title: Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China.
abstract: 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics and Office of Preventive Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892-7234, USA. hsinga@mail.nih.gov
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Lori C
authors.initials: LC
authors.lastname: Sakoda
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Gabriella
authors.initials: G
authors.lastname: Andreotti
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.forename: Bin-Shen
authors.initials: BS
authors.lastname: Wang
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Shen
authors.forename: Bingshu E
authors.initials: BE
authors.lastname: Chen
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Mingdong
authors.initials: M
authors.lastname: Zhang
authors.forename: Shelley
authors.initials: S
authors.lastname: Niwa
authors.forename: Lisa
authors.initials: L
authors.lastname: Chu
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
mesh_terms: D001661:Biliary Tract Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002681:China; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012307:Risk Factors