title: Correlation of MSH3 polymorphisms with response and survival in advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy.
abstract: Mismatch repair (MMR) genes, as well as the nucleotide excision repair genes, play an important role in removing cisplatin-DNA adducts, and the mutation of MMR genes in tumors can lead to a decreased response to platinum-based therapies. We examined MutS homolog 3 (MSH3), a mismatch repair gene, and whether polymorphisms of MSH3 were associated with response and survival in advanced non-small cell lung cancer (NCSLC) patients who were treated with platinum-based chemotherapy. The peripheral blood of 180 advanced NCSLC patients who were treated with first-line platinum-based chemotherapy was collected to determine the patients' genotypes of MSH3. The three genotypes of the MSH3 polymorphisms rs26279, rs1650697 and rs1105524 were investigated. A statistically significant association was observed between the polymorphism rs26279 (Ala1054Thr) and sensitivity to platinum-based chemotherapy (P = 0.014). A significant correlation was found between rs1105524 and progression-free survival (PFS), with the G/A and A/A genotypes (median survival time: 14.27 months; 95%CI = 9.80-18.75) suffering shorter survival than patients with the G/G genotype (median survival time: 26.37 months; 95%CI = 15.03-37.71) (P = 0.04). Our results showed that single nucleotide polymorphisms in MSH3 had an impact on the chemotherapy response and prognosis of advanced NCSLC patients who were treated with platinum-based chemotherapy.
authors.affiliation: Key Laboratory on Diagnosis and Treatment Technology for Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute).
authors.forename: X-L
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Key Laboratory on Diagnosis and Treatment Technology for Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute).
authors.forename: Y-L
authors.initials: YL
authors.lastname: Yao
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou City, China.
authors.forename: W-Z
authors.initials: WZ
authors.lastname: Xu
authors.affiliation: Key Laboratory on Diagnosis and Treatment Technology for Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute).
authors.forename: J-G
authors.initials: JG
authors.lastname: Feng
authors.affiliation: Key Laboratory on Diagnosis and Treatment Technology for Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute), maowm1318@163.com.
authors.forename: W-M
authors.initials: WM
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000074081:MutS Homolog 3 Protein; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D004268:DNA-Binding Proteins; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D016190:Carboplatin; D002945:Cisplatin