title: Urinary polyphenols, glutathione S-transferases copy number variation, and breast cancer risk: results from the Shanghai women's health study.
abstract: In vitro studies have found that flavanol epigallocatechin (EGC) and flavonols, but not flavanol epicatechin (EC), activate glutathione S-transferases (GSTs), a family of phase II enzymes that detoxify reactive oxygen species, such as catechol estrogen metabolites. This study was designed to investigate prospectively whether urinary excretion of tea polyphenols interacts with GST polymorphisms to influence breast cancer risk. We conducted a study of 352 incident breast cancer cases and 701 individually matched controls nested within the Shanghai Women's Health Study cohort of women aged 40-70 yr at baseline. Liquid chromatography tandem mass spectrometry was used to measure urinary excretion of flavanols and flavonols. Real-time multiplex PCR was used to quantify the copy number variation in the GSTM1 and GSTT1 genes. Urinary excretion of flavonols and flavanols, particularly EGC (P = 0.02), was significantly higher among women null for GSTM1 than those positive for GSTM1. Flavonols and flavanols (EGC in particular) were associated with a reduced risk of breast cancer among those null for GSTM1 and GSTT1, with a P-value of 0.04 for the interaction between EGC and GSTM1 polymorphism. In contrast, among women possessing both GSTM1 and GSTT1, breast cancer risk increased with levels of flavonols, particularly kaempferol. The differential associations between polyphenols and breast cancer risk by GST polymorphisms, if confirmed, may provide a new avenue for the personalized prevention of breast cancer.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203-1738, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Luo
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Xiao-ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Honglan
authors.initials: H
authors.lastname: Li
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Shrubsole
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Franke
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000652:urine; D056915:DNA Copy Number Variations; D005260:Female; D056726:Genetic Association Studies; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D059808:Polyphenols / Q000652:urine*; D012307:Risk Factors; D013662:Tea / Q000378:metabolism
chemical_list: D005982:Glutathione Transferase; D059808:Polyphenols; D013662:Tea; C413545:glutathione S-transferase T1