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Effects of CYP3A5 genetic polymorphism and smoking on the prognosis of non-small-cell lung cancer

Authors Jiang L, Zhu Z, He C

Received 10 August 2015

Accepted for publication 6 November 2015

Published 14 March 2016 Volume 2016:9 Pages 1461—1469

DOI https://doi.org/10.2147/OTT.S94144

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Xie Maohua

Peer reviewer comments 3

Editor who approved publication: Dr Jianmin Xu

Li-Peng Jiang,1 Zhi-Tu Zhu,2 Chun-Yan He3

1Department of Radiation Oncology, 2Department of Oncology, First Affiliated Hospital of Liaoning Medical University, 3Department of Prosthodontics, Second Affiliated Hospital of Liaoning Medical University, Jinzhou, People’s Republic of China

Objective: We aimed to explore the impacts of the rs776746 polymorphism in the CYP3A5 gene and smoking on the prognosis of non-small-cell lung cancer (NSCLC).
Materials and methods: Our study enrolled 104 early NSCLC patients undergoing surgery and 107 advanced NSCLC patients undergoing chemotherapy, hospitalized between December 2009 and December 2012 at the First Affiliated Hospital of Liaoning Medical University. All subjects with complete follow-up data were pathologically diagnosed. The rs776746 polymorphism and different genotypes (*1/*1, *1/*3, and *3/*3) were identified by polymerase chain-reaction restriction fragment-length polymorphism.
Results: Clinical response to chemotherapy in NSCLC patients with *1/*1 + *1/*3 genotypes were significantly worse than in those with the *3/*3 genotype (17.78% vs 56.45%, P<0.001), and after Bonferroni adjustment, the differences still showed significance (Pc<0.01). The mortality risk of NSCLC patients undergoing chemotherapy with the *3/*3 genotype was 0.617 times those with *1/*1 + *1/*3 genotypes (relative risk [RR] 0.617, 95% confidence interval [CI] 0.402–0.948; P=0.028), while the mortality risk of smoking patients was 1.743 times greater than that of nonsmoker patients (RR 1.743, 95% CI 1.133–2.679; P=0.042). Furthermore, a 3.087-fold mortality risk was found in NSCLC patients undergoing surgery with the *3/*3 genotype compared with those with *1/*1 + *1/*3 genotypes (RR 3.087, 95% CI 1.197–7.961; P=0.020). In NSCLC patients undergoing surgery, the mortality risk of smokers was 1.896 times greater than nonsmokers (RR 1.896, 95% CI 1.040–3.455; P=0.037).
Conclusion: Our study demonstrated that the CYP3A5 rs776746 polymorphism and smoking may influence the prognosis of NSCLC patients undergoing chemotherapy and surgery.

Keywords: cytochrome P450 3A5, non-small-cell lung cancer, smoking, polymorphism, prognosis, chemotherapy, surgery

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