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Genetic variations in cell-cycle pathway and the risk of oral premalignant lesions
Article first published online: 29 SEP 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 9, pages 2488–2495, 1 November 2008
How to Cite
Ye, Y., Lippman, S. M., Lee, J. J., Chen, M., Frazier, M. L., Spitz, M. R. and Wu, X. (2008), Genetic variations in cell-cycle pathway and the risk of oral premalignant lesions. Cancer, 113: 2488–2495. doi: 10.1002/cncr.23854
- Issue published online: 17 OCT 2008
- Article first published online: 29 SEP 2008
- Manuscript Accepted: 9 JUN 2008
- Manuscript Revised: 30 MAY 2008
- Manuscript Received: 15 JAN 2008
- National Cancer Institute. Grant Numbers: CA106451, CA097007, CA86390
- cell-cycle pathway;
- single-nucleotide polymorphisms;
- oral premalignant lesion;
- classification and regression tree analysis
Cell-cycle checkpoint controls regulate cell-cycle progression and proliferation. Alterations in cell-cycle control mechanisms are linked to tumorigenesis.
This case-control study included 147 cases and 147 controls. The authors used a pathway-based approach to assess the association between 10 potential functional single-nucleotide polymorphisms from 7 cell-cycle control genes and the risk of oral premalignant lesions (OPLs). They also used classification and regression tree analysis to examine high-order gene-gene and gene-smoking interactions.
Compared with the homozygous wild-type GG genotype of CCND1 P241P, individuals with the AG genotype exhibited an increased risk of OPL (odds ratio, 1.58; 95% confidence interval, 0.89-2.83), and carriers of the AA genotype had a significantly increased risk of OPL (odds ratio, 2.75; 95% confidence interval, 1.33-5.71), with risk increasing significantly with the increasing number of variant alleles (P = .006). The risk of OPL increased significantly as the number of unfavorable genotypes in the pathway increased (P = .002). The final decision tree in the classification and regression tree analysis contained 5 terminal nodes. Compared with the never smokers (the lowest risk group), the odds ratios for terminal nodes 2 through 5 ranged from 1.21 to 5.40.
The results illustrated the advantage of using a pathway-based approach for analyzing gene-gene and gene-smoking interactions. Specifically, the authors showed that genetic polymorphisms in cell-cycle control pathway genes may contribute to the risk of OPL. Cancer 2008. © 2008 American Cancer Society.