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

Gabriella Andreotti, Jinbo Chen, Yu Tang Gao, Asif Rashid, Bingshu E. Chen, Philip Rosenberg, Lori C. Sakoda, Jie Deng, Ming Chang Shen, Bing Sheng Wang, Tian Quan Han, Bai He Zhang, Meredith Yeager, Robert Welch, Stephen Chanock, Joseph F. Fraumeni, Ann W. Hsing

Research output: Contribution to journalArticle

Abstract

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 Taq-Man 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.

Original languageEnglish (US)
Pages (from-to)525-534
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume17
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Andreotti, G., Chen, J., Gao, Y. T., Rashid, A., Chen, B. E., Rosenberg, P., Sakoda, L. C., Deng, J., Shen, M. C., Wang, B. S., Han, T. Q., Zhang, B. H., Yeager, M., Welch, R., Chanock, S., Fraumeni, J. F., & Hsing, A. W. (2008). 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. Cancer Epidemiology Biomarkers and Prevention, 17(3), 525-534. https://doi.org/10.1158/1055-9965.EPI-07-2704