User login
Genetic Colorectal Cancer Risk Variants are Associated with Increasing Adenoma Counts
Background: High lifetime counts of pre-cancerous polyps, termed “adenomas,” are associated with increased risk for colorectal cancer (CRC). Given that a genetic predisposition to adenomas may increase susceptibility to CRC, further studies are needed to characterize low-penetrance germline factors in those with increased cumulative adenoma counts.
Purpose: To investigate if known CRC or adenomarisk single nucleotide polymorphisms (SNPs) are associated with increasing cumulative adenoma counts in a prospective screening cohort of veterans.
Data Analysis: The CSP #380 screening colonoscopy cohort includes a biorepository of selected individuals with baseline advanced neoplasia and matched individuals without neoplasia (n=612). Blood samples were genotyped using the Illumina Infinium Omni2.5-8 GWAS chip and associated cumulative adenoma counts were summed over 10 years. A corrected Poisson regression (adjusted for age at last colonoscopy, gender, and race) was used to evaluate associations between higher cumulative adenoma counts and 43 pre-specified CRC-risk SNPs or a subset of these SNPs shown also to be associated with adenomas in published literature. SNPs were evaluated singly or combined in a Genetic Risk Score (GRS). The GRS was constructed from only the eight adenomarisk SNPs and calculated based on the total number of present risk alleles (0-2) summed across all SNPs per individual (both weighted for published effect size and unweighted).
Results: Four CRC-risk SNPs were associated with increasing mean adenoma counts (P<0.05): rs12241008 (gene: VTI1A), rs2423279 (BMP2/HAO1), rs3184504 (SH2B3), and rs961253 (FERMT1/BMP2), with risk allele risk ratios (RR) of 1.31, 1.29, 1.24, and 1.23, respectively. Only one known adenoma-risk SNP was significant in our dataset (rs961253; OR 1.23 per risk allele; P=0.01). An increasing weighted GRS was associated with increased cumulative adenoma counts (weighted RR 1.58, P=0.03; unweighted RR 1.03, P=0.39).
Implications: In this CRC screening cohort, four known CRC-risk SNPs were found to be associated with increasing cumulative adenoma counts. Additionally, an increasing burden of adenoma-risk SNPs, as measured by a weighted GRS, was associated with higher cumulative adenoma counts. Future work will evaluate predictive tools based on a precancerous, adenoma GRS to better risk stratify patients during CRC screening, and compare to current CRC genetic risk scores.
Background: High lifetime counts of pre-cancerous polyps, termed “adenomas,” are associated with increased risk for colorectal cancer (CRC). Given that a genetic predisposition to adenomas may increase susceptibility to CRC, further studies are needed to characterize low-penetrance germline factors in those with increased cumulative adenoma counts.
Purpose: To investigate if known CRC or adenomarisk single nucleotide polymorphisms (SNPs) are associated with increasing cumulative adenoma counts in a prospective screening cohort of veterans.
Data Analysis: The CSP #380 screening colonoscopy cohort includes a biorepository of selected individuals with baseline advanced neoplasia and matched individuals without neoplasia (n=612). Blood samples were genotyped using the Illumina Infinium Omni2.5-8 GWAS chip and associated cumulative adenoma counts were summed over 10 years. A corrected Poisson regression (adjusted for age at last colonoscopy, gender, and race) was used to evaluate associations between higher cumulative adenoma counts and 43 pre-specified CRC-risk SNPs or a subset of these SNPs shown also to be associated with adenomas in published literature. SNPs were evaluated singly or combined in a Genetic Risk Score (GRS). The GRS was constructed from only the eight adenomarisk SNPs and calculated based on the total number of present risk alleles (0-2) summed across all SNPs per individual (both weighted for published effect size and unweighted).
Results: Four CRC-risk SNPs were associated with increasing mean adenoma counts (P<0.05): rs12241008 (gene: VTI1A), rs2423279 (BMP2/HAO1), rs3184504 (SH2B3), and rs961253 (FERMT1/BMP2), with risk allele risk ratios (RR) of 1.31, 1.29, 1.24, and 1.23, respectively. Only one known adenoma-risk SNP was significant in our dataset (rs961253; OR 1.23 per risk allele; P=0.01). An increasing weighted GRS was associated with increased cumulative adenoma counts (weighted RR 1.58, P=0.03; unweighted RR 1.03, P=0.39).
