title: Androgen receptor CAG repeat length and risk of biliary tract cancer and stones.
abstract: Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are rare but highly fatal. Gallstones represent the major risk factor for biliary tract cancer, and share with gallbladder cancer a female predominance and an association with reproductive factors and obesity. Although estrogens have been implicated in earlier studies of gallbladder cancer, there are no data on the role of androgens. Because intracellular androgen activity is mediated through the androgen receptor (AR), we examined associations between AR CAG repeat length [(CAG)(n)] and the risk of biliary tract cancers and stones in a population-based study of 331 incident cancer cases, 837 gallstone cases, and 750 controls from Shanghai, China, where the incidence rates for biliary tract cancer are rising sharply. Men with (CAG)(n) >24 had a significant 2-fold risk of gallbladder cancer [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.07-3.73], relative to those with (CAG)(n) < or = 22. In contrast, women with (CAG)(n) >24 had reduced gallbladder cancer risk (OR, 0.69; 95% CI, 0.43-1.09) relative to those with (CAG)(n) < or = 22; P interaction sex = 0.01, which was most pronounced for women ages 68 to 74 (OR, 0.48; 95% CI, 0.25-0.93; P interaction age = 0.02). No associations were found for bile duct cancer or gallstones. Reasons for the heterogeneity of genetic effects by gender and age are unclear but may reflect an interplay between AR and the levels of androgen as well as estrogen in men and older women. Further studies are needed to confirm these findings and clarify the mechanisms involved.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPS Room 5032, 6120 Executive Boulevard, Rockville, MD 20852, USA. meyerte@mail.nih.gov
authors.forename: Tamra E
authors.initials: TE
authors.lastname: Meyer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: O'Brien
authors.forename: Gabriella
authors.initials: G
authors.lastname: Andreotti
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Qizhai
authors.initials: Q
authors.lastname: Li
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
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: Shelley
authors.initials: S
authors.lastname: Niwa
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
mesh_terms: D000328:Adult; D000368:Aged; D001661:Biliary Tract Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005260:Female; D042882:Gallstones / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics*; D012307:Risk Factors; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen