Abstract
Abstract Background: Studies of the familial associations of gastric cancer risk have largely been limited to case-control approaches which are susceptible to recall bias and cannot distinguish temporality. Furthermore, associations with family history could be explained by shared exposure to Helicobacter pylori infection, the most important environmental risk factor for gastric cancer. Notably, the risks of early onset disease and diffuse-type tumors are thought to have a greater genetic component. We therefore examined in a prospective study the associations of gastric cancer risk with history of gastric cancer in first degree relatives, controlling for H. pylori infection. Methods: We selected 405 incident gastric cancer cases and 4,129 controls with known H. pylori serology status from the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study among male smokers aged 50-69 at baseline. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression with adjustment for H. pylori and other potential confounders. All statistical tests were two-sided. Results: Family history of gastric cancer was associated with increased risk (OR=1.84, 95% CI=1.32-2.58). The association appeared stronger with gastric cancer in siblings (OR=2.87, 95% CI=1.64-5.03) than with gastric cancer in parents (OR=1.53, 95% CI=1.05-2.24). Distinguishing cases by anatomic subsite, the family history association was significant for noncardia gastric cancer (n=305; OR=2.15, 95% CI=1.50-3.07), but not for cardia cancer (n=100; OR=1.25, 95% CI=0.63-2.49). With regard to histological subtype, family history was significantly associated with both diffuse-type (n=90; OR=2.12, 95% CI=1.10-4.12) and intestinal-type (n=153; OR=1.70, 95% CI=1.02-2.83) gastric cancer. In age-specific analyses, the association with family history was strongest in the youngest age-group at baseline 50-54 years (OR=3.42, 95% CI=1.85-6.30) and absent in the oldest age group 65-69 years (OR=0.85, 95% CI=0.28-2.58). Conclusion: The results suggest that certain subtypes of sporadic gastric cancer are strongly associated with family history of gastric cancer. These associations do not appear to be explained by the associations with H. pylori infection. Citation Format: Minkyo Song, Maria Constanza Camargo, Stephanie J. Weinstein, Demetrius Albanes, Charles S. Rabkin. Family history in first degree relatives and risk of gastric cancer in the alpha-tocopherol, beta-carotene cancer prevention study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4270. doi:10.1158/1538-7445.AM2017-4270
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