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.
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.
Andreotti
Gabriella
G
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, USA. andreotg@mail.nih.gov
Chen
Jinbo
J
Gao
Yu-Tang
YT
Rashid
Asif
A
Chen
Bingshu E
BE
Rosenberg
Philip
P
Sakoda
Lori C
LC
Deng
Jie
J
Shen
Ming-Chang
MC
Wang
Bing-Sheng
BS
Han
Tian-Quan
TQ
Zhang
Bai-He
BH
Yeager
Meredith
M
Welch
Robert
R
Chanock
Stephen
S
Fraumeni
Joseph F
JF
Hsing
Ann W
AW
D000328:Adult; D000368:Aged; D000483:Alleles; D001661:Biliary Tract Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D042882:Gallstones / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007407:Interviews as Topic; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors
D014408:Biomarkers, Tumor