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Published on: February 12, 2017
Correlation of MSH3 polymorphisms with response and survival in advanced non-small cell lung cancer patients treated
1Key Laboratory on Diagnosis and Treatment Technology for Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute).
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.
Insights
Genetic variations in the MSH3 gene impact treatment response and survival for advanced non-small cell lung cancer (NSCLC) patients undergoing platinum-based chemotherapy. Specific MSH3 polymorphisms correlate with chemotherapy sensitivity and progression-free survival.
Area of Science:
- Oncology
- Genetics
- Pharmacogenomics
Background:
- Mismatch repair (MMR) genes are crucial for removing cisplatin-DNA adducts.
- Mutations in MMR genes can reduce sensitivity to platinum-based therapies.
- The role of MSH3 gene polymorphisms in non-small cell lung cancer (NSCLC) response to chemotherapy requires further investigation.
Purpose of the Study:
- To investigate the association between MSH3 gene polymorphisms and the response to platinum-based chemotherapy in advanced NSCLC patients.
- To evaluate the impact of MSH3 polymorphisms on progression-free survival (PFS) in this patient cohort.
Main Methods:
- Genotyping of MSH3 polymorphisms (rs26279, rs1650697, rs1105524) was performed on peripheral blood samples from 180 advanced NSCLC patients.
- Patients received first-line platinum-based chemotherapy.
- Statistical analyses were used to determine associations between genotypes, chemotherapy response, and survival outcomes.
Main Results:
- A significant association was found between the MSH3 rs26279 (Ala1054Thr) polymorphism and sensitivity to platinum-based chemotherapy (P = 0.014).
- The MSH3 rs1105524 polymorphism was significantly correlated with PFS. Patients with G/A and A/A genotypes had shorter median PFS (14.27 months) compared to G/G genotype (26.37 months) (P = 0.04).
Conclusions:
- Single nucleotide polymorphisms (SNPs) in the MSH3 gene influence the chemotherapy response and prognosis of advanced NSCLC patients treated with platinum-based agents.
- MSH3 polymorphisms may serve as predictive biomarkers for platinum-based chemotherapy outcomes in NSCLC.
