Combined effects of MDM2 SNP309 and TP53 R72P polymorphisms, and soy isoflavones on breast cancer risk among Chinese women in Singapore.

摘要: The MDM2 oncoprotein regulates the p53 pathway and, while functional polymorphisms of and genes have been investigated for association with breast cancer risk, results are largely null or non-conclusive. We earlier reported that increased intake soy isoflavones reduces risk postmenopausal cancer, experimental studies suggest dietary can down-regulate expression oncoprotein. In this study, we between SNP309 TP53 R72P using a case–control study 403 cases 662 controls nested among 35,303 women in Singapore Chinese Health Study, population-based, prospective cohort middle-aged elderly men who continuously followed since 1993. G allele polymorphism T were putative high-risk alleles exhibited combined gene–dose-dependent joint effect on was more clearly observed women. Among women, simultaneous presence associated an odds ratio (OR) 2.42 [95% confidence interval (CI) 1.06–5.50]. Furthermore, protective mainly confined to homozygous high activity (GG genotype). genetic subgroup, consuming levels above median level half those below (OR 0.52; 95% CI 0.28–0.99). Our findings support data implicating effects protein p53-mediated carcinogenesis, may exert via down-regulation protein.