines for Americans using the HEI, MD, and DASH diets were independent variables.^26-28 These 3 dietary patterns were chosen for their hypothesized relationship with CRC risk, but each weighs food categories differently (Appendix 1).^22-24,29 Dietary pattern scores were calculated using the CSP #380 self-reported responses to 129 baseline survey questions adapted from a well-established and previously validated semiquantitative FFQ.³⁰ The form was administered by mail twice to a sample of 127 participants at baseline and at 1 year. During this interval, men completed 1-week diet records twice, spaced about 6 months apart. Mean values for intake of most nutrients assessed by the 2 methods were similar. Intraclass correlation coefficients for the baseline and 1-year FFQ-assessed nutrient intakes that ranged from 0.47 for vitamin E (without supplements) to 0.80 for vitamin C (with supplements). Correlation coefficients between the energy-adjusted nutrient intakes were measured by diet records and the 1-year FFQ, which asked about diet during the year encompassing the diet records. Higher raw and percent scores indicated better alignment with recommendations from each respective dietary pattern. Percent scores were calculated as a standardizing method and used in analyses for ease of comparing the dietary patterns. Scoring can be found in Appendix 2.

Demographic characteristics and clinical indicators. Demographic characteristics included age categories, sex, and race/ethnicity. Clinical indicators included BMI, the number of comorbid conditions used to calculate the Charlson Comorbidity Index, family history of CRC in first-degree relatives, number of follow-up colonoscopies across the study period, and food-based vitamin D intake.³¹ These variables were chosen for their applicability found in previous CSP #380 cohort studies.^18,32,33 Self-reported race and ethnicity were collapsed due to small numbers in some groups. The authors acknowledge these are distinct concepts and the variable has limited utility other than for controlling for systemic racism in the model.

Statistical Analyses

Descriptive statistics were used to describe distributional assumptions for all variables, including demographics, clinical indicators, colonoscopy results, and dietary patterns. Pairwise correlations between the total dietary pattern scores and food category scores were calculated with Pearson correlation (r).

Multinomial logistic regression models were created using SAS procedure LOGISTIC with the outcome of the categorical MSCF (no neoplasia, nonadvanced adenoma, or AN).³⁴ A model was created for each independent predictor variable of interest (ie, the HEI, MD, or DASH percentage-standardized dietary pattern score and each food category comprising each dietary pattern score). All models were adjusted for age, sex, race/ethnicity, BMI, number of comorbidities, family history of CRC, number of follow-up colonoscopies, and estimated daily food-derived vitamin D intake. The demographic and clinical indicators were included in the models as they are known to be associated with CRC risk.¹⁸ The number of colonoscopies was included to control for surveillance intensity presuming risk for AN is reduced as polyps are removed. Because colonoscopy findings from an initial screening have unique clinical implications compared with follow- up and surveillance, MSCF was observed in 2 ways in sensitivity analyses: (1) baseline and (2) aggregate follow-up and surveillance only, excluding baseline findings.

Adjusted odds ratios (aORs) and 95% CIs for each of the MSCF outcomes with a reference finding of no neoplasia for the models are presented. We chose not to adjust for multiple comparisons across the different dietary patterns given the correlation between dietary pattern total and category scores but did adjust for multiple comparisons for dietary categories within each dietary pattern. Tests for statistical significance used α= .05 for the dietary pattern total scores and P values for the dietary category scores for each dietary pattern controlled for false discovery rate using the MULTTEST SAS procedure.35 All data manipulations and analyses were performed using SAS version 9.4.

Results

The study included 3023 patients. All were aged 50 to 75 years, 2923 (96.7%) were male and 2532 (83.8%) were non-Hispanic White (Table 1). Most participants were overweight or obese (n = 2535 [83.8%]), 2024 (67.0%) had ≤ 2 comorbidities, and 2602 (86.1%) had no family history of CRC. The MSCF for 1628 patients (53.9%) was no neoplasia, 966 patients (32.0%) was nonadvanced adenoma, and 429 participants (14.2%) had AN.

Mean percent scores were 58.5% for HEI, 38.2% for MD, and 63.1% for the DASH diet, with higher percentages indicating greater alignment with the recommendations for each diet (Table 2). All 3 dietary patterns scores standardized to percentages were strongly and significantly correlated in pairwise comparisons: HEI:MD, r = 0.62 (P < .001); HEI:DASH, r = 0.60 (P < .001); and MD:DASH, r = 0.72 (P < .001). Likewise, food category scores were significantly correlated across dietary patterns. For example, whole grain and fiber values from each dietary score were strongly correlated in pairwise comparisons: HEI Whole Grain:MD Grain, r = 0.64 (P < .001); HEI Whole Grain:DASH Fiber, r = 0.71 (P < .001); and MD Grain:DASH Fiber, r = 0.70 (P < .001).

Associations between individual participants' dietary pattern scores and the outcome of their pooled MSCF from baseline screening and ≥ 10 years of surveillance are presented in Table 3. For each single-point increases in dietary pattern scores (reflecting better dietary quality), aORs for nonadvanced adenoma vs no neoplasia were slightly lower but not statistically significantly: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.98 (95% CI, 0.94-1.02); and DASH, aOR, 0.99 (95% CI, 0.99-1.00). aORs for AN vs no neoplasia were slightly lower for each dietary pattern assessed, and only the MD and DASH scores were significantly different from 1.00: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.95 (95% CI, 0.90-1.00); and DASH, aOR, 0.99 (95% CI, 0.98-1.00).

We observed lower odds for nonadvanced adenoma and AN among all these dietary patterns when there was greater alignment with the recommended intake of whole grains and fiber. In separate models conducted using food categories comprising the dietary patterns as independent variables and after correcting for multiple tests, higher scores for the HEI Refined Grain category were associated with higher odds for nonadvanced adenoma (aOR, 1.03 [95% CI, 1.01-1.05]; P = .01) and AN (aOR, 1.05 [95% CI, 1.02-1.08]; P < .001). Higher scores for the HEI Whole Grain category were associated with lower odds for nonadvanced adenoma (aOR, 0.97 [95% CI, 0.95-0.99]; P = .01) and AN (aOR, 0.96 [95% CI, 0.93-0.99]; P = .01). Higher scores for the MD Grain category were significantly associated with lower odds for nonadvanced adenoma (aOR, 0.44 [95% CI, 0.26-0.75]; P = .002) and AN (aOR, 0.29 [95% CI, 0.14-0.62]; P = .001). The DASH Grains category also was significantly associated with lower odds for AN (aOR, 0.86 [95% CI, 0.78-0.95]; P = .002).

