p73 G4C14-to-A4T14 polymorphism and risk of lung cancer.
Genetic variants in genes controlling cellular processes such as cell cycle, DNA repair, and apoptosis may modulate lung cancer risk. p73 has some p53-like activity and plays an important role in modulating these processes. The noncoding region of exon 2 of the p73 gene has two polymorphisms that are in complete linkage disequilibrium with one another, which may alter translation efficiency of the p73 protein. To test the hypothesis that this p73 polymorphism plays a role in the etiology of lung cancer, we conducted a hospital-based case-control study of 1054 patients newly diagnosed with lung cancer and 1139 cancer-free controls and evaluated the association between the p73 variant AT allele and risk of lung cancer. Cancer-free controls were frequency matched to the cases by age (+/-5 years), sex, and smoking status, and all subjects were non-Hispanic whites. The variant AT allele and genotypes were more common among the cases than among the controls (P = 0.0007 and P < 0.001, respectively). Compared with the GC/GC genotype, the variant GC/AT and AT/AT genotypes were associated with a statistically significantly increased risk for lung cancer [adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI), 1.10-1.59 and OR = 1.54, 95% CI, 1.05-2.26, respectively] in an allele dose-effect relationship (trend test: P < 0.001). The risk associated with the AT allele (GC/AT+AT/AT) was more pronounced in younger (</=50 years) individuals (OR = 1.53, 95% CI, 1.00-2.37), men (OR = 1.61, 95% CI, 1.26-2.06), light smokers (OR = 1.58, 95% CI, 1.17-2.14), and squamous cell lung carcinoma (OR = 1.79, 95% CI, 1.32-2.42). These results suggest that this p73 polymorphism may be a marker for susceptibility to lung cancer.
Li
Guojun
G
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Wang
Li-E
LE
Chamberlain
Robert M
RM
Amos
Christopher I
CI
Spitz
Margaret R
MR
Wei
Qingyi
Q
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins