Association between XPD 312 single nucleotide polymorphism (SNP) and clinical outcome in stage IIIA-B non-small-cell lung cancer (NSCLC) patients (P) < 59 years (Y) treated with chemotherapy followed by surgery

Background: SNPs in DNA repair genes can be associated with increased risk of lung cancer and may affect response to cytotoxic therapy. We investigated SNPs in XPD codons 751 and 312 and in RRM1 -37 in 109 stage IIIA (N2) and IIIB NSCLC patients treated with neoadjuvant chemotherapy and correlated results with event-free (EFS) and median (MS) survival. Methods: Patients eligible for surgery received cisplatin day (d) 1, gemcitabine d 1,8, docetaxel d 1,8,15, every 3 weeks for 3 cycles, followed by thoracotomy. DNA was extracted from baseline peripheral lymphocytes and genotyping was performed by Taqman. Results: Median age, 60 years (y) (range 31-77); 92 males (84%); 45 squamous cell (41%). 4 p (3.9%) attained complete response; 55 (53.9%) partial response. 75 p underwent surgery (62 complete, 13 incomplete resection); remaining 34 p were unresectable. Median follow-up was 15.7 months (m) (range 0.5-74). In the univariate analysis of survival, age <59 y (P=0.03), resection (P<0.001) and XPD312 AspAsp (P=0.05) emerged as predictive markers of longer survival. For all 109 p, regardless of resection, those with XPD312 AspAsp had longer EFS and MS than p with Asn variants (EFS: 13.98 m versus 7.34 m; p=0.03; MS: 32.14 m versus 12.04; p=0.05). In addition, for 51 p <59 y, EFS was longer for 24 p with XPD312 AspAsp (36.4 m) than for 27 p with Asn variants (9.8 m) (P=0.009); MS in this group of younger p was 45.4 m for AspAsp vs 15.8 m for Asn (P=0.04). No other significant correlation between SNPs and survival was observed. Conclusions: Interaction between XRCC1, age and risk of lung cancer has previously been described. XPD312 AspAsp predicts longer survival, regardless of resection, in stage IIIA (N2) and IIIB NSCLC p<59 treated with neoadjuvant chemotherapy.