Discussion

In this study of 3023 veterans undergoing first-time screening colonoscopy and ≥ 10 years of surveillance, we found that healthy dietary patterns, as assessed by the MD and DASH diet, were significantly associated with lower risk of AN. Additionally, we identified lower odds for AN and nonadvanced adenoma compared with no neoplasia for higher grain scores for all the dietary patterns studied. Other food categories that comprise the dietary pattern scores had mixed associations with the MSCF outcomes. Several other studies have examined associations between dietary patterns and risk for CRC but to our knowledge, no studies have explored these associations among US veterans.

These results also indicate study participants had better than average (based on a 50% threshold) dietary quality according to the HEI and DASH diet scoring methods we used, but poor dietary quality according to the MD scoring method. The mean HEI scores for the present study were higher than a US Department of Agriculture study by Dong et al that compared dietary quality between veterans and nonveterans using the HEI, for which veterans’ expected HEI score was 45.6 of 100.⁸ This could be explained by the fact that the participants needed to be healthy to be eligible and those with healthier behaviors overall may have self-selected into the study due to motivation for screening during a time when screening was not yet commonplace. ³⁶ Similarly, participants of the present study had higher adherence to the DASH diet (63.1%) than adolescents with diabetes in a study by Günther et al. Conversely, firefighters who were coached to use a Mediterranean-style dietary pattern and dietary had higher adherence to MD than did participants in this study.²⁷

A closer examination of specific food category component scores that comprise the 3 distinct dietary patterns revealed mixed results from the multinomial modeling, which may have to do with the guideline thresholds used to calculate the dietary scores. When analyzed separately in the logistic regression models for their associations with nonadvanced adenomas and AN compared with no neoplasia, higher MD and DASH fruit scores (but not HEI fruit scores) were found to be significant. Other studies have had mixed findings when attempting to test for associations of fruit intake with adenoma recurrence.^10,37

This study had some unexpected findings. Vegetable intake was not associated with nonadvanced adenomas or AN risk. Studies of food categories have consistently found vegetable (specifically cruciferous ones) intake to be linked with lower odds for cancers.³⁸ Likewise, the red meat category, which was only a unique food category in the MD score, was not associated with nonadvanced adenomas or AN. Despite consistent literature suggesting higher intake of red meat and processed meats increases CRC risk, in 2019 the Nutritional Recommendations Consortium indicated that the evidence was weak.^39,40 This study showed higher DASH diet scores for low-fat dairy, which were maximized when participants reported at least 50% of their dairy servings per day as being low-fat, had lower odds for AN. Yet, the MD scores for low-fat dairy had no association with either outcome; their calculation was based on total number of servings per week. This difference in findings suggests the fat intake ratio may be more relevant to CRC risk than intake quantity.

The literature is mixed regarding fatty acid intake and CRC risk, which may be relevant to both dairy and meat intake. One systematic review and meta-analysis found dietary fat and types of fatty acid intake had no association with CRC risk.⁴¹ However, a more recent meta-analysis that assessed both dietary intake and plasma levels of fatty acids did find some statistically significant differences for various types of fatty acids and CRC risk.⁴²

The findings in the present study that grain intake is associated with lower odds for more severe colonoscopy findings among veterans are notable.⁴³ Lieberman et al, using the CSP #380 data, found that cereal fiber intake was associated with a lower odds for AN compared with hyperplastic polyps (OR, 0.98 [95% CI, 0.96- 1.00]).¹⁸ Similarly, Hullings et al determined that older adults in the highest quintile of cereal fiber intake had significantly lower odds of CRC than those in lower odds for CRC when compared with lowest quintile (OR, 0.89 [95% CI, 0.83- 0.96]; P < .001).⁴⁴ These findings support existing guidance that prioritizes whole grains as a key source of dietary fiber for CRC prevention.

A recent literature review on fiber, fat, and CRC risk suggested a consensus regarding one protective mechanism: dietary fiber from grains modulates the gut microbiota by promoting butyrate synthesis.⁴⁵ Butyrate is a short-chain fatty acid that supports energy production in colonocytes and has tumor-suppressing properties.⁴⁶ Our findings suggest there could be more to learn about the relationship between butyrate production and reduction of CRC risk through metabolomic studies that use measurements of plasma butyrate. These studies may examine associations between not just a singular food or food category, but rather food patterns that include fruits, vegetables, nuts and seeds, and whole grains known to promote butyrate production and plasma butyrate.⁴⁷

Improved understanding of mechanisms and risk-modifying lifestyle factors such as dietary patterns may enhance prevention strategies. Identifying the collective chemopreventive characteristics of a specific dietary pattern (eg, MD) will be helpful to clinicians and health care staff to promote healthy eating to reduce cancer risk. More studies are needed to understand whether such promotion is more clinically applicable and effective for patients, as compared with eating more or less of specific foods (eg, more whole grains, less red meat). Furthermore, considering important environmental factors collectively beyond dietary patterns may offer a way to better tailor screening and implement a variety of lifestyle interventions. In the literature, this is often referred to as a teachable moment when patients’ attentions are captured and may position them to be more receptive to guidance.⁴⁸

Limitations

This study has several important limitations and leaves opportunities for future studies that explore the role of dietary patterns and AN or CRC risk. First, the FFQ data used to calculate dietary pattern scores used in analysis were only captured at baseline, and there are nearly 3 decades across the study period. However, it is widely assumed that the diets of older adults, like those included in this study, remain stable over time which is appropriate given our sample population was aged 50 to 75 years when the baseline FFQ data were collected.^49-51 Additionally, while the HEI is a well-documented, standard scoring method for dietary quality, there are multitudes of dietary pattern scoring approaches for MD and DASH.^23,52,53 Finally, findings from this study using the sample of veterans may not be generalizable to a broader population. Future longitudinal studies that test for a clinically significant change threshold are warranted.

