Abstract 4919: Body mass index interacts with DNA global methylation levels to predict bladder cancer in The Shanghai Bladder Cancer Study

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Bladder cancer is a relatively common and costly disease, and although most frequently associated with tobacco smoking, there are several environmental and occupational exposure contaminants associated with bladder cancer which are mostly found in urban settings. As nations become more developed they may become more susceptible to bladder cancer as a result of urbanization, as well as changes in dietary and lifestyle risk factors associated with developed countries. Recent research suggests that in addition to mutagenic effects, environmental exposures may be linked to epigenetic alterations, including changes in global DNA methylation, which have previously been associated with risk of bladder cancer. Therefore, we have sought to examine the association between environmental exposures and global DNA methylation, and risk of bladder cancer in in Shanghai, China. Methods: The Shanghai Bladder Cancer Study is a population-based case-control study in Shanghai with 581 bladder cancer patients, 25-74yrs of age at diagnosis between 1995-1998, and 604 healthy community control subjects comparable by gender and age. In addition to an in-person interview to gather information on body weight, height, smoking history, and other lifestyle factors, blood and urine samples were collected from all subjects. We utilized quantitative bisulfite pyrosequencing of the LINE-1 repetitive elements of DNA extracted from peripheral blood samples as a surrogate measure for genome-wide methylation. Odds ratios and 95% confidence intervals for bladder cancer associated with LINE-1 values were calculated using unconditional logistic regression methods for all study subjects as well as for subgroups stratified by body mass index (BMI) and smoking status. Results: Among individuals with BMI >25 kg/m2, 28% of bladder cancer cases versus 15% controls possessed the highest quintile of LINE-1 values (>83.38) (P = 0.098). This difference in global DNA methylation between cases and controls became more apparent among current smokers (P=0.03), and in long-term (>20 years) smokers (P=0.009). Conclusion: We found that BMI and smoking are significant risk factors for bladder cancer, and have the ability to predict case status in our study. Using logistic regression analysis, we also found a significant interaction between BMI and global DNA methylation that is a significant predictor of case status. This association between BMI and global DNA methylation is especially prominent among smokers. BMI is a known risk factor for various cancers, although the mechanisms underlying this association are not well understood. These data suggest that smoking and BMI might influence bladder cancer etiology through epigenetic mechanisms. Due to rapidly rising rates of global obesity, it is important that we understand the impact of BMI on DNA methylation, and how it relates to cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4919.