Effects of the XRCC1 gene‐environment interactions on DNA damage in healthy Japanese workers

Abstract

X-ray repair crosscomplementing group 1 (XRCC1) has a central role in base excision repair (BER) and single-strand break repair (SSBR). XRCC1 gene polymorphisms (codons 194, 280, and 399) have been identified, and in some cases have been reported to contribute to variations in DNA repair capacity and susceptibility to cancer. To further characterize the effects of XRCC1 gene polymorphisms and their possible interactions with environmental factors on individual levels of DNA damage, we investigated the XRCC1 genotypes of 222 healthy Japanese workers and analyzed data with respect to smoking, drinking habits, age, and health practice index (HPI). Our results showed that poor HPI would associate with a higher level of tail moment (TM). Individuals with one or two XRCC1(R280H) variant alleles exhibited significantly higher TM values, and these differences were enhanced by alcohol consumption and aging, whereas smoking and poor HPI may cover up the differences. On the other hand, using a stratified analysis, we found that the XRCC1(R194W) variant was associated with a higher TM value in the 40-50 year-old age group, and the XRCC1(R399Q) variant was associated with a lower TM value in the < or =20 pack-years group or in the 40-50 year-old age group. These data suggest that XRCC1 polymorphisms could influence individual DNA repair capacity by interacting with lifestyle factors, and specifically, the data indicated that the XRCC1(R280H) allele may be more important than codon 194 or 399 alleles.

Genotoxic biomonitoring of tobacco farmers: Biomarkers of exposure, of early biological effects and of susceptibility

“…Polymorphisms affecting fundamental cellular processes responsible for maintaining the genomic integrity, such as DNA repair, could be expected to have this kind of effect [80]. Studies demonstrated that environmental exposures may down-regulate expression of some DNA repair genes for XRCC1 [81]. However, these results are more likely due reduced samples observed in non-exposed group.…”

“…In our study, non-exposed group presented increased association between XRCC4 Ile/Ile and NPB, and between RAD51 G/C or C/C and MN. Maybe these variants could influence individual DNA repair capacity by interacting with lifestyle factors in healthy subjects [81]. Polymorphisms affecting fundamental cellular processes responsible for maintaining the genomic integrity, such as DNA repair, could be expected to have this kind of effect [80].…”

Functional capacity of XRCC1 protein variants identified in DNA repair-deficient Chinese hamster ovary cell lines and the human population

“…Such results are seemingly consistent with past complementation experiments, in which two out of three studies have found that R280H exhibits an impaired biological function (52–54). Moreover, a few investigations have found that the R280H variant of XRCC1, in contrast to variants R194W or R399Q, imparts a reduced DNA repair capacity phenotype as assessed by the Comet assay (55,56). Thus, although there are mixed reports on R280H, our data supports the evidence that the R280H genotype is more likely a negative risk factor than R194W and R399Q in disease susceptibility, possibly due to a defect in DNA binding.…”

XRCC1 Arg399Gln and Arg194Trp polymorphisms in prostate cancer risk: a meta-analysis

“…The base excision repair pathway mainly removes non-bulky base adducts produced by methylation, oxidation or reduction by ionizing radiation or oxidative damage. Several studies [46][47][48] suggested a possible interaction between XRCC1 polymorphisms and environmental factors on cancer risk. The gene-environment interactions have been of great interest to evaluate the exact roles of genetic polymorphisms.…”