title: Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: a population-based study in Shanghai, China.
abstract: OBJECTIVE
  Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones.
  
  
  METHODS
  We investigated the associations between nine single nucleotide polymorphisms in CCK and CCKAR in a population-based case-control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct, and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in Shanghai, China.
  
  
  RESULTS
  We found that women with the CCKAR rs1800855 AA genotype had an increased risk of gallbladder cancer (odds ratio = 2.37, 95% confidence interval (CI): 1.36-4.14) compared with subjects with the TT genotype, and remained significant after Bonferroni correction (P = 0.0056). Additionally, female carriers of the CCKAR haplotype C-T-C-T (rs2071011-rs915889-rs3822222-rs1800855) had a reduced risk of gallbladder cancer (odds ratio = 0.61, 95% confidence interval: 0.43-0.86) compared with those with the G-C-C-A haplotype; the association also remained significant after Bonferroni correction.
  
  
  CONCLUSIONS
  These findings suggest that variants in the CCKAR gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Xu
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Emily
authors.initials: E
authors.lastname: Vogtmann
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Chu
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Tan
authors.forename: Bing-Sheng
authors.initials: BS
authors.lastname: Wang
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Shen
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D001661:Biliary Tract Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002766:Cholecystokinin / Q000235:genetics*; D005260:Female; D042882:Gallstones / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043886:Receptor, Cholecystokinin A / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D012737:Sex Factors
chemical_list: D043886:Receptor, Cholecystokinin A; D002766:Cholecystokinin
keywords: CCK and CCKAR; biliary tract cancer; gallstone; haplotype; susceptibility; variant