Single nucleotide polymorphisms of nucleotide excision repair pathway are significantly associated with outcomes of platinum-based chemotherapy in lung cancer

Nucleotide excision repair (NER) pathway plays critical roles in repairing DNA disorders caused by platinum. To comprehensively understand the association between variants of NER and clinical outcomes of platinum-based chemotherapy, 173 SNPs in 27 genes were selected to evaluate association with toxicities and efficiency in 1004 patients with advanced non-small cell lung cancer. The results showed that consecutive significant signals were observed in XPA, RPA1, POLD1, POLD3. Further subgroup analysis showed that GTF2H4 presented consecutive significant signals in clinical benefit among adenocarcimoma. In squamous cell carcinoma, rs4150558, rs2290280, rs8067195 were significantly associated with anemia, rs3786136 was significantly related to thrombocytopenia, ERCC5 presented consecutive significant signals in response rate. In patients receiving TP regimen, significant association presented in neutropenia, thrombocytopenia and gastrointestinal toxicity. Association with anemia and neutropenia were found in GP regimen. rs4150558 showed significant association with anemia in NP regimen. In patients > 58, ERCC5 showed consecutive significant signals in gastrointestinal toxicity. Survival analysis showed SNPs in POLD2, XPA, ERCC6 and POLE were significantly associated with progression free survival, SNPs in GTF2H4, ERCC6, GTF2HA, MAT1, POLD1 were significantly associated with overall survival. This study suggests SNPs in NER pathway could be potential predictors for clinical outcomes of platinum-based chemotherapy among NSCLC.