Polymorphism of genes related to insulin sensitivity and the risk of biliary tract cancer and biliary stone: a population-based case-control study in Shanghai, China.
Biliary tract cancer, encompassing tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, is a rare but highly fatal malignancy. Obesity and gallstones, both related to insulin resistance, are linked to an elevated risk of biliary cancer. The peroxisome proliferator-activated receptors (PPARs) and the retinoid X receptors (RXRs), expressed in adipose tissue, play a key role in the regulation of obesity-related insulin sensitivity, thus genetic variants of these two receptor genes may be related to biliary cancer and stones. We examined the associations of seven single-nucleotide polymorphisms in the PPAR-gamma, PPAR-delta, RXR-alpha, RXR-beta and INS genes with biliary cancer and stones in a population-based case-control study in Shanghai, China. We included 237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater cancer cases, 895 stone cases and 786 population controls. Relative to individuals with the RXR-beta C51T (rs2076310) CC genotype, those having the TT genotype had a 1.6-fold risk for bile duct cancer [odds ratio (OR) = 1.67; 95% confidence interval (CI) = 0.99-2.84], with a more pronounced association among men (OR = 2.30; 95% CI = 1.14-4.65; P interaction = 0.07). This marker was also associated with a higher risk of gallstones among subjects with a higher body mass index (BMI) (>or=23 kg/m(2)) (OR = 1.80; 95% CI = 1.09-2.94), although the interaction with BMI was not statistically significant (P interaction = 0.28). No association was found between other variants and biliary cancers and stones. Results from this population-based study suggest that certain genetic variants involved in the regulation of obesity-related insulin sensitivity may increase susceptibility to bile duct cancer and gallstones.
Chang
Shih-Chen
SC
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
Rashid
Asif
A
Gao
Yu-Tang
YT
Andreotti
Gabriella
G
Shen
Ming-Chang
MC
Wang
Bin-Sheng
BS
Han
Tian-Quan
TQ
Zhang
Bai-He
BH
Sakoda
Lori C
LC
Leitzmann
Michael F
MF
Chen
Bingshu E
BE
Rosenberg
Philip S
PS
Chen
Jinbo
J
Chanock
Stephen J
SJ
Hsing
Ann W
AW
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005706:Gallbladder Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D042882:Gallstones / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000235:genetics*; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics; D011110:Polymorphism, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D012307:Risk Factors
D004273:DNA, Neoplasm; D007328:Insulin; D047495:PPAR gamma; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082925:retinoic acid receptor beta