Conclusion

Results of this study suggest future research should further explore the effects of dietary patterns, particularly intake of specific food groups in combination, as opposed to individual nutrients or food items, on AN and CRC risk. Possible studies might explore these dietary patterns for their mechanistic role in altering the microbiome metabolism, which may influence CRC outcomes or include diet in a more comprehensive, holistic risk score that could be used to predict colonic neoplasia risk or in intervention studies that assess the effects of dietary changes on long-term CRC prevention. We suggest there are differences in people’s dietary intake patterns that might be important to consider when implementing tailored approaches to CRC risk mitigation.

Screening for colorectal cancer (CRC) with colonoscopy enables the identification and removal of CRC precursors (colonic adenomas) and has been associated with reduced risk of CRC incidence and mortality.^1-3 Furthermore, there is consensus that diet and lifestyle may be associated with forestalling CRC pathogenesis at the intermediate adenoma stages.^4-7 However, studies have shown that US veterans have poorer diet quality and a higher risk for neoplasia compared with nonveterans, reinforcing the need for tailored clinical approaches.^8,9 Combining screening with conversations about modifiable environmental and lifestyle risk factors, such as poor diet, is a highly relevant and possibly easily leveraged prevention for those at high risk. However, there is limited evidence for any particular dietary patterns or dietary features that are most important over time.⁷

Several dietary components have been shown to be associated with CRC risk,10 either as potentially chemopreventive (fiber, fruits and vegetables,¹¹ dairy,¹² supplemental vitamin D,¹³ calcium,¹⁴ and multivitamins¹⁵) or carcinogenic (red meat¹⁶ and alcohol¹⁷). Previous studies of veterans have similarly shown that higher intake of fiber and vitamin D reduced risk, and red meat is associated with an increased risk for finding CRC precursors during colonoscopy.¹⁸ However, these dietary categories are often analyzed in isolation. Studying healthy dietary patterns in aggregate may be more clinically relevant and easier to implement for prevention of CRC and its precursors.^19-21 Healthy dietary patterns, such as the US Dietary Guidelines for Americans represented by the Healthy Eating Index (HEI), the Mediterranean diet (MD), and the Dietary Approaches to Stop Hypertension (DASH) diet, have been associated with lower risk for chronic disease.^22-24 Despite the extant literature, no known studies have compared these dietary patterns for associations with risk of CRC precursor or CRC development among US veterans undergoing long-term screening and follow-up after a baseline colonoscopy.

The objective of this study was to test for associations between baseline scores of healthy dietary patterns and the most severe colonoscopy findings (MSCFs) over ≥ 10 years following a baseline screening colonoscopy in veterans.

Methods

Participants in the Cooperative Studies Program (CSP) #380 cohort study included 3121 asymptomatic veterans aged 50 to 75 years at baseline who had consented to initial screening colonoscopy between 1994 and 1997, with subsequent follow-up and surveillance.²⁵ Prior to their colonoscopy, all participants completed a baseline study survey that included questions about cancer risk factors including family history of CRC, diet, physical activity, and medication use.

Included in this cross-sectional analysis were data from a sample of veteran participants of the CSP #380 cohort with 1 baseline colonoscopy, follow-up surveillance through 2009, a cancer risk factor survey collected at baseline, and complete demographic and clinical indicator data. Excluded from the analysis were 67 participants with insufficient responses to the dietary food frequency questionnaire (FFQ) and 31 participants with missing body mass index (BMI), 3023 veterans.

Measures

MSCF. The outcome of interest in this study was the MSCF recorded across all participant colonoscopies during the study period. MSCF was categorized as either (1) no neoplasia; (2) < 2 nonadvanced adenomas, including small adenomas (diameter < 10 mm) with tubular histology; or (3) advanced neoplasia (AN), which is characterized by adenomas > 10 mm in diameter, with villous histology, with high-grade dysplasia, or CRC.

Dietary patterns. Dietary pattern scores representing dietary quality and calculated based on recommendations of the US Dietary Guidelines for Americans using the HEI, MD, and DASH diets were independent variables.^26-28 These 3 dietary patterns were chosen for their hypothesized relationship with CRC risk, but each weighs food categories differently (Appendix 1).^22-24,29 Dietary pattern scores were calculated using the CSP #380 self-reported responses to 129 baseline survey questions adapted from a well-established and previously validated semiquantitative FFQ.³⁰ The form was administered by mail twice to a sample of 127 participants at baseline and at 1 year. During this interval, men completed 1-week diet records twice, spaced about 6 months apart. Mean values for intake of most nutrients assessed by the 2 methods were similar. Intraclass correlation coefficients for the baseline and 1-year FFQ-assessed nutrient intakes that ranged from 0.47 for vitamin E (without supplements) to 0.80 for vitamin C (with supplements). Correlation coefficients between the energy-adjusted nutrient intakes were measured by diet records and the 1-year FFQ, which asked about diet during the year encompassing the diet records. Higher raw and percent scores indicated better alignment with recommendations from each respective dietary pattern. Percent scores were calculated as a standardizing method and used in analyses for ease of comparing the dietary patterns. Scoring can be found in Appendix 2.

Demographic characteristics and clinical indicators. Demographic characteristics included age categories, sex, and race/ethnicity. Clinical indicators included BMI, the number of comorbid conditions used to calculate the Charlson Comorbidity Index, family history of CRC in first-degree relatives, number of follow-up colonoscopies across the study period, and food-based vitamin D intake.³¹ These variables were chosen for their applicability found in previous CSP #380 cohort studies.^18,32,33 Self-reported race and ethnicity were collapsed due to small numbers in some groups. The authors acknowledge these are distinct concepts and the variable has limited utility other than for controlling for systemic racism in the model.

Statistical Analyses

Descriptive statistics were used to describe distributional assumptions for all variables, including demographics, clinical indicators, colonoscopy results, and dietary patterns. Pairwise correlations between the total dietary pattern scores and food category scores were calculated with Pearson correlation (r).

