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Keywords:

  • cell-cycle pathway;
  • single-nucleotide polymorphisms;
  • oral premalignant lesion;
  • classification and regression tree analysis

Abstract

BACKGROUND.

Cell-cycle checkpoint controls regulate cell-cycle progression and proliferation. Alterations in cell-cycle control mechanisms are linked to tumorigenesis.

METHODS.

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.

RESULTS.

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.

CONCLUSIONS.

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.