J Cancer 2020; 11(18):5281-5288. doi:10.7150/jca.46150

Research Paper

Genetic Variants in DNA Mismatch Repair Pathway predict prognosis of Lung Cancer patients with receiving Platinum-Based Chemotherapy

Jun-Yan Liu1, Ting Zou2, Ji-Ye Yin3,4, Zhan Wang5, Ying Wang6, Zhao-Qian Liu2,3, Juan Chen7✉, Zhi-Wei Chen1✉

1. Department of Orthopaedics, The First Affiliated Hospital of the University of South China, Hengyang 421001, China.
2. National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, Hunan, P.R.China.
3. Departments of Clinical Pharmacology, Xinagya Hospital, Central South University, Changsha 410008, China.
4. Institute of Clinical Pharmacology and Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
5. Department of Medical Oncology, Lung cancer and Gastrointestinal unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, China.
6. Hunan clinical research center in gynecologic cancer, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, China.
7. Department of Pharmacy, Xinagya Hospital, Central South University, Changsha 410008, China.

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Citation:
Liu JY, Zou T, Yin JY, Wang Z, Wang Y, Liu ZQ, Chen J, Chen ZW. Genetic Variants in DNA Mismatch Repair Pathway predict prognosis of Lung Cancer patients with receiving Platinum-Based Chemotherapy. J Cancer 2020; 11(18):5281-5288. doi:10.7150/jca.46150. Available from https://www.jcancer.org/v11p5281.htm

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Abstract

Objective: To investigate the relationships between genetic variants in DNA mismatch repair pathway genes and the prognosis of platinum-based chemotherapy in lung cancer patients.

Methods: 346 lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited in this study. A total of 35 single nucleotide polymorphisms in 7 DNA mismatch repair genes were genotyped to investigate their associations with platinum-based chemotherapy prognosis.

Result: The results revealed that patients carried MSH2 rs4608577 TT genotype had a significantly shorter progression free survival than patients with GG or GT genotypes (Additive model: P=0.003, OR =0.94, 95% CI =0.33-1.57). Patients with SAPCD1 rs707937 TT genotype had a significantly longer overall survival than patients with GG or GT genotypes (Additive model: P=0.0003, OR=0.75, 95% CI =0.35-1.14). Eight SNPs and fourteen SNPs were related to progression free survival and overall survival in subgroup analyses, respectively.

Conclusion: Our findings suggest that the MSH2 rs4608577 and SAPCD1 rs707937 may be potential clinical biomarkers for predicting platinum-based chemotherapy prognosis in lung cancer patients.

Keywords: lung cancer, platinum-based chemotherapy prognosis, genetic polymorphisms, MSH2, SAPCD1, DNA mismatch repair