Abstract 3747: Leukocyte LINE1 and Alu DNA methylation and gastric cancer risk in the Shanghai Women's Health Study cohort

Aberrant DNA methylation is a well-recognized feature of malignant epithelial component in human carcinomas. Recent data also suggested a link between blood leukocyte DNA methylation and cancer risk. However, data on DNA methylation from a prospective study, which may provide evidence for causality, are unavailable. We explored the association between methylation levels in two repetitive elements, i.e. Alu and LINE-1, in blood leukocyte DNA and gastric cancer risk in a case-control study nested in the Shanghai Women9s Health Study cohort. A total of 213 incident gastric cancer cases and 426 age- and menopause status- matched controls were included in the study. Using prediagnostic DNA extracted from blood leukocytes, methylation of LINE1 and Alu were evaluated using bisulfate-pyrosequencing. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. Decreased Alu methylation was associated with increased gastric cancer risk at the lowest quartile (OR=1.85, 95%CI=1.10-3.11) compared to the highest quartile. We did not observe appreciable changes in the association with increasing interval between blood draw and cancer diagnosis or reference date for controls. Excluding the cases diagnosed within 1 year after study enrollment and their matched controls did not alter the results substantially. When stratified by potential effect modifiers, a significant interaction was observed with isoflavone intake (p=0.04), with a positive association between Alu methylation and gastric cancer risk restricted to individuals with high isoflavone intake. Associations with Alu were also strengthened among subjects with tea use and high intake of folate and fruit. Conversely, lower methylaiton levels of LINE1 were associated with slightly decreased, but not statistically significant, risk of gastric cancer. This prospective study suggests that DNA methylation of Alu in blood leukocytes may be inversely associated with risk of gastric cancer. The divergent associations with Alu and LINE1 raise the possibility that the role of DNA methylation in these two regions is different in gastric cancer etiology, and warrant further research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3747. doi:10.1158/1538-7445.AM2011-3747