CYP1B1 gene polymorphism modifies pancreatic cancer risk but not survival
Abstract:
Pancreatic cancer represents one of the biggest problems of current oncology. The risk factors of pancreatic cancer development, as well as factors affecting survival are poorly understood. Since biotransformation enzymes modify detoxification of carcinogens, we supposed, that a relationship between their polymorphism and the risk of pancreatic cancer development and eventually its clinical outcome may exist.Associations of so far not studied cytochrome P450 1B1 (CYP1B1) polymorphisms with pancreatic cancer risk were investigated by case-control study. A total of 754 participants were recruited during study period. All patients were followed to determine their treatment and overall survival.Carriers of rare genotype Val/Val in codon 432 of CYP1B1 (rs1056836) were under significantly lower risk of pancreatic cancer than wild type carriers (p=0.035). Carriers of heterozygous genotype (p=0.033) and rare allele Val (p=0.015) were also under lower risk than wild type carriers. When histology-verified patients were analyzed separately, even more significant associations were found (p=0.016, p=0.009, p=0.003, respectively). On the contrary, CYP1B1 polymorphism in codon 453 (rs1800440) did not significantly associate with pancreatic cancer risk. Median survival of patients with rare homozygous genotype Val/Val in CYP1B1-codon 432 was longer but not significantly different from those with wild-type homozygotes. The same was true for CYP1B1-codon 453 wild-type homozygotes in comparison with Ser/Ser rare homozygotes.CYP1B1 polymorphism in codon 432 seems to modify the risk of pancreatic cancer development and should be further studied.