Multinomial logistic regression models were created using SAS procedure LOGISTIC with the outcome of the categorical MSCF (no neoplasia, nonadvanced adenoma, or AN).³⁴ A model was created for each independent predictor variable of interest (ie, the HEI, MD, or DASH percentage-standardized dietary pattern score and each food category comprising each dietary pattern score). All models were adjusted for age, sex, race/ethnicity, BMI, number of comorbidities, family history of CRC, number of follow-up colonoscopies, and estimated daily food-derived vitamin D intake. The demographic and clinical indicators were included in the models as they are known to be associated with CRC risk.¹⁸ The number of colonoscopies was included to control for surveillance intensity presuming risk for AN is reduced as polyps are removed. Because colonoscopy findings from an initial screening have unique clinical implications compared with follow- up and surveillance, MSCF was observed in 2 ways in sensitivity analyses: (1) baseline and (2) aggregate follow-up and surveillance only, excluding baseline findings.

Adjusted odds ratios (aORs) and 95% CIs for each of the MSCF outcomes with a reference finding of no neoplasia for the models are presented. We chose not to adjust for multiple comparisons across the different dietary patterns given the correlation between dietary pattern total and category scores but did adjust for multiple comparisons for dietary categories within each dietary pattern. Tests for statistical significance used α= .05 for the dietary pattern total scores and P values for the dietary category scores for each dietary pattern controlled for false discovery rate using the MULTTEST SAS procedure.35 All data manipulations and analyses were performed using SAS version 9.4.

Results

The study included 3023 patients. All were aged 50 to 75 years, 2923 (96.7%) were male and 2532 (83.8%) were non-Hispanic White (Table 1). Most participants were overweight or obese (n = 2535 [83.8%]), 2024 (67.0%) had ≤ 2 comorbidities, and 2602 (86.1%) had no family history of CRC. The MSCF for 1628 patients (53.9%) was no neoplasia, 966 patients (32.0%) was nonadvanced adenoma, and 429 participants (14.2%) had AN.

Mean percent scores were 58.5% for HEI, 38.2% for MD, and 63.1% for the DASH diet, with higher percentages indicating greater alignment with the recommendations for each diet (Table 2). All 3 dietary patterns scores standardized to percentages were strongly and significantly correlated in pairwise comparisons: HEI:MD, r = 0.62 (P < .001); HEI:DASH, r = 0.60 (P < .001); and MD:DASH, r = 0.72 (P < .001). Likewise, food category scores were significantly correlated across dietary patterns. For example, whole grain and fiber values from each dietary score were strongly correlated in pairwise comparisons: HEI Whole Grain:MD Grain, r = 0.64 (P < .001); HEI Whole Grain:DASH Fiber, r = 0.71 (P < .001); and MD Grain:DASH Fiber, r = 0.70 (P < .001).

Associations between individual participants' dietary pattern scores and the outcome of their pooled MSCF from baseline screening and ≥ 10 years of surveillance are presented in Table 3. For each single-point increases in dietary pattern scores (reflecting better dietary quality), aORs for nonadvanced adenoma vs no neoplasia were slightly lower but not statistically significantly: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.98 (95% CI, 0.94-1.02); and DASH, aOR, 0.99 (95% CI, 0.99-1.00). aORs for AN vs no neoplasia were slightly lower for each dietary pattern assessed, and only the MD and DASH scores were significantly different from 1.00: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.95 (95% CI, 0.90-1.00); and DASH, aOR, 0.99 (95% CI, 0.98-1.00).

We observed lower odds for nonadvanced adenoma and AN among all these dietary patterns when there was greater alignment with the recommended intake of whole grains and fiber. In separate models conducted using food categories comprising the dietary patterns as independent variables and after correcting for multiple tests, higher scores for the HEI Refined Grain category were associated with higher odds for nonadvanced adenoma (aOR, 1.03 [95% CI, 1.01-1.05]; P = .01) and AN (aOR, 1.05 [95% CI, 1.02-1.08]; P < .001). Higher scores for the HEI Whole Grain category were associated with lower odds for nonadvanced adenoma (aOR, 0.97 [95% CI, 0.95-0.99]; P = .01) and AN (aOR, 0.96 [95% CI, 0.93-0.99]; P = .01). Higher scores for the MD Grain category were significantly associated with lower odds for nonadvanced adenoma (aOR, 0.44 [95% CI, 0.26-0.75]; P = .002) and AN (aOR, 0.29 [95% CI, 0.14-0.62]; P = .001). The DASH Grains category also was significantly associated with lower odds for AN (aOR, 0.86 [95% CI, 0.78-0.95]; P = .002).

Discussion

In this study of 3023 veterans undergoing first-time screening colonoscopy and ≥ 10 years of surveillance, we found that healthy dietary patterns, as assessed by the MD and DASH diet, were significantly associated with lower risk of AN. Additionally, we identified lower odds for AN and nonadvanced adenoma compared with no neoplasia for higher grain scores for all the dietary patterns studied. Other food categories that comprise the dietary pattern scores had mixed associations with the MSCF outcomes. Several other studies have examined associations between dietary patterns and risk for CRC but to our knowledge, no studies have explored these associations among US veterans.

These results also indicate study participants had better than average (based on a 50% threshold) dietary quality according to the HEI and DASH diet scoring methods we used, but poor dietary quality according to the MD scoring method. The mean HEI scores for the present study were higher than a US Department of Agriculture study by Dong et al that compared dietary quality between veterans and nonveterans using the HEI, for which veterans’ expected HEI score was 45.6 of 100.⁸ This could be explained by the fact that the participants needed to be healthy to be eligible and those with healthier behaviors overall may have self-selected into the study due to motivation for screening during a time when screening was not yet commonplace. ³⁶ Similarly, participants of the present study had higher adherence to the DASH diet (63.1%) than adolescents with diabetes in a study by Günther et al. Conversely, firefighters who were coached to use a Mediterranean-style dietary pattern and dietary had higher adherence to MD than did participants in this study.²⁷

A closer examination of specific food category component scores that comprise the 3 distinct dietary patterns revealed mixed results from the multinomial modeling, which may have to do with the guideline thresholds used to calculate the dietary scores. When analyzed separately in the logistic regression models for their associations with nonadvanced adenomas and AN compared with no neoplasia, higher MD and DASH fruit scores (but not HEI fruit scores) were found to be significant. Other studies have had mixed findings when attempting to test for associations of fruit intake with adenoma recurrence.^10,37

This study had some unexpected findings. Vegetable intake was not associated with nonadvanced adenomas or AN risk. Studies of food categories have consistently found vegetable (specifically cruciferous ones) intake to be linked with lower odds for cancers.³⁸ Likewise, the red meat category, which was only a unique food category in the MD score, was not associated with nonadvanced adenomas or AN. Despite consistent literature suggesting higher intake of red meat and processed meats increases CRC risk, in 2019 the Nutritional Recommendations Consortium indicated that the evidence was weak.^39,40 This study showed higher DASH diet scores for low-fat dairy, which were maximized when participants reported at least 50% of their dairy servings per day as being low-fat, had lower odds for AN. Yet, the MD scores for low-fat dairy had no association with either outcome; their calculation was based on total number of servings per week. This difference in findings suggests the fat intake ratio may be more relevant to CRC risk than intake quantity.

