LINE-1 hypomethylation is associated with bladder cancer risk among nonsmoking Chinese

Reduced levels of global DNA methylation, assessed in peripheral blood, have been associated with bladder cancer risk in European and American populations. Similar data are lacking in Asian populations where genetic differences, lifestyle factors and different environmental exposures may affect DNA methylation and its risk relationship with bladder cancer. The association between global DNA methylation measured at long interspersed nuclear element (LINE-1) repeat regions through bisulfite pyrosequencing in lymphocyte DNA and bladder cancer risk was examined in a case-control study of 510 bladder cancer patients and 528 healthy control subjects in Shanghai, China. In an initial analysis restricted to control subjects, LINE-1 methylation was elevated among men, those who frequently consumed cruciferous vegetables and those with a null genotype for either glutathione S-transferase M1 (GSTM1) or GSTT1. In contrast, reduced LINE-1 methylation was found in current smokers with a high-cytochrome P450 1A2 (CYP1A2) phenotype index. In a case-control analysis, there was no significant association of LINE-1 methylation with case status, although reduced LINE-1 methylation was associated with increased risk of bladder cancer among never smokers (p for trend = 0.03); analysis by tertile revealed odds ratios (ORs) of 1.91 (lowest tertile; 95% CI = 1.17-3.13) and 1.34 (middle tertile; 95% CI = 0.79-2.28) when compared with the highest tertile. This association was strongest among nonsmokers null for either the GSTM1 or GSTT1 genotype (p for trend = 0.006). Further research is needed to understand the relationships between methyl group availability and LINE-1 methylation in relation to bladder cancer risk.