DRUSE

A number of pathways operate to repair DNA damage: nucleotide excision repair (NER), base excision repair (BER), double-strand breaks (DSB), and mismatch repair (MMR).

In a study by David Neasham and colleagues, single nucleotide polymorphisms in 16 DNA repair genes were examined to identify potential predictors of mortality or increased risk of cancer. A healthy population of non-smokers , Gen-Air sub-cohort from European Prospective Investigation into Cancer and Nutrition (EPIC) study, was used. It comprised of 568 men and 520 women (mean age at recruitment 61 years). DNA samples were genotyped by TaqMan Nuclease Assay, except hOGG1-Ser326Cys which was genotyped by the primer extension technique on a denaturing HPLC instrument. A combination of plain TaqMan and fluorogenic MGB (minor groove binder) probes were used. Allele specific probes were labelled with FAM and VIC.

A strong and consistent association between mortality and two DNA repair polymorphisms XRCC3-Thr241Met and XRCC2Arg188His was observed. XRCC3 and XRCC2 belong to the Rad51 family and are thought to mediate homologous pairing and strand exchange during the repair of double-strand breaks.

Citation:

Neasham D, Gallo V, Guarrera S, Dunning A, Overvad K, Tjonneland A, Clavel-Chapelon F, Linseisen JP, Malaveille C, Ferrari P, Boeing H, Benetou V, Trichopoulou A, Palli D, Crosignani P, Tumino R, Panico S, Bueno-De-Mesquita HB, Peeters PH, van Gib CH, Lund E, Gonzalez CA, Martinez C, Dorronsoro M, Barricarte A, Navarro C, Quiros JR, Berglund G, Jarvholm B, Khaw KT, Key TJ, Bingham S, Diaz TM, Riboli E, Matullo G, Vineis P. 2009. Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers. DNA Repair (Amst). 2009 Jan 1;8(1):60-71. Epub 2008 Oct 28.