The authors declare no conflicts of interest.
Multi-loci analysis reveals the importance of genetic variations in sensitivity of platinum-based chemotherapy in non-small-cell lung cancer
Article first published online: 20 JUL 2012
© 2012 Wiley Periodicals, Inc.
Volume 52, Issue 12, pages 923–931, December 2013
How to Cite
Liu, L., Wu, J., Zhong, R., Wu, C., Zou, L., Yang, B., Chen, W., Zhu, B., Duan, S., Yu, D., Tan, W., Nie, S., Lin, D. and Miao, X. (2013), Multi-loci analysis reveals the importance of genetic variations in sensitivity of platinum-based chemotherapy in non-small-cell lung cancer. Mol. Carcinog., 52: 923–931. doi: 10.1002/mc.21942
Li Liu, Jing Wu, and Rong Zhong contributed equally to this work.
- Issue published online: 19 NOV 2013
- Article first published online: 20 JUL 2012
- Manuscript Accepted: 26 JUN 2012
- Manuscript Revised: 2 MAY 2012
- Manuscript Received: 19 JAN 2012
- New Century Excellent Talents in University NCET-10-0388 to X Miao
- classification and regression tree;
- multifactor dimensionality reduction;
- single nucleotide polymorphism
Polymorphisms in DNA repair and apoptotic pathways may cause variations in chemosensitivity of non-small-cell lung cancer (NSCLC) through complex gene–gene and gene–environment interactions. A total of 200 advanced NSCLC patients who received platinum-based chemotherapies were recruited. The short-term clinical outcomes were classified as chemosensitive group, including complete remission (CR) and partial remission (PR), and chemoresistant group, namely stable disease (SD) and progression disease (PD) at the end of treatment. We applied multifactor dimensionality reduction (MDR), classification and regression tree (CART) and traditional logistic regression (LR) to explore high-order gene–gene and gene–environment interactions among 11 functional single nucleotide polymorphisms (SNPs), smoking status, cancer stages and treatment regimens in the response to chemotherapy. Multi-loci analyses consistently indicated that interactions among XRCC1 Arg194Trp, XPC PAT, FAS G–1377A, and FASL T–844C were associated with sensitivity to platinum-based chemotherapy. In MDR analysis, the four-factor model yielded the highest test accuracy of 0.72 (permutation P = 0.001). In CART analysis, these four SNPs were the determinant nodes of the growth of regression tree. Patients carrying XRCC1 Arg194Arg, FAS–1377GG, and FASL–844T allele displayed completely no response to platinum, whereas patients with XRCC1 194Trp allele and XPC PAT +/+ had 68.8% response rate to platinum. In LR analysis, a significant gene–dosage effect was detected along with the increasing number of favorable genotypes of these four polymorphisms (Ptrend = 0.00002). Multi-loci analysis reveals the importance of genetic variations involved in DNA repair and apoptotic pathways in sensitivity of platinum-based chemotherapy in NSCLC. © 2012 Wiley Periodicals, Inc.