Mouse Anti Human APEX Nuclease I Hybridoma [DQUD-BQFY2-3]

Breast-conserving surgery followed by radiotherapy is effective in reducing recurrence; however, telangiectasia and fibrosis can occur as late skin side effects. As radiotherapy acts through producing DNA damage, we investigated whether genetic variation in DNA repair and damage response confers increased susceptibility to develop late normal skin complications. Breast cancer patients who received radiotherapy after breast-conserving surgery were examined for late complications of radiotherapy after a median follow-up time of 51 months. Polymorphisms in genes involved in DNA repair (APEX1, XRCC1, XRCC2, XRCC3, XPD) and damage response (TP53, P21) were determined. Associations between telangiectasia and genotypes were assessed among 409 patients, using multivariate logistic regression. A total of 131 patients presented with telangiectasia and 28 patients with fibrosis. Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia. The odds ratios (OR) were 1.66 (95% confidence interval (CI): 1.02-2.72) for 72Pro carriers and 1.95 (95% CI: 1.13-3.35) for PIN3 A2 allele carriers compared with non-carriers. The TP53 haplotype containing both variant alleles was associated with almost a two-fold increase in risk (OR 1.97, 95% CI: 1.11-3.52) for telangiectasia. Variants in the TP53 gene may therefore modify the risk of late skin toxicity after radiotherapy. British Journal of Cancer (2009) 100, 1680-1686. doi: 10.1038/sj.bjc.6605036 www.bjcancer.com Published online 14 April 2009 (C) 2009 Cancer Research UK

Background: Enhanced generation of reactive oxygen species and increased oxidative-induced DNA damage have been identified as possible contributors to atherosclerosis. The base excision repair (BER) pathway is the principal mechanism by which mammalian cells repair oxidative DNA damage. BER deficiency can potentially accelerate atherogenesis. Methods: We evaluated the association of Single Nucleotide Polymorphisms (SNPs) in genes encoding four different BER proteins (NEIL3, OGG1, APEX1 and XRCC1) with the incidence of myocardial infarction in a nested case control study among participants of the second survey of the HUNT Study. The study population included 1624 cases and 4087 age- and sex-matched controls. Results: For the NEIL3 SNP rs12645561, the TT genotype was associated with increased risk of MI (OR 1.47, 95% CI 1.02-2.12, p uncorrected for multiple comparisons = 0.04) both in the genotypic test (compared to the CC genotype) and in the recessive genetic model (compared to the CC and CT genotypes combined). For the other two NEIL3 SNPs (rs10013040 and rs1395479) and for the SNPs of OGG1 (rs1052133),APEX1 (rs1878703) and XRCC1 (rs25489) we observed no association with risk of myocardial infarction. Conclusion: We found that the NEIL3 rs12645561 SNP TT genotype was associated with increased risk of myocardial infarction. If confirmed in other studies, this association may suggest a possible role of attenuated DNA repair, and NEIL3 in particular, in atherogenesis. (C) 2015 Elsevier B.V. All rights reserved.