Cholecystokinin receptor A gene polymorphism in gallstone disease and gallbladder cancer

Background and Aim:  Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease which may be causatively related to decreased gallbladder contractility. Cholecystokinin receptor A ( CCK-AR ) mediates signals resulting in gallbladder contraction. Deteriorating gallbladder contraction promotes gallstone formation. A common genetic polymorphism of CCK-AR may be causatively associated with the risk of gallstone and GBC. This study aimed to understand the association of CCK-AR Pst I polymorphism in gallstone disease with gallbladder cancer.
Method:  This study included 165 gallstone patients, 139 GBC patients, and 190 healthy subjects. Genotyping was done using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method.
Results:  The frequency of the A1A1 genotype of CCK-AR was significantly higher in gallstone patients than healthy individuals ( P  = 0.008 odds ratio OR] = 2.25, and 95% confidence interval CI]:1.2–4.1). However, there was a significant difference in the frequency of A1A1 genotype when gallstone patients were compared to GBC patients ( P  = 0.041, OR = 0.49, and 95% CI: 0.3–0.9). On stratification of GBC patients according to presence or absence of gallstones, GBC patients without stones were compared to controls and GBC patients with stones were compared to stone patients; however, no significant differences in frequencies were observed.
Conclusion:  The results suggest that the A1A1 genotype of CCK-AR is an independent genetic risk factor for gallstone disease and does not modulate the susceptibility of gallbladder cancer.