Genotype-phenotype Relationship between DNA Repair Gene Genetic Polymorphisms and DNA Repair Capacity

Genotype-phenotype relationships between genetic polymorphisms of DNA repair genes and DNA repaircapacity were evaluated in a case-control study of breast cancer. Selected DNA repair genes included were thoseinvolved in double-strand break repair (ATM, XRCC2, XRCC4, XRCC6, LIG4, RAD51, RAD52), base excisionrepair (LIG1), nucleotide excision repair (ERCC1), and mismatch repair (hMLH1). The subjects consisted ofhistologically confirmed breast cancer cases (n=132) and controls (n=75) with no present or previous history ofcancer. Seventeen single nucleotide polymorphisms of 10 genes (ATM -5144A>T, IVS21+1049T>C, IVS33-55T>C,IVS34+60G>A, and 3393T>G, XRCC2 31479G/A, XRCC4 921G/T, XRCC6 1796G/T, LIG4 1977T/C, RAD51135G/C, 172G/T, RAD52 2259C/T, LIG1 583A/C, ERCC1 8092A/C, 354C/T, hMLH1 5’ region -93G/A, 655A/G)were determined by TaqMan assay (ATM) or MALDI-TOF (all other genes). DNA repair capacity was measuredby a host cell reactivation assay of repair of ultraviolet damage. The DNA repair capacity (%) did not differbetween cases (median 37.2, interquartile range: 23.6-59.6) and controls (median 32.7, interquartile range:26.7-53.2). However, DNA repair capacity significantly differed by the genotypes of ATM and RAD51 genesamong cancer-free controls. Our findings suggest that DNA repair capacity might be influenced by geneticpolymorphisms of DNA damage response genes and DNA repair genes.