Abstract
BackgroundGenetic variants in inflammation-related genes have been associated with biliary stones and biliary tract cancers in previous studies.MethodsTo follow-up on these findings, we examined 35 single nucleotide polymorphism (SNPs) in 5 genes related to inflammation (IL8, NFKBIL, RNASEL, TNF, and VEGFA) in 456 participants with incident biliary tract cancer cases (262 gallbladder, 141 extrahepatic bile duct, 53 ampulla of Vater), 982 participants with biliary stones, and 860 healthy controls in a population–based case–control study in Shanghai, China.ResultsSuggestive associations were observed for SNPs in VEGFA with biliary stones, IL8 with gallbladder and ampulla of Vater cancers, and RNASEL with ampulla of Vater cancer (false discovery rate≤0.2).ConclusionThese findings provide additional support for the role of inflammation in biliary stones and biliary tract cancer risk and need further validation.
Highlights
Genetic variants in inflammation-related genes have been associated with biliary stones and biliary tract cancers in previous studies
Of the 35 SNPs examined, statistically significant (p
We extended the analysis of common genetic variants to approximately 80% coverage for VEGFA, 90% for RNASEL and 75% for IL8, none of the overall effects for each of the tested genes resulted in significant associations at the 0.05 level with either biliary stones or cancer
Summary
Genetic variants in inflammation-related genes have been associated with biliary stones and biliary tract cancers in previous studies. Previous clinical and population-based studies have linked various inflammatory factors and mechanisms with the development of biliary tract cancers [3,4,5,6]. Data from our population-based study of biliary tract cancers in Shanghai suggested that variants in PTGS2 [10], IL8, IL8RB, RNASEL, NOS2 and VEGF were associated with biliary tract cancer and/or stones [11]. To follow-up on these initial findings, in this analysis we examined an additional 28 SNPs in four of the candidate genes we previously identified (IL8, RNASEL, TNF, and VEGFA) in our population-based study in Shanghai. We evaluated five SNPs in NFKBIL, a novel gene in the major histocompatibility complex (MHC) class I region that was not evaluated previously
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