Chronic oxidative stress, a likely cancer risk factor, can induce DNA damage by the formation of exocyclic DNA adducts, such as 1,N2-propanodeoxyguanosine. It is formed either directly from trans-4-hydroxy-2-nonenal or during degradation of fatty acid peroxides. This specific biomarker for oxidative stress induced by lipid peroxidation can be measured in peripheral blood lymphocytes. DNA adduct levels, however, can be modulated by dietetic antioxidants and vitamins or by genetic susceptibility factors such as cellular DNA repair. Here, we determined 1,N2-propanodeoxyguanosine levels in DNA of peripheral blood lymphocytes of 278 healthy individuals, who took part in the “Bavarian Food Consumption Survey II”. In this representative population study detailed information was collected about nutritional habits and lifestyle factors. As 1,N2-propanodeoxyguanosine is removed by nucleotide excision repair (Johnson et al., 1997), we determined genetic polymorphisms in DNA excision repair genes (XPD/ERCC2, Lys751Gln and Asp312Asn, and XPA, -4G/A), as possible indicators of individual DNA repair activity. Associations of DNA adduct levels with genotypes were determined by logistic regression analysis. Various confounding factors such as socio-economic factors and vitamin intake were taken into account in the analysis and were shown to affect adduct levels. After adjustment, we found an increased risk for an elevated adduct level in individuals carrying the A allele of the XPA gene (adjusted OR: 2.47; CI 1.05-5.80). No such correlation was found for the two XPD polymorphisms. The A allele of the XPA gene was reported to reduce DNA repair capacity (Wu et al., 2003) and to be a risk allele for various cancer types. Thus, our data infer that 1,N2-propanodeoxyguanosine adduct levels are modulated not only by lifestyle and nutritional factors but also by the individual DNA repair capacity. Further investigations are necessary to establish which other gene variants are modifiers of endogenous DNA damage and susceptibility for cancers at specific sites.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]