Association ofXRCC1Variants with Acute Skin Reaction After Radiotherapy in Breast Cancer Patients

Abstract

After irradiation results in cytotoxic effects by DNA damage, base excision repair (BER) pathway is involved in the repair of single-strand breaks and nonhomologous end joining and homologous repair of double-strand breaks caused by radiotherapy. Alterations in the function of BER DNA repair genes may affect DNA repair proficiency and influence the response of patients with cancer to radiotherapy. The association of single nucleotide polymorphisms of BER DNA repair X-ray repair cross-complementing group 1 protein (XRCC1) and risk of radiotherapy-induced ≥grade 2 acute skin reaction in patients with breast cancer was examined. It was found that the risk of ≥grade 2 acute skin toxicity after radiotherapy could be increased by 2.86-fold in patients carrying the XRCC1 -77TC and CC genotypes (p = 0.016). However, the other three coding XRCC1 variants did not influence the risk of ≥grade 2 acute skin toxicity for patients with breast cancer after radiotherapy. Our results suggested that the XRCC1 polymorphism is associated with increased risk of radiation-induced acute skin reaction in a Chinese population.

Predictive Value of Xrcc1 Gene Polymorphisms for Side Effects in Patients undergoing Whole Breast Radiotherapy: a Meta-analysis

“…After application of critical search strategies and exclusion criteria, 11 follow-up studies (Moullan et al, 2003;Chang-Claude et al, 2005;Brem et al, 2006;Giotopoulos et al, 2007;Chang-Claude et al, 2009;Zhou et al, 2010;Zschenker et al, 2010;Mangoni et al, 2011;Falvo et al, 2012;Raabe et al, 2012;Terrazzino et al, 2012) comprising 2199 cases were eligible for the present analysis. The baseline characteristics of the included studies are shown in Table 1.…”

“…The baseline characteristics of the included studies are shown in Table 1. Ten of these studies included mainly Caucasian patients and one study included only Chinese patients (Zhou et al, 2010). All of them were published in English-language journals.…”

“…A total of 6 studies used PCR-RFLP genotyping methods. Genotypes were verified by sequencing of all samples in one study (Zschenker et al, 2010), partially verified in 20% of samples in one study (Zhou et al, 2010), and not verified in the rest of the studies (Brem et al, 2006;Giotopoulos et al, 2007;Zhou et al, 2010;Raabe et al, 2012). All studies used samples of peripheral blood.…”

“…Data concerning the predictive value of the XRCC1 Arg399Gln allele with respect to the risk of radiationinduced toxicity in breast cancer patients were available in 10 trials comprising 1929 individuals (Moullan et al, 2003;Chang-Claude et al, 2005;Giotopoulos et al, 2007;Chang-Claude et al, 2009;Zschenker et al, 2010;Zhou et al, 2010;Mangoni et al, 2011;Terrazzino et al, 2012;Falvo et al, 2012;Raabe et al, 2012). No significant association between the 399Gln allele and radiationinduced toxicity was detected in the overall analysis (Table 3).…”

“…Another study that did not differentiate between early and late adverse reactions to radiotherapy reported an elevated risk in women carrying variant alleles of the Arg194Trp and the Arg399Gln polymorphisms (Moullan et al, 2003). Zhou et al (2010) reported that the risk of ≥grade 2 acute skin toxicity after radiotherapy could be increased by 2.86-fold in patients carrying the XRCC1-77TC and CC genotypes. Two published studies have addressed the impact of the XRCC1 position 194, 280, and 399 polymorphisms on the risk of late adverse reactions after radiotherapy for prostate cancer.…”