TY - JOUR
T1 - Variants in inflammation genes and the risk of biliary tract cancers and stones
T2 - A population-based study in China
AU - Hsing, Ann W.
AU - Sakoda, Lori C.
AU - Rashid, Asif
AU - Andreotti, Gabriella
AU - Chen, Jinbo
AU - Wang, Bin Shen
AU - Shen, Ming Chang
AU - Chen, Bingshu E.
AU - Rosenberg, Philip S.
AU - Zhang, Mingdong
AU - Niwa, Shelley
AU - Chu, Lisa
AU - Welch, Robert
AU - Yeager, Meredith
AU - Fraumeni, Joseph F.
AU - Gao, Yu Tang
AU - Chanock, Stephen J.
PY - 2008/8/1
Y1 - 2008/8/1
N2 - To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003)and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.
AB - To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003)and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.
UR - http://www.scopus.com/inward/record.url?scp=50249125136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50249125136&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-08-0444
DO - 10.1158/0008-5472.CAN-08-0444
M3 - Article
C2 - 18676870
AN - SCOPUS:50249125136
SN - 0008-5472
VL - 68
SP - 6442
EP - 6452
JO - Cancer Research
JF - Cancer Research
IS - 15
ER -