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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.

SUBMITTER: Meyer TE 

PROVIDER: S-EPMC2837546 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Androgen receptor CAG repeat length and risk of biliary tract cancer and stones.

Meyer Tamra E TE   O'Brien Thomas G TG   Andreotti Gabriella G   Yu Kai K   Li Qizhai Q   Gao Yu-Tang YT   Rashid Asif A   Shen Ming-Chang MC   Wang Bing-Sheng BS   Han Tian-Quan TQ   Zhang Bai-He BH   Niwa Shelley S   Fraumeni Joseph F JF   Hsing Ann W AW  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20100303 3


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 t  ...[more]

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