Implications: In this CRC screening cohort, four known CRC-risk SNPs were found to be associated with increasing cumulative adenoma counts. Additionally, an increasing burden of adenoma-risk SNPs, as measured by a weighted GRS, was associated with higher cumulative adenoma counts. Future work will evaluate predictive tools based on a precancerous, adenoma GRS to better risk stratify patients during CRC screening, and compare to current CRC genetic risk scores.
Background: High lifetime counts of pre-cancerous polyps, termed “adenomas,” are associated with increased risk for colorectal cancer (CRC). Given that a genetic predisposition to adenomas may increase susceptibility to CRC, further studies are needed to characterize low-penetrance germline factors in those with increased cumulative adenoma counts.
Purpose: To investigate if known CRC or adenomarisk single nucleotide polymorphisms (SNPs) are associated with increasing cumulative adenoma counts in a prospective screening cohort of veterans.
Data Analysis: The CSP #380 screening colonoscopy cohort includes a biorepository of selected individuals with baseline advanced neoplasia and matched individuals without neoplasia (n=612). Blood samples were genotyped using the Illumina Infinium Omni2.5-8 GWAS chip and associated cumulative adenoma counts were summed over 10 years. A corrected Poisson regression (adjusted for age at last colonoscopy, gender, and race) was used to evaluate associations between higher cumulative adenoma counts and 43 pre-specified CRC-risk SNPs or a subset of these SNPs shown also to be associated with adenomas in published literature. SNPs were evaluated singly or combined in a Genetic Risk Score (GRS). The GRS was constructed from only the eight adenomarisk SNPs and calculated based on the total number of present risk alleles (0-2) summed across all SNPs per individual (both weighted for published effect size and unweighted).
Results: Four CRC-risk SNPs were associated with increasing mean adenoma counts (P<0.05): rs12241008 (gene: VTI1A), rs2423279 (BMP2/HAO1), rs3184504 (SH2B3), and rs961253 (FERMT1/BMP2), with risk allele risk ratios (RR) of 1.31, 1.29, 1.24, and 1.23, respectively. Only one known adenoma-risk SNP was significant in our dataset (rs961253; OR 1.23 per risk allele; P=0.01). An increasing weighted GRS was associated with increased cumulative adenoma counts (weighted RR 1.58, P=0.03; unweighted RR 1.03, P=0.39).
Implications: In this CRC screening cohort, four known CRC-risk SNPs were found to be associated with increasing cumulative adenoma counts. Additionally, an increasing burden of adenoma-risk SNPs, as measured by a weighted GRS, was associated with higher cumulative adenoma counts. Future work will evaluate predictive tools based on a precancerous, adenoma GRS to better risk stratify patients during CRC screening, and compare to current CRC genetic risk scores.
Clinical Risk Group at Baseline Is Associated With 10 Year Outcomes in a Screening Cohort: A Longitudinal Analysis of the CSP 380 Cohort
Background: CSP 380-Risk Factors for Large Colonic Adenomas, a screening colonoscopy study, enrolled 3,121 patients from 1994-97 at 13 VA sites. We report 10 year outcomes based on risk group after baseline colonoscopy.
Methods: Asymptomatic veterans age 50-75 who had not undergone colorectal cancer (CRC) screening in the prior 10 years underwent colonoscopy and were classified into 6 risk groups: no neoplasia, 1-2 small adenomas, 3-10 adenomas, > 10 adenomas, advanced adenoma (polyp ≥ 1 cm, villous histology, or high grade dysplasia), and CRC. Subjects were followed for 10 years until death or last colonoscopy. We report the proportions who developed advanced neoplasia (AN, defined as advanced adenoma or CRC) and CRC.