The literature is mixed regarding fatty acid intake and CRC risk, which may be relevant to both dairy and meat intake. One systematic review and meta-analysis found dietary fat and types of fatty acid intake had no association with CRC risk.⁴¹ However, a more recent meta-analysis that assessed both dietary intake and plasma levels of fatty acids did find some statistically significant differences for various types of fatty acids and CRC risk.⁴²

The findings in the present study that grain intake is associated with lower odds for more severe colonoscopy findings among veterans are notable.⁴³ Lieberman et al, using the CSP #380 data, found that cereal fiber intake was associated with a lower odds for AN compared with hyperplastic polyps (OR, 0.98 [95% CI, 0.96- 1.00]).¹⁸ Similarly, Hullings et al determined that older adults in the highest quintile of cereal fiber intake had significantly lower odds of CRC than those in lower odds for CRC when compared with lowest quintile (OR, 0.89 [95% CI, 0.83- 0.96]; P < .001).⁴⁴ These findings support existing guidance that prioritizes whole grains as a key source of dietary fiber for CRC prevention.

A recent literature review on fiber, fat, and CRC risk suggested a consensus regarding one protective mechanism: dietary fiber from grains modulates the gut microbiota by promoting butyrate synthesis.⁴⁵ Butyrate is a short-chain fatty acid that supports energy production in colonocytes and has tumor-suppressing properties.⁴⁶ Our findings suggest there could be more to learn about the relationship between butyrate production and reduction of CRC risk through metabolomic studies that use measurements of plasma butyrate. These studies may examine associations between not just a singular food or food category, but rather food patterns that include fruits, vegetables, nuts and seeds, and whole grains known to promote butyrate production and plasma butyrate.⁴⁷

Improved understanding of mechanisms and risk-modifying lifestyle factors such as dietary patterns may enhance prevention strategies. Identifying the collective chemopreventive characteristics of a specific dietary pattern (eg, MD) will be helpful to clinicians and health care staff to promote healthy eating to reduce cancer risk. More studies are needed to understand whether such promotion is more clinically applicable and effective for patients, as compared with eating more or less of specific foods (eg, more whole grains, less red meat). Furthermore, considering important environmental factors collectively beyond dietary patterns may offer a way to better tailor screening and implement a variety of lifestyle interventions. In the literature, this is often referred to as a teachable moment when patients’ attentions are captured and may position them to be more receptive to guidance.⁴⁸

Limitations

This study has several important limitations and leaves opportunities for future studies that explore the role of dietary patterns and AN or CRC risk. First, the FFQ data used to calculate dietary pattern scores used in analysis were only captured at baseline, and there are nearly 3 decades across the study period. However, it is widely assumed that the diets of older adults, like those included in this study, remain stable over time which is appropriate given our sample population was aged 50 to 75 years when the baseline FFQ data were collected.^49-51 Additionally, while the HEI is a well-documented, standard scoring method for dietary quality, there are multitudes of dietary pattern scoring approaches for MD and DASH.^23,52,53 Finally, findings from this study using the sample of veterans may not be generalizable to a broader population. Future longitudinal studies that test for a clinically significant change threshold are warranted.

Conclusion

Results of this study suggest future research should further explore the effects of dietary patterns, particularly intake of specific food groups in combination, as opposed to individual nutrients or food items, on AN and CRC risk. Possible studies might explore these dietary patterns for their mechanistic role in altering the microbiome metabolism, which may influence CRC outcomes or include diet in a more comprehensive, holistic risk score that could be used to predict colonic neoplasia risk or in intervention studies that assess the effects of dietary changes on long-term CRC prevention. We suggest there are differences in people’s dietary intake patterns that might be important to consider when implementing tailored approaches to CRC risk mitigation.

Screening for colorectal cancer (CRC) with colonoscopy enables the identification and removal of CRC precursors (colonic adenomas) and has been associated with reduced risk of CRC incidence and mortality.^1-3 Furthermore, there is consensus that diet and lifestyle may be associated with forestalling CRC pathogenesis at the intermediate adenoma stages.^4-7 However, studies have shown that US veterans have poorer diet quality and a higher risk for neoplasia compared with nonveterans, reinforcing the need for tailored clinical approaches.^8,9 Combining screening with conversations about modifiable environmental and lifestyle risk factors, such as poor diet, is a highly relevant and possibly easily leveraged prevention for those at high risk. However, there is limited evidence for any particular dietary patterns or dietary features that are most important over time.⁷

Several dietary components have been shown to be associated with CRC risk,10 either as potentially chemopreventive (fiber, fruits and vegetables,¹¹ dairy,¹² supplemental vitamin D,¹³ calcium,¹⁴ and multivitamins¹⁵) or carcinogenic (red meat¹⁶ and alcohol¹⁷). Previous studies of veterans have similarly shown that higher intake of fiber and vitamin D reduced risk, and red meat is associated with an increased risk for finding CRC precursors during colonoscopy.¹⁸ However, these dietary categories are often analyzed in isolation. Studying healthy dietary patterns in aggregate may be more clinically relevant and easier to implement for prevention of CRC and its precursors.^19-21 Healthy dietary patterns, such as the US Dietary Guidelines for Americans represented by the Healthy Eating Index (HEI), the Mediterranean diet (MD), and the Dietary Approaches to Stop Hypertension (DASH) diet, have been associated with lower risk for chronic disease.^22-24 Despite the extant literature, no known studies have compared these dietary patterns for associations with risk of CRC precursor or CRC development among US veterans undergoing long-term screening and follow-up after a baseline colonoscopy.

