The Role of Polymorphisms of Key Genes of DNA Base Excision Repair in Terms of Lung Cancer Predisposition in "Mayak" Workers.

Abstract

An association between polymorphic variants of key genes of base excision repair (BER) and lung cancer was studied in "Mayak" workers occupationally exposed to prolonged external y-rays and internal α-radiation from incorporated (239)Pu. The study was "case-control". The group of "cases" consists of 75 "Mayak" workers with the verified diagnosis of "lung cancer". At the moment of diagnosis the mean total absorbed dose from external y-rays to whole body was 1.19 Gy; the mean total absorbed dose from internal α-radiation due to incorporated (239)Pu in lung was 0.31 Gy. The group of "controls" includes "Mayak" workers matched by sex and birth year without lung cancer and other cancers during the study period (141 individuals). Increased lung cancer risk was revealed in workers-carriers of homozygous minor genotype of genes OGG] Ser326Cys (OR - 4.67, p = 0.007), APEI Asp148Glu (OR = 1.82, p = 0.063) and XRCC1 Gln399Arg (OR = 2.86, p = 0.026). Increased lung cancer risk was revealed in carriers of different pairwise combinations of minor genotypes of the studied genes of BER or in carriers of pairwise combinations with one homozygous minor mm-genotype and the other homozygous major ww genotype. Thus, OR of lung cancer in carriers of pairwise genotypes of mm genes OGG] Ser326Cys and APE] Asp 148Glu was 12.17.