Association of XPC polymorphisms with susceptibility and clinical outcome to chemotherapy in breast cancer patients

The aim of the current study was to evaluate the relation between xeroderma pigmentosum complementation group C ( XPC ) polymorphisms and susceptibility to breast cancer ( BC ), the development and progression of disease, and response to different individualized drug treatments. We investigated two polymorphisms in XPC A la499 V al and L ys939 G ln using PCR ‐ RFLP assays including 618 cases and 622 controls. The frequency of the TT genotype of A la499 V al (adjusted odds ratio = 1.575; 95% confidence interval, 1.104–2.245; P  = 0.012) and the AC genotype of L ys939 G ln (adjusted odds ratio = 1.330; 95% confidence interval, 1.045–1.694; P  = 0.020) were found to significantly increase the risk of developing BC . The CT + TT genotypes of A la499 V al were associated with estrogen receptor positive, and H er‐2 and p53 negative status, and the AC + CC genotypes of L ys939 G ln were associated with BRCA 1 negative status. Moreover, a significantly increased chance of treatment with neoadjuvant anthracycline‐based chemotherapy response was found in women carrying TT genotype of A la499 V al, or CC and AC genotypes of L ys939 G ln. In addition, a significantly longer overall survival after chemotherapy was observed in patients who had XPC L ys939 G ln AC + CC genotypes with estrogen receptor positive (log–rank test, P  = 0.086) and p53 negative (log–rank test, P  = 0.020). The current data suggested that XPC A la499 V al and L ys939 G ln polymorphisms may contribute to the identification of patients with increased risk for BC . Moreover, the polymorphisms were associated with the prognosis of BC patients. ( Cancer Sci 2012; 103: 1207–1214)