The objective of this study was to test for associations between baseline scores of healthy dietary patterns and the most severe colonoscopy findings (MSCFs) over ≥ 10 years following a baseline screening colonoscopy in veterans.

Methods

Participants in the Cooperative Studies Program (CSP) #380 cohort study included 3121 asymptomatic veterans aged 50 to 75 years at baseline who had consented to initial screening colonoscopy between 1994 and 1997, with subsequent follow-up and surveillance.²⁵ Prior to their colonoscopy, all participants completed a baseline study survey that included questions about cancer risk factors including family history of CRC, diet, physical activity, and medication use.

Included in this cross-sectional analysis were data from a sample of veteran participants of the CSP #380 cohort with 1 baseline colonoscopy, follow-up surveillance through 2009, a cancer risk factor survey collected at baseline, and complete demographic and clinical indicator data. Excluded from the analysis were 67 participants with insufficient responses to the dietary food frequency questionnaire (FFQ) and 31 participants with missing body mass index (BMI), 3023 veterans.

Measures

MSCF. The outcome of interest in this study was the MSCF recorded across all participant colonoscopies during the study period. MSCF was categorized as either (1) no neoplasia; (2) < 2 nonadvanced adenomas, including small adenomas (diameter < 10 mm) with tubular histology; or (3) advanced neoplasia (AN), which is characterized by adenomas > 10 mm in diameter, with villous histology, with high-grade dysplasia, or CRC.

Dietary patterns. Dietary pattern scores representing dietary quality and calculated based on recommendations of the US Dietary Guidelines for Americans using the HEI, MD, and DASH diets were independent variables.^26-28 These 3 dietary patterns were chosen for their hypothesized relationship with CRC risk, but each weighs food categories differently (Appendix 1).^22-24,29 Dietary pattern scores were calculated using the CSP #380 self-reported responses to 129 baseline survey questions adapted from a well-established and previously validated semiquantitative FFQ.³⁰ The form was administered by mail twice to a sample of 127 participants at baseline and at 1 year. During this interval, men completed 1-week diet records twice, spaced about 6 months apart. Mean values for intake of most nutrients assessed by the 2 methods were similar. Intraclass correlation coefficients for the baseline and 1-year FFQ-assessed nutrient intakes that ranged from 0.47 for vitamin E (without supplements) to 0.80 for vitamin C (with supplements). Correlation coefficients between the energy-adjusted nutrient intakes were measured by diet records and the 1-year FFQ, which asked about diet during the year encompassing the diet records. Higher raw and percent scores indicated better alignment with recommendations from each respective dietary pattern. Percent scores were calculated as a standardizing method and used in analyses for ease of comparing the dietary patterns. Scoring can be found in Appendix 2.

Demographic characteristics and clinical indicators. Demographic characteristics included age categories, sex, and race/ethnicity. Clinical indicators included BMI, the number of comorbid conditions used to calculate the Charlson Comorbidity Index, family history of CRC in first-degree relatives, number of follow-up colonoscopies across the study period, and food-based vitamin D intake.³¹ These variables were chosen for their applicability found in previous CSP #380 cohort studies.^18,32,33 Self-reported race and ethnicity were collapsed due to small numbers in some groups. The authors acknowledge these are distinct concepts and the variable has limited utility other than for controlling for systemic racism in the model.

Statistical Analyses

Descriptive statistics were used to describe distributional assumptions for all variables, including demographics, clinical indicators, colonoscopy results, and dietary patterns. Pairwise correlations between the total dietary pattern scores and food category scores were calculated with Pearson correlation (r).

Multinomial logistic regression models were created using SAS procedure LOGISTIC with the outcome of the categorical MSCF (no neoplasia, nonadvanced adenoma, or AN).³⁴ A model was created for each independent predictor variable of interest (ie, the HEI, MD, or DASH percentage-standardized dietary pattern score and each food category comprising each dietary pattern score). All models were adjusted for age, sex, race/ethnicity, BMI, number of comorbidities, family history of CRC, number of follow-up colonoscopies, and estimated daily food-derived vitamin D intake. The demographic and clinical indicators were included in the models as they are known to be associated with CRC risk.¹⁸ The number of colonoscopies was included to control for surveillance intensity presuming risk for AN is reduced as polyps are removed. Because colonoscopy findings from an initial screening have unique clinical implications compared with follow- up and surveillance, MSCF was observed in 2 ways in sensitivity analyses: (1) baseline and (2) aggregate follow-up and surveillance only, excluding baseline findings.

Adjusted odds ratios (aORs) and 95% CIs for each of the MSCF outcomes with a reference finding of no neoplasia for the models are presented. We chose not to adjust for multiple comparisons across the different dietary patterns given the correlation between dietary pattern total and category scores but did adjust for multiple comparisons for dietary categories within each dietary pattern. Tests for statistical significance used α= .05 for the dietary pattern total scores and P values for the dietary category scores for each dietary pattern controlled for false discovery rate using the MULTTEST SAS procedure.35 All data manipulations and analyses were performed using SAS version 9.4.

Results

The study included 3023 patients. All were aged 50 to 75 years, 2923 (96.7%) were male and 2532 (83.8%) were non-Hispanic White (Table 1). Most participants were overweight or obese (n = 2535 [83.8%]), 2024 (67.0%) had ≤ 2 comorbidities, and 2602 (86.1%) had no family history of CRC. The MSCF for 1628 patients (53.9%) was no neoplasia, 966 patients (32.0%) was nonadvanced adenoma, and 429 participants (14.2%) had AN.

Mean percent scores were 58.5% for HEI, 38.2% for MD, and 63.1% for the DASH diet, with higher percentages indicating greater alignment with the recommendations for each diet (Table 2). All 3 dietary patterns scores standardized to percentages were strongly and significantly correlated in pairwise comparisons: HEI:MD, r = 0.62 (P < .001); HEI:DASH, r = 0.60 (P < .001); and MD:DASH, r = 0.72 (P < .001). Likewise, food category scores were significantly correlated across dietary patterns. For example, whole grain and fiber values from each dietary score were strongly correlated in pairwise comparisons: HEI Whole Grain:MD Grain, r = 0.64 (P < .001); HEI Whole Grain:DASH Fiber, r = 0.71 (P < .001); and MD Grain:DASH Fiber, r = 0.70 (P < .001).

