XRCC1 R399Q polymorphism and risk of normal tissue injury after radiotherapy in breast cancer patients

Abstract

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.

Predictive value of single nucleotide polymorphisms in <em>XRCC1</em> for radiation-induced normal tissue toxicity

“…So far, four meta-analyses have been published on XRCC1 polymorphism and the risk of normal tissue injury after RT, three of which were performed only in breast cancer and one in prostate cancer patients; besides, only one to three polymorphisms have been analyzed in each paper. 13 , 46 , 64 , 65 A positive association between rs25487 Arg399Gln polymorphism and acute side effect in breast cancer patients, 64 , 65 and a negative association between rs25489 Arg280His variant and late side effect in breast cancer and prostate cancer patients 46 , 65 have been reported in these meta-analyses.…”

Predictive SNPs for radiation-induced damage in lung cancer patients with radiotherapy: a potential strategy to individualize treatment

“…Given their significance in interindividual differences, research through the study of SNPs into adverse responses of normal tissues is rapidly increasing. These results indicate the significant differential expression and functional role of SNPs in the prediction of radiation-induced toxicities, suggesting that SNPs could potentially serve as their biologic markers (23–24–25–26). However, the search for SNPs as predictive biomarkers has just begun, with no definitive conclusion yet reached as to which patients might benefit from such a strategy.…”

Polymorphisms in X-Ray Repair Cross-Complementing Group 1 Gene: Haplotypes, Breast Cancer Risk and Individual Radiosensitivity

“…Nevertheless, a predictive value of XRCC1-399 SNP was found in studies with mixed treatment regimens when studies on only late toxicity were excluded. Another meta-analysis including 14 case-control studies, 13 of which were performed in European countries, evaluated the association between XRCC1-399 SNP and the risk of normal tissue injury after radiotherapy in BC patients [29]. This meta-analysis suggests that XRCC1-399 SNP was significantly associated with increased risk of adverse normal tissue reactions after radiation therapy.…”