This Article Full Text Full Text (PDF) All Versions of this Article: 1055-9965.EPI-07-2704v1 17/3/525    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Andreotti, G. Articles by Hsing, A. W. Search for Related Content PubMed PubMed Citation Articles by Andreotti, G. Articles by Hsing, A. W.

Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services; ² Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania; ³ Department of Epidemiology, Shanghai Cancer Institute; ⁴ Department of Pathology, M. D. Anderson Cancer Center, Houston, Texas; ⁵ Department of Epidemiology, University of Washington, Washington; ⁶ Shanghai Tumor Hospital and ⁷ Zhongshan Hospital, Fudan University; ⁸ Department of Surgery, Ruijin Hospital, Second Medical University; ⁹ Institute of Oriental Hepatobiliary Surgery, Second Military University, Shanghai, China; ¹⁰ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and ¹¹ Core Genotyping Facility, National Cancer Institute, NIH, Gaithersburg, Maryland

Requests for reprints: Gabriella Andreotti, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, 6120 Executive Boulevard, EPS 8011, MSC 7240, Bethesda, MD 20892. Phone: 301-594-7902; Fax: 301-402-1819. E-mail: andreotg{at}mail.nih.gov

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by TaqMan assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% CI), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% CI, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% CI, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% CI, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct. (Cancer Epidemiol Biomarkers Prev 2008;17(3):525–34)