XRCC1 R399Q polymorphism and risk of normal tissue injury after radiotherapy in breast cancer patients
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Radiotherapy is an important weapon in the treatment of breast cancer, but normal tissue injury after radiotherapy can be a threat for patients. Genetic markers conferring the ability to identify hyper-sensitive patients at risk of normal tissue injury in advance would considerably improve therapy. Association studies on genetic variation and occurrence of normal tissue injury can help us identify such markers, but previous studies on the association between XRCC1 R399Q polymorphism and risk of normal tissue injury after radiotherapy in breast cancer patients report conflicting findings. We performed a meta-analysis to comprehensively evaluate the association between XRCC1 R399Q polymorphism and risk of normal tissue injury after radiotherapy in breast cancer patients. The pooled odds ratios (ORs) with their 95 % confidence interval (95 % CIs) were calculated to assess the strength of the association. Fourteen case–control studies with a total of 2,448 breast cancer cases were finally included into the meta-analysis. Overall, XRCC1 R399Q polymorphism was significantly associated with increased risk of normal tissue injury after radiotherapy under all three models (for QQ versus RR: fixed-effects OR = 1.06, 95 % CI 1.00–1.13, P = 0.050; for RQ versus RR: fixed-effects OR = 1.05, 95 % CI 1.00–1.10, P = 0.047; for QQ/RQ versus RR: fixed-effects OR = 1.26, 95 % CI 1.01–1.58, P = 0.041). The meta-analysis suggests that XRCC1 R399Q polymorphism was significantly associated with increased risk of normal tissue injury after radiotherapy in breast cancer patients, and XRCC1 R399Q polymorphism is a genetic marker of normal tissue injury after radiotherapy in breast cancer patients.
KeywordsXRCC1 Breast cancer Normal tissue injury Radiotherapy
We thank all the persons who give the help for the study.
Conflicts of interest
- 10.Andreassen CN, Alsner J, Overgaard M, Sorensen FB, Overgaard J. Risk of radiation-induced subcutaneous fibrosis in relation to single nucleotide polymorphisms in TGFB1, SOD2, XRCC1, XRCC3, APEX and ATM—a study based on DNA from formalin fixed paraffin embedded tissue samples. Int J Radiat Biol. 2006;82:577–86.PubMedCrossRefGoogle Scholar
- 15.Raabe A, Derda K, Reuther S, Szymczak S, Borgmann K, Hoeller U, et al. Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy. Radiat Oncol. 2012;7:65.PubMedCentralPubMedCrossRefGoogle Scholar
- 17.Terrazzino S, La Mattina P, Masini L, Caltavuturo T, Gambaro G, Canonico PL, et al. Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery. Radiother Oncol. 2012;103:199–205.PubMedCrossRefGoogle Scholar
- 22.Moullan N, Cox DG, Angele S, Romestaing P, Gerard JP, Hall J. Polymorphisms in the DNA repair gene xrcc1, breast cancer risk, and response to radiotherapy. Cancer Epidemiol Biomark Prev. 2003;12:1168–74.Google Scholar
- 23.Giotopoulos G, Symonds RP, Foweraker K, Griffin M, Peat I, Osman A, et al. The late radiotherapy normal tissue injury phenotypes of telangiectasia, fibrosis and atrophy in breast cancer patients have distinct genotype-dependent causes. Br J Cancer. 2007;96:1001–7.PubMedCentralPubMedCrossRefGoogle Scholar
- 25.Falvo E, Strigari L, Citro G, Giordano C, Arcangeli S, Soriani A, et al. Dose and polymorphic genes xrcc1, xrcc3, gst play a role in the risk of articledeveloping erythema in breast cancer patients following single shot partial breast irradiation after conservative surgery. BMC Cancer. 2011;11:291.PubMedCentralPubMedCrossRefGoogle Scholar