Abstract
Background: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer.Methods: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case-control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n=192) and matched controls (n=384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. Results: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43-4.13), 1.47(0.85-2.57), and 2.22 (1.28-3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. Conclusion: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.
Original language | English (US) |
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Pages (from-to) | 585-591 |
Number of pages | 7 |
Journal | British Journal of Cancer |
Volume | 106 |
Issue number | 3 |
DOIs | |
State | Published - Jan 31 2012 |
Funding
This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. Dr Baccarelli is partially supported by New Investigator funding from NIEHS (ES00002). Finally, we acknowledge the study participants for donating their time and making this study possible.
Keywords
- DNA methylation
- Gastric cancer
- Leukocyte
ASJC Scopus subject areas
- Oncology
- Cancer Research