Background: Genetic variation in genes involved in steroid biosynthesis, metabolism and signal transduction have been suggested to play a role in gallstone disease.
Methods: To elucidate the possible role of genetic variation in the estrogen receptors alpha and beta (ER-alpha, ER-beta) and androgen receptor (AR) genes in breast cancer risk, the -1174(TA)n, c.1092+3607(CA)(n) and c.172(CAG)n repeat polymorphisms of the three genes were studied. A case-control cohort of 99 patients with cholelithiasis and 179 controls were used.
Results: No significant difference was observed in the frequency distribution of -1174(TA)(0-26) in the ER-alpha gene between patients and controls, while a significant difference was observed in the frequency distribution of repeat polymorphism c.1092+3607(CA)5-27 and c.172(CAG)5-32 in the ER-beta gene and AR gene, respectively (P< or =0.001 and P=0.05, respectively). A significant difference was observed in the repeat genotype distribution (SS, SL, LL) in the (CA)n of the ER-beta gene (P<0.0001) and in the (CAG)n of the AR gene (P< or =0.0001). A significantly decreased odds ratio for cholelithiasis risk was observed in individuals having the SL and LL genotype for ER-beta gene compared with SS genotype (OR=0.212; 95% CI 0.105-0.426; P<0.0001 and OR=0.042; 95% CI 0.018-0.097, respectively) and LL genotype for AR gene (OR=0.622; 95% CI 0.345-1.121; P=0.114 and OR=0.287; 95% CI 0.151-0.543, P<0.0001, respectively). This protective effect of SL and LL genotypes for ER-beta and LL for AR gene remained evident (P<0.0001 for all of them) even after adjustment for various risk factors.
Conclusions: In conclusion an association for cholelithiasis risk between short alleles for both c.1092+3607(CA)5-27 and c.172(CAG)5-32 repeat polymorphisms of the ER-beta and AR was found in individuals of Greek descent.