Genetic susceptibility to renal cell carcinoma: the role of DNA double-strand break repair pathway
Saturday, 25 October 2008 - Alterations in DNA repair genes have been shown to cause a reduction in host DNA repair capacity and may influence host susceptibility to carcinogenesis. The double-strand break repair is a major DNA-repair pathway. Margulis et al. (2008) tested the hypothesis that common sequence variants of the double-strand break pathway genes predispose susceptible individuals to an increased risk for renal cell carcinoma. Toward this end, the authors evaluated the associations of 13 single-nucleotide polymorphisms in 10 candidate genes involved in the double-strand break pathway with renal cell carcinoma risk in a population-based case-control study that included 326 Caucasian renal cell carcinoma patients and 335 controls.
Using the homozygous wild type as the reference group, the authors observed a significantly increased renal cell carcinoma risk associated with the homozygous variant genotype of NBS1 (rs1805794; odds ratio, 2.13; 95% confidence interval (95% CI), 1.17-3.86). Carrying of at least one copy of the variant XRCC4 allele was also associated with a significantly increased risk (rs1805377; odds ratio, 1.56; 95% CI, 1.08-2.26). Importantly, in pathway analysis, compared with the reference group (1 or less adverse alleles), individuals with two (odds ratio, 1.26; 95% CI, 0.83-1.91), three (odds ratio, 1.00; 95% CI, 0.64-1.56), and more than three adverse alleles (odds ratio, 1.75; 95% CI, 1.03-2.98) were at increased risk for renal cell carcinoma with significant association in subjects carrying more than 3 adverse alleles.
In conclusion, individuals with a higher number of genetic variations in the DBS repair pathway are at an increased risk for renal cell carcinoma. These findings require further validation in independent populations.
Margulis, V., Lin, J., Yang, H., Wang, W., Wood, C. G., & Wu, X. (2008). Genetic susceptibility to renal cell carcinoma: the role of DNA double-strand break repair pathway. Cancer Epidemiol Biomarkers Prev, 17(9), 2366-2373.