title: Polymorphisms of estrogen receptors and risk of biliary tract cancers and gallstones: a population-based study in Shanghai, China.
abstract: Biliary tract cancer encompasses tumors of the gallbladder, bile duct and ampulla of Vater. Gallbladder cancer is more common in women, whereas bile duct cancer is more common in men, suggesting that sex hormones may play a role in the etiology of these cancers. The intracellular action of estrogens is regulated by the estrogen receptor (ESR); thus, we examined the role of common genetic variants in ESR genes on the risk of biliary tract cancers and stones in a population-based case-control study in Shanghai, China (411 cancer cases, 895 stone cases and 786 controls). We genotyped six single-nucleotide polymorphisms (SNPs), four in ESR1 (rs2234693, rs3841686, rs2228480 and rs1801132) and two in ESR2 (rs1256049 and rs4986938). In all participants, the ESR1 rs1801132 (P325P) G allele was associated with excess risks of bile duct [odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.1-2.8] and ampulla of Vater cancers (OR = 2.1, 95% CI 0.9-4.9) compared with the CC genotype. The association with bile duct cancer was apparent among men (OR = 2.8, 95% CI 1.4-5.7) but not among women (P-heterogeneity = 0.01). Also, the ESR2 rs4986938 (38 bp 3' of STP) GG genotype was associated with a higher risk of bile duct cancer (OR = 3.3, 95% CI 1.3-8.7) compared with the AA genotype, although this estimate was based on a small number of subjects. None of the other SNPs examined was associated with biliary tract cancers or stones. False discovery rate-adjusted P-values were not significant (P > 0.1). No association was found for ESR1 haplotype based on four SNPs. These preliminary results suggest that variants in ESR genes could play a role in the etiology of biliary tract cancers, especially bile duct cancer in men.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institute of Health, EPS-MSC 7234, 6120 Executive Boulevard, Bethesda, MD 20892-7234, USA.
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.forename: Gabriella
authors.initials: G
authors.lastname: Andreotti
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Olsen
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.forename: Mingdong
authors.initials: M
authors.lastname: Zhang
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Shen
authors.forename: Bing-Sheng
authors.initials: BS
authors.lastname: Wang
authors.forename: Tian-Quan
authors.initials: TQ
authors.lastname: Han
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Zhang
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
mesh_terms: D000368:Aged; D001661:Biliary Tract Neoplasms / Q000209:etiology / Q000235:genetics*; D015992:Body Mass Index; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D042882:Gallstones / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta