Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Abstract

Sixteen candidate polymorphisms (13 SNPs and 3 microsatellites) in nine genes from four DNA repair pathways were examined in 83 subjects, comprising 23 survivors of childhood cancer, their 23 partners, and 37 offspring, all of whom had previously been studied for G 2 chromosomal radiosensitivity. Genotype at the Asp148Glu SNP site in the APEX gene of the base excision repair (BER) pathway was associated with childhood cancer in survivors (P = 0.001, significant even after multiple test adjustment), due to the enhanced frequency of the APEX Asp148 allele among survivors in comparison to that of their partners. Analysis of variance (ANOVA) of G 2 radiosensitivity in the pooled sample, as well as family-based association test (FBAT) of the family-wise data, showed sporadic suggestions of associations between G 2 radiosensitivity and polymorphisms at two sites (the Thr241-Met SNP site in the XRCC3 gene of the homologous recombinational pathway by ANOVA, and the Ser326Cys site in the hOGG1 gene of the BER pathway by FBAT analysis), but neither of these remained significant after multiple-test adjustment. This pilot study provides an intriguing indication that DNA repair gene polymorphisms may underlie cancer susceptibility and variation in radiosensitivity. Environ. Mol. Mutagen. 48:48-57, 2007.

Association of XRCC3 and XRCC4 gene polymorphisms, family history of cancer and tobacco smoking with non-small-cell lung cancer in a Chinese population: a case–control study

“…28 Another study showed that rs861539 was associated with G2 chromosomal radiosensitivity and could have a protective role in cancer susceptibility. 29 However, the same group 4 years later failed to repeat their previous data on the association between rs861539 and cancer risk or G(2) chromosomal radiosensitivity. 30 Meta-analysis 19,31 studies concluded that this SNP might have not been associated with lung cancer risk.…”

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

“…Assays that have shown promise include colony survival assays (Brock et al, 1995;West et al, 1998), chromosomal aberration frequency (Neubauer et al, 1997(Neubauer et al, , 2002Distel et al, 2006), comet assay (Brammer et al, 2001), DNA damage and repair based on pulsedfield gel electrophoresis (PFGE) (Wurm et al, 1994;McKay and Kefford, 1995;Zhou et al, 1998), micronucleus assay (Nachtrab et al, 1998;Sprung et al, 2005), telomere length (McIlrath et al, 2001;Sprung et al, 2008), SNP analysis (Severin et al, 2001;Gurska et al, 2007;Wilding et al, 2007;Alsner et al, 2008), DNA end binding complexes (Ismail et al, 2004) and transcriptional profiling (Rieger et al, 2004;Svensson et al, 2006;Sprung et al, in preparation). Thus, many potential endpoints exist, most of which have been partially successful in identifying clinical RS.…”

XRCC3 Polymorphisms are Associated with the Risk of Developing Radiation-induced Late Xerostomia in Nasopharyngeal Carcinoma Patients Treated with Intensity Modulation Radiated Therapy

“…Single-nucleotide polymorphisms (SNPs) in DNA repair genes may alter protein function and individual's capacity to repair damaged DNA, by which influence individual radiosensitivity and the risk of developing radiation-induced toxicities (9). In current view, normal tissue reactions exhibited after RT were determined by a multifactorial trait resulted from the combined effects of clinical, tumor, treatment and genetic factors (10,11).…”