Results: Of the patients enrolled, 1,917 had at least one follow-up colonoscopy. Of these 1,917, 933 had no neoplasia at baseline; 4.0% developed AN, including 0.8% with CRC. At baseline, 560 patients had 1-2 small adenomas; 5.9% developed AN, including 0.9% with CRC. For those with 3-10 adenomas (134), 15.7% developed AN, including 0.7% with CRC. Two had > 10 adenomas; neither developed AN or CRC. At baseline, 265 patients had advanced adenoma; 19.2% developed AN, including 1.9% with CRC. Twenty-three patients had baseline CRC; 34.8% developed AN, including 21.7% with CRC. Patients with baseline CRC were at highest risk of developing AN. Those with advanced adenoma or 3-10 adenomas were at moderate risk. Those with no neoplasia or 1-2 small adenomas were at lowest risk. Except for those with baseline CRC, all risk groups showed a dramatic decline in CRC incidence after 3 years, with 10-year CRC risk similar to those with no neoplasia at baseline.
Conclusion: 1) Baseline colonoscopy result is a predictor of future risk for AN. 2) Those with baseline CRC remain at risk for recurrence. Intensive surveillance is warranted. 3) Those with 1-2 small adenomas or no adenomas at baseline have a low risk of AN after 2-3 years, and may not need surveillance. 4) Those with baseline advanced adenoma or > 3 adenomas show a dramatic decline in CRC risk after 3 years, suggesting that frequent surveillance may only be necessary in the first 5 years.
Background: CSP 380-Risk Factors for Large Colonic Adenomas, a screening colonoscopy study, enrolled 3,121 patients from 1994-97 at 13 VA sites. We report 10 year outcomes based on risk group after baseline colonoscopy.
Methods: Asymptomatic veterans age 50-75 who had not undergone colorectal cancer (CRC) screening in the prior 10 years underwent colonoscopy and were classified into 6 risk groups: no neoplasia, 1-2 small adenomas, 3-10 adenomas, > 10 adenomas, advanced adenoma (polyp ≥ 1 cm, villous histology, or high grade dysplasia), and CRC. Subjects were followed for 10 years until death or last colonoscopy. We report the proportions who developed advanced neoplasia (AN, defined as advanced adenoma or CRC) and CRC.
Results: Of the patients enrolled, 1,917 had at least one follow-up colonoscopy. Of these 1,917, 933 had no neoplasia at baseline; 4.0% developed AN, including 0.8% with CRC. At baseline, 560 patients had 1-2 small adenomas; 5.9% developed AN, including 0.9% with CRC. For those with 3-10 adenomas (134), 15.7% developed AN, including 0.7% with CRC. Two had > 10 adenomas; neither developed AN or CRC. At baseline, 265 patients had advanced adenoma; 19.2% developed AN, including 1.9% with CRC. Twenty-three patients had baseline CRC; 34.8% developed AN, including 21.7% with CRC. Patients with baseline CRC were at highest risk of developing AN. Those with advanced adenoma or 3-10 adenomas were at moderate risk. Those with no neoplasia or 1-2 small adenomas were at lowest risk. Except for those with baseline CRC, all risk groups showed a dramatic decline in CRC incidence after 3 years, with 10-year CRC risk similar to those with no neoplasia at baseline.
Conclusion: 1) Baseline colonoscopy result is a predictor of future risk for AN. 2) Those with baseline CRC remain at risk for recurrence. Intensive surveillance is warranted. 3) Those with 1-2 small adenomas or no adenomas at baseline have a low risk of AN after 2-3 years, and may not need surveillance. 4) Those with baseline advanced adenoma or > 3 adenomas show a dramatic decline in CRC risk after 3 years, suggesting that frequent surveillance may only be necessary in the first 5 years.
Background: CSP 380-Risk Factors for Large Colonic Adenomas, a screening colonoscopy study, enrolled 3,121 patients from 1994-97 at 13 VA sites. We report 10 year outcomes based on risk group after baseline colonoscopy.
Methods: Asymptomatic veterans age 50-75 who had not undergone colorectal cancer (CRC) screening in the prior 10 years underwent colonoscopy and were classified into 6 risk groups: no neoplasia, 1-2 small adenomas, 3-10 adenomas, > 10 adenomas, advanced adenoma (polyp ≥ 1 cm, villous histology, or high grade dysplasia), and CRC. Subjects were followed for 10 years until death or last colonoscopy. We report the proportions who developed advanced neoplasia (AN, defined as advanced adenoma or CRC) and CRC.