Associations between individual participants' dietary pattern scores and the outcome of their pooled MSCF from baseline screening and ≥ 10 years of surveillance are presented in Table 3. For each single-point increases in dietary pattern scores (reflecting better dietary quality), aORs for nonadvanced adenoma vs no neoplasia were slightly lower but not statistically significantly: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.98 (95% CI, 0.94-1.02); and DASH, aOR, 0.99 (95% CI, 0.99-1.00). aORs for AN vs no neoplasia were slightly lower for each dietary pattern assessed, and only the MD and DASH scores were significantly different from 1.00: HEI, aOR, 1.00 (95% CI, 0.99-1.01); MD, aOR, 0.95 (95% CI, 0.90-1.00); and DASH, aOR, 0.99 (95% CI, 0.98-1.00).

We observed lower odds for nonadvanced adenoma and AN among all these dietary patterns when there was greater alignment with the recommended intake of whole grains and fiber. In separate models conducted using food categories comprising the dietary patterns as independent variables and after correcting for multiple tests, higher scores for the HEI Refined Grain category were associated with higher odds for nonadvanced adenoma (aOR, 1.03 [95% CI, 1.01-1.05]; P = .01) and AN (aOR, 1.05 [95% CI, 1.02-1.08]; P < .001). Higher scores for the HEI Whole Grain category were associated with lower odds for nonadvanced adenoma (aOR, 0.97 [95% CI, 0.95-0.99]; P = .01) and AN (aOR, 0.96 [95% CI, 0.93-0.99]; P = .01). Higher scores for the MD Grain category were significantly associated with lower odds for nonadvanced adenoma (aOR, 0.44 [95% CI, 0.26-0.75]; P = .002) and AN (aOR, 0.29 [95% CI, 0.14-0.62]; P = .001). The DASH Grains category also was significantly associated with lower odds for AN (aOR, 0.86 [95% CI, 0.78-0.95]; P = .002).

Discussion

In this study of 3023 veterans undergoing first-time screening colonoscopy and ≥ 10 years of surveillance, we found that healthy dietary patterns, as assessed by the MD and DASH diet, were significantly associated with lower risk of AN. Additionally, we identified lower odds for AN and nonadvanced adenoma compared with no neoplasia for higher grain scores for all the dietary patterns studied. Other food categories that comprise the dietary pattern scores had mixed associations with the MSCF outcomes. Several other studies have examined associations between dietary patterns and risk for CRC but to our knowledge, no studies have explored these associations among US veterans.

These results also indicate study participants had better than average (based on a 50% threshold) dietary quality according to the HEI and DASH diet scoring methods we used, but poor dietary quality according to the MD scoring method. The mean HEI scores for the present study were higher than a US Department of Agriculture study by Dong et al that compared dietary quality between veterans and nonveterans using the HEI, for which veterans’ expected HEI score was 45.6 of 100.⁸ This could be explained by the fact that the participants needed to be healthy to be eligible and those with healthier behaviors overall may have self-selected into the study due to motivation for screening during a time when screening was not yet commonplace. ³⁶ Similarly, participants of the present study had higher adherence to the DASH diet (63.1%) than adolescents with diabetes in a study by Günther et al. Conversely, firefighters who were coached to use a Mediterranean-style dietary pattern and dietary had higher adherence to MD than did participants in this study.²⁷

A closer examination of specific food category component scores that comprise the 3 distinct dietary patterns revealed mixed results from the multinomial modeling, which may have to do with the guideline thresholds used to calculate the dietary scores. When analyzed separately in the logistic regression models for their associations with nonadvanced adenomas and AN compared with no neoplasia, higher MD and DASH fruit scores (but not HEI fruit scores) were found to be significant. Other studies have had mixed findings when attempting to test for associations of fruit intake with adenoma recurrence.^10,37

This study had some unexpected findings. Vegetable intake was not associated with nonadvanced adenomas or AN risk. Studies of food categories have consistently found vegetable (specifically cruciferous ones) intake to be linked with lower odds for cancers.³⁸ Likewise, the red meat category, which was only a unique food category in the MD score, was not associated with nonadvanced adenomas or AN. Despite consistent literature suggesting higher intake of red meat and processed meats increases CRC risk, in 2019 the Nutritional Recommendations Consortium indicated that the evidence was weak.^39,40 This study showed higher DASH diet scores for low-fat dairy, which were maximized when participants reported at least 50% of their dairy servings per day as being low-fat, had lower odds for AN. Yet, the MD scores for low-fat dairy had no association with either outcome; their calculation was based on total number of servings per week. This difference in findings suggests the fat intake ratio may be more relevant to CRC risk than intake quantity.

The literature is mixed regarding fatty acid intake and CRC risk, which may be relevant to both dairy and meat intake. One systematic review and meta-analysis found dietary fat and types of fatty acid intake had no association with CRC risk.⁴¹ However, a more recent meta-analysis that assessed both dietary intake and plasma levels of fatty acids did find some statistically significant differences for various types of fatty acids and CRC risk.⁴²

The findings in the present study that grain intake is associated with lower odds for more severe colonoscopy findings among veterans are notable.⁴³ Lieberman et al, using the CSP #380 data, found that cereal fiber intake was associated with a lower odds for AN compared with hyperplastic polyps (OR, 0.98 [95% CI, 0.96- 1.00]).¹⁸ Similarly, Hullings et al determined that older adults in the highest quintile of cereal fiber intake had significantly lower odds of CRC than those in lower odds for CRC when compared with lowest quintile (OR, 0.89 [95% CI, 0.83- 0.96]; P < .001).⁴⁴ These findings support existing guidance that prioritizes whole grains as a key source of dietary fiber for CRC prevention.

