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Cigarette smoking, Alcohol and Obesity

Cigarette Smoking

Tobacco has long been established as a carcinogen, and numerous epidemiologic studies have demonstrated an association between cigarette smoking and gastric cancer.83 Several large cohort studies from Europe and Asia have reported a significantly increased risk of gastric cancer among smokers.84-86 A recent meta-analysis found that, compared to never smokers, current smokers had a 1.5- to 2-fold increased risk of gastric cancer, both for the cardia and non-cardia region.87 The authors also reported an increased association with greater amounts of smoking.

Moist snuff is a smokeless tobacco product promoted as an alternative to cigarettes that has reportedly reduced levels of carcinogenic nitrosamines. Nevertheless, results of a Swedish cohort study demonstrated a 1.4-fold increased risk of noncardia gastric cancer among regular snuff users.88 Snuff exposure also increases the rate of gastric carcinogenesis in Hp-infected mice.89

Alcohol

Most epidemiologic studies have failed to demonstrate an association between alcohol consumption and cardia or noncardia gastric cancer.86,90,91 A separate population-based casecontrol study in the USA also found no association between any alcohol use and risk of cardia or noncardia gastric cancer, although there was a reduced risk seen with wine consumption.92 However, a meta-analysis suggested a small but significant association between heavy alcohol use and gastric cancer risk (RR, 1.20), an association largely isolated to non-cardia tumors.93 Interestingly, alcohol intake may increase the risk of gastric cancer in patients with certain polymorphisms of the alcohol dehydrogenase gene.94

Obesity

Obesity is a recognized risk factor for numerous GI malignancies.95 Increased BMI is associated with a mild to moderate increased risk of gastric cardia cancer, but not non-cardia cancer.96-99 Results of the National Institutes of Health– American Association of Retired Persons (NIH-AARP) Diet and Health Cohort Study demonstrated that morbid obesity (defined as a BMI ≥ 35) as well as large waist circumference were associated with a 2- to 3-fold increased risk of gastric cardia cancer, but not non-cardia cancer.100 A separate cohort study from the Netherlands also found an increased risk of cardia cancer with increasing BMI.96 The association between obesity and cardia cancer risk is likely mediated by proinflammatory cytokines and adipokines produced by intra-abdominal visceral fat.101