Aspects of the etiology of gastric adenocarcinoma

Abstract: Gastric adenocarcinoma is the fourth most common malignancy and the second leading cause of cancer death in the world. Tremendous effort has been made to look into the causation of gastric cancer. Etiological research plays a key role in identifying possible preventive and interventional measures. This thesis is based on four large prospective, population-based cohort studies, focusing on environmental risk factors for gastric cancer other than infection with Helicobacter pylori. In the first study, the relations of tobacco smoking and alcohol to gastric cancer were investigated in a public health survey of the adult population of the Nord-Trondelag County in Norway (HUNT-1). During follow-up, we identified 251 new cases of gastric cancer. The risk of noncardia gastric cancer was almost twice as high in daily smokers as in non-smokers. Earlier age at initiation of daily smoking was associated with an increased risk of non-cardia gastric cancer, independently of adjustment for duration of smoking, suggesting a dose-response relation with earlier onset of smoking. Excessive smoking combined with high alcohol intake was associated with a nearly 5-fold increase in risk of non-cardia gastric cancer, compared to non-users. In the second study, we hypothesized that specific airborne exposures, which often occur in the male-dominated construction industry, such as dust, fumes, and solvents, could be inhaled and swallowed and have a direct harmful effect on the gastric mucosa. To elucidate the relation between such exposures and risk of gastric cancer in a male-dominated industry, we used prospectively collected data from the Swedish Construction Workers Cohort. In total, 948 incident cases of gastric cancer were identified. There were seemingly dose-response positive associations between exposure to cement dust, quartz dust, and diesel exhaust and risk of gastric cancer. Increased risk of this tumor was found among workers exposed to cement dust (IRR 1.5 [95% CI 1.1-2.1]), quartz dust (IRR 1.3 [95% CI 1.0-1.7]), and diesel exhaust (IRR 1.4 [95% CI 1.1-1.9]). In the third study, we prospectively investigated the influence of body mass index (BMI) and recreational physical activity on risk of gastric cancer in the HUNT-1 cohort. No statistically significant association was found between different levels of BMI and risk of gastric cancer. A statistically significant 40-50% decrease in the risk of gastric cancer was seen among persons who had at least a moderate level of recreational physical activity, and a dose-response relation was indicated. In the fourth study, we assessed the effect of dietary salt intake on the risk of gastric cancer in a low-incidence Western region, again based on the HUNT-1 cohort. There was no statistically significant association between level of intake of salted foods and risk of gastric adenocarcinoma. This result highlights the question as to whether cofactors more prevalent in high-incidence populations, such as other dietary factors and Helicobacter pylori infection, interact with salt in producing a potentially carcinogenic effect on the gastric mucosa, or whether previously reported positive associations might have been an artifact of residual confounding by such factors.