TY - JOUR
T1 - Polymorphism of genes related to insulin sensitivity and the risk of biliary tract cancer and biliary stone
T2 - A population-based case-control study in Shanghai, China
AU - Chang, Shih Chen
AU - Rashid, Asif
AU - Gao, Yu tang
AU - Andreotti, Gabriella
AU - Shen, Ming Chang
AU - Wang, Bin Sheng
AU - Han, Tian Quan
AU - Zhang, Bai He
AU - Sakoda, Lori C.
AU - Leitzmann, Michael F.
AU - Chen, Bingshu E.
AU - Rosenberg, Philip S.
AU - Chen, Jinbo
AU - Chanock, Stephen J.
AU - Hsing, Ann W.
N1 - Funding Information:
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20892, USA, 2Department of Pathology MD Anderson Cancer Center, Houston, TX 77030, USA, 3 Department of Epidemiology Shanghai Cancer Institute, Shanghai, China, 4Shanghai Tumor Hospital, Shanghai, China, 5Zhongshan Hospital, Shanghai, China, 6Rui-jian Hospital, Shanghai, China, 7Oriental Hepato-biliary Surgery Hospital, Shanghai, China, 8Department of Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA 19104, USA, 9Core Genotyping Facility, National Cancer Institute, Gaithersburg, MD 20877, USA and 10Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA *To whom correspondence should be addressed. Tel: +1 301 496 1691; Fax: +1 301 401 0916; Email: hsinga@mail.nih.gov
PY - 2008/5
Y1 - 2008/5
N2 - 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-γ, PPAR-δ, RXR-α, RXR-β 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-β 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) (≥23 kg/m2) (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.
AB - 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-γ, PPAR-δ, RXR-α, RXR-β 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-β 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) (≥23 kg/m2) (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.
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U2 - 10.1093/carcin/bgn025
DO - 10.1093/carcin/bgn025
M3 - Article
C2 - 18375961
AN - SCOPUS:47249092818
SN - 0143-3334
VL - 29
SP - 944
EP - 948
JO - Carcinogenesis
JF - Carcinogenesis
IS - 5
ER -