CYP17 MspA1 polymorphism and risk of biliary tract cancers and gallstones: A population-based study in Shanghai, China
Version of Record online: 27 DEC 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 118, Issue 11, pages 2847–2853, 1 June 2006
How to Cite
Hou, L., Xu, J., Gao, Y.-T., Rashid, A., Zheng, S. L., Sakoda, L. C., Shen, M.-C., Wang, B.-S., Deng, J., Han, T.-Q., Zhang, B.-H., Meyers, D. A., Fraumeni, J. F. and Hsing, A. W. (2006), CYP17 MspA1 polymorphism and risk of biliary tract cancers and gallstones: A population-based study in Shanghai, China. Int. J. Cancer, 118: 2847–2853. doi: 10.1002/ijc.21708
- Issue online: 14 MAR 2006
- Version of Record online: 27 DEC 2005
- Manuscript Accepted: 18 OCT 2005
- Manuscript Received: 15 SEP 2005
- Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services
- biliary tract cancers;
Biliary tract cancers, encompassing cancers of the gallbladder, extrahepatic bile duct and ampulla of Vater, are rare but highly fatal malignancies. Other than gallstones, little is known about the risk factors for biliary tract cancers. Endogenous estrogens are thought to play a role in the etiology of gallstones and gallbladder cancer, since both conditions predominate in females and are associated with parity and obesity. In view of reports linking the CYP17 MspA1 polymorphism to high circulating levels of estrogens and a predisposition to other hormonally related cancers, we examined the relationship between CYP17 MspA1 variants and risk of biliary disease in a population-based case-control study in Shanghai. The study included 446 cancer cases (254 gallbladder, 139 extrahepatic bile duct, 53 ampullary cancers), 929 biliary stone cases (691 gallbladder, 238 bile duct) and 818 population controls. Genomic DNA from peripheral blood lymphocytes was used for genotyping. Relative to those with the A2/A2 genotype, A1 carriers (A1/A1 and A1/A2 genotypes) had an increased risk of gallbladder cancer (odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1–2.1). In addition, women with the A1 allele and high parity (≥3) had a 3-fold risk of gallbladder cancer (OR = 3.3, 95% CI = 1.6–6.9), compared to those with the A2/A2 genotype and lower parity, with the highest risk seen for those also having biliary stones (OR = 4.6, 95% CI = 1.8–11.7, Pinteraction = 0.04). The A1 allele was not associated with a higher risk of gallstones except among those with body mass index (BMI) greater than 25 kg/m2 (OR = 3.1, 95% CI = 2.0–4.8, Pinteraction = 0.02) and among those with a history of diabetes (OR = 2.5, 95% CI = 1.4–4.3, Pinteraction = 0.09). No clear relation was seen between the CYP17 polymorphism and cancers of the bile duct or ampulla of Vater. The association of the CYP17 MspA1 polymorphism with an increased risk of gallbladder cancer, as well as biliary stones among overweight and diabetic individuals, suggests an interplay between genetic and hormonal risk factors in gallbladder disease. © 2005 Wiley-Liss, Inc.