Results: Of the patients enrolled, 1,917 had at least one follow-up colonoscopy. Of these 1,917, 933 had no neoplasia at baseline; 4.0% developed AN, including 0.8% with CRC. At baseline, 560 patients had 1-2 small adenomas; 5.9% developed AN, including 0.9% with CRC. For those with 3-10 adenomas (134), 15.7% developed AN, including 0.7% with CRC. Two had > 10 adenomas; neither developed AN or CRC. At baseline, 265 patients had advanced adenoma; 19.2% developed AN, including 1.9% with CRC. Twenty-three patients had baseline CRC; 34.8% developed AN, including 21.7% with CRC. Patients with baseline CRC were at highest risk of developing AN. Those with advanced adenoma or 3-10 adenomas were at moderate risk. Those with no neoplasia or 1-2 small adenomas were at lowest risk. Except for those with baseline CRC, all risk groups showed a dramatic decline in CRC incidence after 3 years, with 10-year CRC risk similar to those with no neoplasia at baseline.
Conclusion: 1) Baseline colonoscopy result is a predictor of future risk for AN. 2) Those with baseline CRC remain at risk for recurrence. Intensive surveillance is warranted. 3) Those with 1-2 small adenomas or no adenomas at baseline have a low risk of AN after 2-3 years, and may not need surveillance. 4) Those with baseline advanced adenoma or > 3 adenomas show a dramatic decline in CRC risk after 3 years, suggesting that frequent surveillance may only be necessary in the first 5 years.
Risk Factors Associated With the Development of Adenoma Multiplicity in a Screening Cohort
Background: Colorectal cancer (CRC) screening guidelines in the U.S. recommend genetic evaluation for individuals with ≥ 10 cumulative colorectal adenomas, as they are thought to have an increased risk for underlying hereditary CRC syndromes. However, little is known about the prevalence, clinical characteristics, and long-term outcomes of patients with ≥ 10 cumulative adenomas.
Aims: To estimate the proportion of patients in a screening cohort who are found to have ≥ 10 cumulative adenomas, examine the demographic and baseline clinical risk factors associated with having ≥ 10 cumulative adenomas, and describe the prevalence of advanced neoplasia (AN) and CRC in these patients.
Patients and Methods: The CSP 380 cohort comprises 3,121 asymptomatic veterans aged 50-75 from 13 VA sites who underwent a screening colonoscopy from 1994-97 and were followed for 10 years until death or last colonoscopy. Of these 3,121 patients, 3,089 did not have CRC at baseline. We identified patients with ≥ 10 cumulative adenomas and compared baseline factors (gender, race, family history of CRC, age, BMI, tobacco use, and alcohol use) in patients with and without ≥ 10 cumulative adenomas. We then estimated the age to ≥ 10 cumulative adenomas. Finally, we calculated the prevalence of AN (polyp ≥ 1 cm, villous histology, high grade dysplasia, or CRC) in patients with ≥ 10 adenomas and those with 0-9 adenomas.
Results: Ten or more cumulative adenomas were found in 66 (2.1%) of the 3089 patients in a 10-year period. Age 60-69 is the single baseline risk factor associated with this outcome. Of the 3,023 patients with 0-9 cumulative adenomas, 348 (11.5%) developed AN, including 23 (0.8%) with CRC. Of the 66 patients with ≥ 10 adenomas, 42 (63.6%) developed AN, including 2 (3.0%) with CRC.
Conclusion: The prevalence of ≥ 10 cumulative adenomas was 2% in this screening population, with few cases before age 60. Few patients with this outcome, however, develop CRC within a 10-year period. Future work could identify additional risk factors associated with the development of ≥ 10 cumulative adenomas in order to create a risk stratification tool that may lead to the earlier detection of patients at high risk for hereditary CRC syndromes, AN, and CRC.
Background: Colorectal cancer (CRC) screening guidelines in the U.S. recommend genetic evaluation for individuals with ≥ 10 cumulative colorectal adenomas, as they are thought to have an increased risk for underlying hereditary CRC syndromes. However, little is known about the prevalence, clinical characteristics, and long-term outcomes of patients with ≥ 10 cumulative adenomas.
