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

Xiao Song; Shiming Wang; Xuan Hong; Xiaoying Li; Xueying Zhao; Cong Huai; Hongyan Chen; Zhiqiang Gao; Ji Qian; Jiucun Wang; Baohui Han; Chunxue Bai; Qiang Li; Junjie Wu; Daru Lu

doi:10.1038/s41598-017-08257-7

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

Sci Rep. 2017 Sep 18;7(1):11785. doi: 10.1038/s41598-017-08257-7.

Authors

Xiao Song^{1

2}, Shiming Wang¹, Xuan Hong³, Xiaoying Li¹, Xueying Zhao¹, Cong Huai¹, Hongyan Chen¹, Zhiqiang Gao⁴, Ji Qian¹, Jiucun Wang¹, Baohui Han⁴, Chunxue Bai⁵, Qiang Li⁶, Junjie Wu¹, Daru Lu⁷

Affiliations

¹ State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
² Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
³ Department of Thoracic surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
⁴ Department of Respiratory Disease, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
⁵ Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai, China.
⁷ State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China. drlu@fudan.edu.cn.

Abstract

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.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / mortality
Carcinoma, Squamous Cell* / drug therapy
Carcinoma, Squamous Cell* / genetics
Carcinoma, Squamous Cell* / mortality
Cisplatin / administration & dosage*
DNA Repair / genetics*
Female
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / mortality
Male
Middle Aged
Neoplasm Proteins / genetics*
Polymorphism, Single Nucleotide*

Substances

Neoplasm Proteins
Cisplatin