Relationship of ERCC1,XPD,and BRCA1 polymorphisms with efficacy of platinum-based chemotherapy for patients with advanced non-small cell lung cancer

Abstract

Objective To investigate the relationship of excision repair cross-complementing 1(ERCC1),xeroderma pigmentosum group D(XPD),and breast cancer susceptibility gene 1(BRCA1) polymorphisms with the efficacy of platinum-based chemotherapy for treatment of the patients with advanced non-small cell lung cancer.Methods A total of 124 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy,and their clinical responses were evaluated.ERCC1 Asn118Asn(rs11615),XPD Lys751Gln(rs13181) and BRCA1 Ser1613Gly(rs1799966) of the patients were genotyped using the TaqMan method.The association of ERCC1 Asn118Asn,XPD Lys751Gln and BRCA1 Ser1613Gly polymorphisms with the patient responses was analyzed using unconditional logistic regression model.Results It was found that the BRCA1 Ser1613Gly polymorphism was significantly correlated with clinical benefit(P=0.014).Patients carrying Gly allele had better clinical benefit than patients with wildtype allele(P=0.006).No significant association was found between ERCC1 and XPD polymorphisms with clinical benefit.Furthermore,we found that the three SNPs in NER(nucleotide excision repair) could work together.More variant alleles(ERCC1 T,XPD Gln and BRCA1 Gly) was associated with better clinical benefit(P=0.036).Conclusion The BRCA1 Ser1613Gly polymorphism of NER is associated with the clinical benefit of NSCLC patients receiving platinum-based chemotherapy.Analysis of SNPs of more genes may help to guide drug choosing for chemotherapy.