Association of adrenergic receptor gene polymorphisms in gallbladder cancer susceptibility in a North Indian population

Gallbladder cancer (GBC), the most common gastrointestinal and biliary tract malignancy, often coincides with gallstone disease (GSD). The genetic variants of adrenergic receptor (ADR) have been previously reported to be associated with hypomotility disorder of cardiovascular system and GSD. Since GSD may function as GBC precursor, the present study aimed to investigate the association of common functional genetic variants of ADRA2A C-1291G, ADR beta 3 T190C or Trp64Arg, and ADR beta 1 C1165G or Arg389Gly with GBC and GSD susceptibility. The present study included a total of 400 histologically confirmed GBC, 230 GSD, and 268 healthy controls. The ADRA2A C-1291G, ADR beta 3 T190C, and ADR beta 1 C1165G polymorphisms were determined by PCR-RFLP. Statistical analysis was performed by using SPSS version 16. ADR beta 3 T190C polymorphism was significantly associated with increased risk of GBC (CT: Pcorr = 0.015, OR 2.87; CC: Pcorr = 0.038, OR 10.33; C allele: Pcorr = 0.014, OR 2.7; CT + CC: Pcorr = 0.017, OR 3.05). These associations existed even after gallstone and gender stratification. Similarly, ADR beta 3 T190C polymorphism was also associated with GSD risk, though limited only to female GSD patients. In contrary, ADRA2A C-1291G conferred a marginally increased risk only in GSD patients. ADR beta 1 C1165G polymorphism was not associated with GBC and GSD susceptibility when compared to controls. ADR beta 3 T190C polymorphism is significantly associated with GBC and GSD susceptibility. The ADR beta 3 T190C may be involved in the pathophysiology of GBC by both gallstone-dependent pathway and by some other independent mechanisms.