Genetic variations in cell-cycle pathway and the risk of oral premalignant lesions.
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.
Ye
Yuanqing
Y
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Lippman
Scott M
SM
Lee
J Jack
JJ
Chen
Meng
M
Frazier
Marsha L
ML
Spitz
Margaret R
MR
Wu
Xifeng
X
D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D012907:Smoking
C530104:CCND1 protein, human; D018797:Cell Cycle Proteins; D019938:Cyclin D1