Cholecystokinin receptor A gene polymorphism in gallstone disease and gallbladder cancer

Abstract

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. 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. 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. 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.