title: Association between single nucleotide polymorphisms (SNPs) and toxicity of advanced non-small-cell lung cancer patients treated with chemotherapy.
abstract: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) could influence chemosensitivity. In this study, we assessed whether polymorphisms in genes of nucleotide excision repair (NER) pathway, including ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based chemotherapy in NSCLC patients. We used AllGloTM probe to assess genotyping and polymorphisms in 388 stage IIIB and IV NSCLC patients treated with platinum-based chemotherapy. MMS19L might be associated with the adverse events of chemotherapy in NSCLC, especially for all grade leucopenia (P = 0.020), all grade jaundice (P = 0.037) and all grade creatinine increasing (P = 0.013). In terms of grade 3/4 adverse events, MMS19L was related with total grade 3/4 adverse events (P = 0.024) and grade 3/4 thrombocytopenia (P = 0.035), while RRM1 was related with total grade 3/4 adverse events (P = 0.047) and grade 3/4 vomiting (P = 0.046). ERCC5 was related with more infection (P = 0.017). We found that some SNPs in NER pathway genes were correlated with toxicity treated with double chemotherapy in advanced NSCLC patients, especially for SNPs of MMS19L, RRM1 and ERCC5.
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Cancer Institute, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Gao
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.forename: Aiwu
authors.initials: A
authors.lastname: Li
authors.forename: Jianfang
authors.initials: J
authors.lastname: Xu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D010984:Platinum