Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: a population-based study in Shanghai, China.

BACKGROUND AND AIM: 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.