Association between the V109G polymorphism of the p27 gene and the risk and progression of oral squamous cell carcinoma

Purpose: Abnormalities in p27 may alter cell cycle delay required for DNA repair after exposure to carcinogens. A coding exon 1 polymorphism at codon 109 (T-->G) in p27 was identified and thought to have an effect on the functions of its protein. We hypothesized that this p27 T109G polymorphism is associated with squamous cell carcinoma of the head and neck (SCCHN) risk. Experimental Design: We tested this hypothesis in a hospital-based case-control study of 713 patients newly diagnosed with SCCHN and 1224 cancer-free controls frequency matched to the cases by age (+/- 5 years), sex, and smoking status. All subjects were non-Hispanic whites. We genotyped for this p27 variant using genomic DNA from each subject. Results: Compared with the p27 109VV variant, the p27 109GG variant was associated with a nonsignificantly increased risk of SCCHN [crude odds ratio (OR) = 1.29; 95% confidence interval (CI) = 0.88-1.90; adjusted OR = 1.20; 95% CI = 0.81-1.77], but the risk was statistically significant among men (adjusted OR = 1.55, 95% CI = 1.00-2.42), current alcohol users (adjusted OR = 1.68, 95 % CI = 1.01-2.82), and patients with oral cavity cancer (adjusted OR = 1.77, 95 % CI = 1.03-3.04). The p27 109GG variant was also associated with oral tumor overall stage, suggesting that it may play a role in tumor progression. Conclusions: Our findings suggest that the p27 109GG variant genotype may not play a major role in the etiology of SCCHN but may be associated with an increased risk in at-risk subgroups or subsets of SCCHN, particularly oral cavity cancer and possibly tumor progression. Larger studies with oral squamous cell carcinoma are needed to verify these findings.