Association of genetic variants of xenobiotic and estrogen metabolism pathway (CYP1A1 and CYP1B1) with gallbladder cancer susceptibility.

[carcinoma of the gallbladder]

Gallbladder carcinoma is a highly aggressive cancer with female predominance . Interindividual differences in the effectiveness of the activation /detoxification of environmental carcinogens and endogenous estrogens may play a crucial role in cancer susceptibility . The present study included 410 patients with carcinoma of the gallbladder (GBC ) and 230 healthy subjects . This study examined association of CYP 1 A 1 -MspI , CYP 1 A 1 -Ile 462 Val , and CYP 1 B 1 -Val 432 Leu with GBC susceptibility . CYP 1 A 1 -MspI [CC ] and CYP 1 A 1 -Ile 462 Val [iso /val ] genotypes were found to be significantly associated with GBC (p =0 .006 and p =0 .03 , respectively ), as compared to healthy controls , while CYP 1 B 1 -Val 432 Leu was not associated with GBC . The CYP 1 A 1 haplotype [C-val ] showed a significant association with GBC (p =0 .006 ). On stratification based on gender , the CYP 1 A 1 -MspI [CC ] genotype showed an increased risk of GBC in females (p =0 .018 ). In case-only analysis , tobacco users with CYP 1 A 1 -MspI [CT ] genotypes were at a higher risk of GBC (p =0 .008 ). Subdividing the GBC patients on the basis of gallstone status , the CYP 1 A 1 haplotype [C-val ] imparted a higher risk in patients without stones when compared to controls (p =0 .001 ). The results remained significant even after applying Bonferroni correction . Multivariate analysis revealed an increased risk of CYP 1 A 1 iso /val and val /val genotypes in GBC patients having BMI >25 (p =0 .021 ). The CYP 1 A 1 polymorphisms may confer increased risk of GBC , probably due to impaired xenobiotic or hormone metabolism through a gallstone-independent pathway .