A recent literature review on fiber, fat, and CRC risk suggested a consensus regarding one protective mechanism: dietary fiber from grains modulates the gut microbiota by promoting butyrate synthesis.⁴⁵ Butyrate is a short-chain fatty acid that supports energy production in colonocytes and has tumor-suppressing properties.⁴⁶ Our findings suggest there could be more to learn about the relationship between butyrate production and reduction of CRC risk through metabolomic studies that use measurements of plasma butyrate. These studies may examine associations between not just a singular food or food category, but rather food patterns that include fruits, vegetables, nuts and seeds, and whole grains known to promote butyrate production and plasma butyrate.⁴⁷

Improved understanding of mechanisms and risk-modifying lifestyle factors such as dietary patterns may enhance prevention strategies. Identifying the collective chemopreventive characteristics of a specific dietary pattern (eg, MD) will be helpful to clinicians and health care staff to promote healthy eating to reduce cancer risk. More studies are needed to understand whether such promotion is more clinically applicable and effective for patients, as compared with eating more or less of specific foods (eg, more whole grains, less red meat). Furthermore, considering important environmental factors collectively beyond dietary patterns may offer a way to better tailor screening and implement a variety of lifestyle interventions. In the literature, this is often referred to as a teachable moment when patients’ attentions are captured and may position them to be more receptive to guidance.⁴⁸

Limitations

This study has several important limitations and leaves opportunities for future studies that explore the role of dietary patterns and AN or CRC risk. First, the FFQ data used to calculate dietary pattern scores used in analysis were only captured at baseline, and there are nearly 3 decades across the study period. However, it is widely assumed that the diets of older adults, like those included in this study, remain stable over time which is appropriate given our sample population was aged 50 to 75 years when the baseline FFQ data were collected.^49-51 Additionally, while the HEI is a well-documented, standard scoring method for dietary quality, there are multitudes of dietary pattern scoring approaches for MD and DASH.^23,52,53 Finally, findings from this study using the sample of veterans may not be generalizable to a broader population. Future longitudinal studies that test for a clinically significant change threshold are warranted.

Conclusion

Results of this study suggest future research should further explore the effects of dietary patterns, particularly intake of specific food groups in combination, as opposed to individual nutrients or food items, on AN and CRC risk. Possible studies might explore these dietary patterns for their mechanistic role in altering the microbiome metabolism, which may influence CRC outcomes or include diet in a more comprehensive, holistic risk score that could be used to predict colonic neoplasia risk or in intervention studies that assess the effects of dietary changes on long-term CRC prevention. We suggest there are differences in people’s dietary intake patterns that might be important to consider when implementing tailored approaches to CRC risk mitigation.

PHILADELPHIA — Artificial intelligence–assisted colonoscopy (AIAC) with computer-aided detection (CADe) technology may improve adenoma detection rate (ADR), but it’s also associated with higher detection and removal of non-neoplastic lesions, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.

University of Minnesota

“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.

In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.

In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.

Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.

In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.

Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.

More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”

“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.

Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.

Valley Medical Group

Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey. 

“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”

The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

PHILADELPHIA — Artificial intelligence–assisted colonoscopy (AIAC) with computer-aided detection (CADe) technology may improve adenoma detection rate (ADR), but it’s also associated with higher detection and removal of non-neoplastic lesions, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.

University of Minnesota

“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.

In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.

In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.

Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.

In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.

Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.

More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”

“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.

Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.

Valley Medical Group

Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey. 

“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”

The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

PHILADELPHIA — Artificial intelligence–assisted colonoscopy (AIAC) with computer-aided detection (CADe) technology may improve adenoma detection rate (ADR), but it’s also associated with higher detection and removal of non-neoplastic lesions, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

In particular, AIAC led to a statistically and clinically significant increase in the proportion of exams that detected lesions that after resection were all found to be benign, compared with unassisted colonoscopy.

University of Minnesota

“The potential implications include increased procedural risks, as well as costs, such as pathology costs and other healthcare expenditures, without any additional colorectal cancer prevention benefit,” said lead author Tessa Herman, MD, chief resident of internal medicine at the University of Minnesota, Minneapolis, and Minneapolis Veterans Affairs Health Care System.

In a previous implementation trial at the Minneapolis VA Medical Center, Herman and colleagues compared ADR between a group of patients undergoing AIAC and a historical cohort of patients who had non–AI-assisted colonoscopy.

In this subsequent study, the research team conducted an ad hoc analysis of data from the previous trial to determine the proportion of colonoscopies for screening, surveillance, and positive fecal immunochemical tests which detect lesions that after resection are all found to be benign. They excluded colonoscopies conducted for diagnostic indications or inflammatory bowel disease, as well as incomplete colonoscopies, and for those with inadequate bowel preparation.

Overall, they studied 441 non-AIAC colonoscopies (between November 2022 and April 2023) and 599 AIAC colonoscopies (between May 2023 and October 2023). The groups were balanced, and there were no significant differences in patient demographics, endoscopists, AI technology, procedure time, or average number of polyps detected.

In the non-AIAC cohort, 37 cases (8.4%) had polypectomies that revealed only benign lesions, as compared with 74 cases (12.4%) in the AIAC cohort. The most common resected lesions were benign colonic mucosa, lymphoid aggregates, and hyperplastic polyps.

Applied to the 15 million colonoscopies conducted in the United States per year, the findings indicate that full adoption of AIAC could result in about 600,000 more colonoscopies in which only benign, nonadenomatous lesions are removed, compared with traditional colonoscopy, Herman said.

More study of AIAC is needed, said Daniel Pambianco, MD, managing partner of GastroHealth-Charlottesville in Virginia and the 2023 ACG president. “This technology is in a fledging stage, and the more data we have, the more helpful it’ll be to know if we’re removing the right lesions at a better rate.”

“There’s a hope that assistance will improve detection, removal of polyps, and ultimately, colon cancer,” added Pambianco, who comoderated the session on colorectal cancer prevention.

Future longitudinal studies should monitor both ADR and benign lesion resection rates with AIAC, and modeling studies could determine the benefits and costs of the technology, Herman said. In addition, development of hybrid CADe and computer-aided diagnosis systems could mitigate concerns about excessive benign lesion resection with AI tools.

Valley Medical Group

Clinicians already are able to find colon mucosa that are polypoid or lymphoid aggregates during colonoscopy without AI assistance, said the session’s comoderator, Sita Chokhavatia, MD, AGAF, a gastroenterologist with Valley Medical Group in Ridgewood, New Jersey. 

“Instead, we need a tool that can help us to not remove these polyps that are not neoplastic,” she said. “With future developments, we may be able to take it to the next step where the algorithm tells us that it’s benign and not to touch it.”

The study was named an ACG Newsworthy Abstract. Herman, Pambianco, and Chokhavatia reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.