Bladder cancer genetic risk factors

Pavlov V.N., Izmaylov A.A., Viktorova T.V., Izmaylova S.M., Galimzyanov V.Z., Ahmadishina L.Z.

A bladder cancer (BC) – oncologic disease with wide range of risk factors. A trigger of the most of oncological diseases is an individual genetic predisposition provoked by various environmental factors, first of all of chemical nature. Various cancer causing agents that are collectively known as xenobiotics refer to the risk factors for BC. Necessary condition for manifestation of xenobiotics action is a hypersusceptibility that appears in the presence of certain genetic background. In case of unfavorable genotypes combination the risk of bladder cancer increases.

For the purpose of disclosure of potential associations between polymorphous variants of cytochrome P450 and glutatione-S-transferase enzymes genes, DNA repair gene and bladder cancer development an analysis for frequency of genotypes and polymorhpous gene loci alleles CYP1A1 (Ile462Val), GSTM1 (del), GSTP1 (Ile105Val), XRCC1 (Arg280His) was performed in patients with bladder cancer (n = 146) and in individuals with no cancer detected (n = 241).

It was established that genetic markers of the risk of bladder cancer are genotypes Ile/Val (OR=8.8) and Val/Val (OR=9.1) of CYP1A1 gene, genotype Val/Val of GSTP1 gene (OR=3.0) and genotype His/His (OR=3.7) of XRCC1 gene. There was no significant difference in distribution of gene GSTM1 genotypes frequency among samples of patients and healthy individuals. Presented data gives evidence of important role of xenobiotics detoxication enzymes and DNA repair enzymes in bladder cancer development. In respect that an increased risk of bladder cancer is associated with presense of certain pro-oxidant and antioxidant enzymes gene allelic variants it may be suggested that P450 cytochromes and glutatione-dependent enzymes as well as DNA repair genes may be an important component of genetis predisposition for BC development.