Association between eIF3α polymorphism and severe toxicity caused by platinum-based chemotherapy in non-small cell lung cancer patients
Article first published online: 10 JAN 2013
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 75, Issue 2, pages 522–534, February 2013
How to Cite
Xu, X., Han, L., Duan, L., Zhao, Y., Yang, H., Zhou, B., Ma, R., Yuan, R., Zhou, H. and Liu, Z. (2013), Association between eIF3α polymorphism and severe toxicity caused by platinum-based chemotherapy in non-small cell lung cancer patients. British Journal of Clinical Pharmacology, 75: 522–534. doi: 10.1111/j.1365-2125.2012.04379.x
- Issue published online: 10 JAN 2013
- Article first published online: 10 JAN 2013
- Accepted manuscript online: 13 JUL 2012 07:35AM EST
- Manuscript Accepted: 3 JUL 2012
- Manuscript Received: 19 OCT 2011
- National High-Tech R&D Program of China. Grant Number: 2012AA02A517
- National Natural Science Foundation of China. Grant Number: 81173129
- Programme for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China. Grant Number: IRT0946
- Special Scientific Research Foundation of Doctor Disciplines in University of Ministry of Education of China. Grant Number: 20110162110034
- Natural Science Innovation Group Foundation of Hunan Province. Grant Number: 12JJ7006
- non-small cell lung cancer (NSCLC);
- platinum toxicity
Platinum-induced toxicity severely impedes successful chemotherapy in lung cancer patients. The nucleotide excision repair (NER) pathway is considered as one of the major factors contributing to platinum effects. Furthermore, genetic variances of the NER pathway influence platinum toxicity. eIF3α, over expressed in many malignancies, is an up-stream gene of NER and could regulate its activity. The purpose of this study was to investigate whether eIF3α polymorphism is associated with severe platinum toxicity in patients with non-small cell lung cancer (NSCLC).
Two hundred and eighty-two incident NSCLC patients, from three different institutions, were enrolled and followed up. These patients were diagnosed and histologically confirmed with non-small cell lung cancer. All patients accepted platinum based chemotherapy for at least two cycles. Twenty-two SNPs of eIF3α were detected in these patients.
eIF3α Arg803Lys C > T polymorphism was associated with cisplatin-induced toxicity in NSCLC patients (P = 0.02, OR = 0.54, 95% CI 0.32, 93). T-carrier subjects presented better tolerance to platinum nephrotoxicity, but poorer tolerance to ototoxicity.
eIF3α Arg803Lys was associated with platinum toxicity in NSCLC patients and could be considered as a predictor for pretreatment evaluation in lung cancer patients.