Aims: To estimate the proportion of patients in a screening cohort who are found to have ≥ 10 cumulative adenomas, examine the demographic and baseline clinical risk factors associated with having ≥ 10 cumulative adenomas, and describe the prevalence of advanced neoplasia (AN) and CRC in these patients.
Patients and Methods: The CSP 380 cohort comprises 3,121 asymptomatic veterans aged 50-75 from 13 VA sites who underwent a screening colonoscopy from 1994-97 and were followed for 10 years until death or last colonoscopy. Of these 3,121 patients, 3,089 did not have CRC at baseline. We identified patients with ≥ 10 cumulative adenomas and compared baseline factors (gender, race, family history of CRC, age, BMI, tobacco use, and alcohol use) in patients with and without ≥ 10 cumulative adenomas. We then estimated the age to ≥ 10 cumulative adenomas. Finally, we calculated the prevalence of AN (polyp ≥ 1 cm, villous histology, high grade dysplasia, or CRC) in patients with ≥ 10 adenomas and those with 0-9 adenomas.
Results: Ten or more cumulative adenomas were found in 66 (2.1%) of the 3089 patients in a 10-year period. Age 60-69 is the single baseline risk factor associated with this outcome. Of the 3,023 patients with 0-9 cumulative adenomas, 348 (11.5%) developed AN, including 23 (0.8%) with CRC. Of the 66 patients with ≥ 10 adenomas, 42 (63.6%) developed AN, including 2 (3.0%) with CRC.
Conclusion: The prevalence of ≥ 10 cumulative adenomas was 2% in this screening population, with few cases before age 60. Few patients with this outcome, however, develop CRC within a 10-year period. Future work could identify additional risk factors associated with the development of ≥ 10 cumulative adenomas in order to create a risk stratification tool that may lead to the earlier detection of patients at high risk for hereditary CRC syndromes, AN, and CRC.
Background: Colorectal cancer (CRC) screening guidelines in the U.S. recommend genetic evaluation for individuals with ≥ 10 cumulative colorectal adenomas, as they are thought to have an increased risk for underlying hereditary CRC syndromes. However, little is known about the prevalence, clinical characteristics, and long-term outcomes of patients with ≥ 10 cumulative adenomas.
Aims: To estimate the proportion of patients in a screening cohort who are found to have ≥ 10 cumulative adenomas, examine the demographic and baseline clinical risk factors associated with having ≥ 10 cumulative adenomas, and describe the prevalence of advanced neoplasia (AN) and CRC in these patients.
Patients and Methods: The CSP 380 cohort comprises 3,121 asymptomatic veterans aged 50-75 from 13 VA sites who underwent a screening colonoscopy from 1994-97 and were followed for 10 years until death or last colonoscopy. Of these 3,121 patients, 3,089 did not have CRC at baseline. We identified patients with ≥ 10 cumulative adenomas and compared baseline factors (gender, race, family history of CRC, age, BMI, tobacco use, and alcohol use) in patients with and without ≥ 10 cumulative adenomas. We then estimated the age to ≥ 10 cumulative adenomas. Finally, we calculated the prevalence of AN (polyp ≥ 1 cm, villous histology, high grade dysplasia, or CRC) in patients with ≥ 10 adenomas and those with 0-9 adenomas.
Results: Ten or more cumulative adenomas were found in 66 (2.1%) of the 3089 patients in a 10-year period. Age 60-69 is the single baseline risk factor associated with this outcome. Of the 3,023 patients with 0-9 cumulative adenomas, 348 (11.5%) developed AN, including 23 (0.8%) with CRC. Of the 66 patients with ≥ 10 adenomas, 42 (63.6%) developed AN, including 2 (3.0%) with CRC.
Conclusion: The prevalence of ≥ 10 cumulative adenomas was 2% in this screening population, with few cases before age 60. Few patients with this outcome, however, develop CRC within a 10-year period. Future work could identify additional risk factors associated with the development of ≥ 10 cumulative adenomas in order to create a risk stratification tool that may lead to the earlier detection of patients at high risk for hereditary CRC syndromes, AN, and CRC.