Contribution of the genetic polymorphisms to cancer risk in chronically exposed individuals

The objective of the current research is to evaluate the contribution of the genetic factor to the risk of cancer development in the individuals affected by chronic low dose-rate exposure on the Techa River. Materials and Methods: The study of the relationship between the polymorphic loci of the genes regulating cell cycle and apoptosis with the risk of cancer development involved 922 members of the Southern Urals Population Exposed to Radiation cohort. Real-time PCR was used to perform the genotyping of polymorphic loci. Results and Discussion: A statistically significant relationship of the alleles rs2279744*С of the gene MDM2 and rs2279115*С of the gene BCL-2 with the increased risk of cancer development has been established (odds ratio = 1.75; confidence interval 95 % [1.15-2.65]; p=0.008 and odds ratio = 1.63; confidence interval 95 % [1.21-2.21]; p=0.001 respectively). Single nucleotide polymorphism that is associated with a decreased risk of cancer development has also been revealed: the allele rs1801270*А of the gene CDKN1A (odds ratio = 0.62; confidence interval 95 % [0.44-0.88]; p=0.007). The analysis of gene interaction factor and absorbed dose to the red bone marrow determined the most statistically significant model that includes the dose to the red bone marrow, NFkB rs28362491, ATM rs664677, BCL2 rs2279115, MDM2 rs2279744 (repeatability is 10 out of 10, accuracy 62 %; p=0.04). Polymorphism rs2279744 of the gene MDM2 is the greatest information contributor (2.43 %). Conclusion: Single nucleotide polymorphisms of the genes encoding cell cycle and cell death enzymes are capable of modifying cancer development risk.