Assessment and management of modifiable risk factors
Helicobacter pylori, a group 1 carcinogen, is the most well-recognized risk factor for gastric cancer, particularly noncardia gastric cancer.11 Since a landmark longitudinal follow-up study in Japan demonstrated that people with H. pylori infection are more likely to develop gastric cancer than those without H. pylori infection,12 accumulating evidence largely from Asian countries has shown that eradication of H. pylori is associated with a reduced incidence of gastric cancer regardless of baseline risk.13 There are also data on the protective effect for gastric cancer of H. pylori eradication in asymptomatic individuals. Another meta-analysis of six international randomized control trials demonstrated a 34% relative risk reduction of gastric cancer occurrence in asymptomatic people (relative risk of developing gastric cancer was 0.66 in those who received eradication therapy compared with those with placebo or no treatment, 95% CI, 0.46-0.95).14 A U.S. practice guideline published after these meta-analyses recommends that all patients with a positive test indicating active infection with H. pylori should be offered treatment and testing to prove eradication,15 though the recommendation was not purely intended to reduce the gastric cancer risk in U.S. population. Subsequently, a Department of Veterans Affairs cohort study added valuable insights from a U.S. experience to the body of evidence from other countries with higher prevalence. In this study of more than 370,000 patients with a history of H. pylori infection, the detection and successful eradication of H. pylori was associated with a 76% lower incidence of gastric cancer compared with people without H. pylori treatment.16 This study also provided insight into H. pylori treatment practice patterns. Of patients with a positive H. pylori test result (stool antigen, urea breath test, or pathology), approximately 75% were prescribed an eradication regimen and only 21% of those underwent eradication tests. A low rate (24%) of eradication testing was subsequently reported by the same group among U.S. patients regardless of gastric cancer risk profiles.17 The lesson from the aforementioned study is that treatment and eradication of H. pylori even among asymptomatic U.S. patients reduces the risk of subsequent gastric cancer. However, it may be difficult to generalize the results of this study given the nature of the Veterans Affairs cohort, and more data are required to justify the implementation of nationwide preventive H. pylori screening in the general U.S. population.
Smoking has been recognized as the other important risk factor. A study from the European prospective multicenter cohort demonstrated a significant association of cigarette smoking and gastric cancer risk (HR for ever-smokers 1.45 [95% CI, 1.08-1.94], current-smokers in males 1.73 [95% CI, 1.06-2.83], and current smokers in females 1.87 [95% CI, 1.12-3.12], respectively) after adjustment for educational level, dietary consumption profiles, alcohol intake, and body mass index (BMI).18 A subsequent meta-analysis provided solid evidence of smoking as the important behavioral risk factor for gastric cancer.19 Smoking also predisposed to the development of proximal gastric cancer.20 Along with other cancers in the digestive system such as in the esophagus, colon and rectum, liver, gallbladder, and pancreas, a significant association of BMI and the risk of proximal gastric cancer (RR of the highest BMI category compared with normal BMI, 1.8 [95% CI, 1.3-2.5]) was reported, with positive dose-response relationships; however, the association was not sufficient for distal gastric cancer.21 There is also evidence to show a trend of greater alcohol consumption (>45 grams per day [about 3 drinks a day]) associated with the increased risk of gastric cancer.21 It has been thought that salt and salt-preserved food increase the risk of gastric cancer. It should be noted that the observational studies showing the associations were published from Asian countries where such foods were a substantial part of traditional diets (e.g., salted vegetables in Japan) and the incidence of gastric cancer is high. There is also a speculation that preserved foods may have been eaten in more underserved, low socioeconomic regions where refrigeration was not available and prevalence of H. pylori infection was higher. Except for documented inherited form of gastric cancer (e.g., HDGC or hereditary cancer syndromes), most gastric cancers are considered sporadic. A recent randomized study published from South Korea investigated a cohort of higher-risk asymptomatic patients with family history significant for gastric cancer. This study of 1,676 subjects with a median follow-up of 9.2 years showed that successful eradication of H. pylori in the first-degree relatives of those with gastric cancer significantly reduced the risk (HR 0.45 [95% CI, 0.21-0.94]) of developing gastric cancer.22 As previously discussed, in the United States where the prevalence of H. pylori and the incidence of gastric cancer are both lower than in some Asian countries, routine screening of asymptomatic individuals for H. pylori is not justified yet. There may be a role for screening individuals who are first-generation immigrants from areas of high gastric cancer incidence and also have a first-degree relative with gastric cancer.