CASP3 Polymorphisms and Risk of Squamous Cell Carcinoma of the Head and Neck

• Published in: Clinical cancer research Vol. 14; no. 19; pp. 6343 - 6349
• Main Authors: Chen, Kexin, Zhao, Hui, Hu, Zhibin, Wang, Li-E, Zhang, Wei, Sturgis, Erich M., Wei, Qingyi
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2008
• Subjects: 5' Untranslated Regions; Aged; Antineoplastic agents; Apoptosis; Biological and medical sciences; Carcinoma, Squamous Cell - genetics; Case-Control Studies; Case-control study; Caspase 3 - genetics; Female; Genetic susceptibility; Haplotypes; Head and Neck Neoplasms - genetics; Humans; Male; Medical sciences; Middle Aged; Molecular epidemiology; Odds Ratio; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Polymorphism; Polymorphism, Genetic; Regression Analysis; Risk; Tumors; Genetic variability; Risk factor; ENT disease; Head and neck cancer; Head and neck squamous cell carcinoma; Genotype; Malignant tumor; Cancer; Polymorphism
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-1198

Purpose: Caspase-3 plays a central role in executing cell apoptosis and thus in carcinogenesis, but little is known about the role of CASP3 variants in susceptibility to SCCHN. Experimental Design: Genotype and haplotypes of the first intron (rs4647601:G>T and rs4647602:C>A) and 5′-untranslated region (UTR; rs4647603:G>A) of CASP3 (NT_022792.17) were determined for 930 SCCHN patients and 993 cancer-free controls in a U.S. non-Hispanic white population. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated in multivariate logistic regression analysis. Results: We found that the CASP3 rs4647601:TT variant genotype was associated with an increased risk of SCCHN (adjusted OR, 1.32; 95% CI, 1.00-1.73) compared with the GG genotype. This risk was more evident in the subgroups of younger (≤56 years) subjects, males, and never smokers with a significant trend for increased risk with increased number of variant T allele ( P < 0.05 for all). However, these risks were not found for other two SNPs. Furthermore, individuals with two copies of haplotypes TCG or GCA were found to have a significant increased risk of SCCHN (OR, 1.31; 95% CI, 1.07-1.61) compared with the other haplotypes, and this risk was more evident in less advanced diseases (OR, 1.45; 95% CI, 1.11-1.89) than in the advanced diseases (OR, 1.22; 95% CI, 0.96-1.54). Conclusions: These results suggested that genetic variation in CASP3 may contribute to SCCHN risk. Larger studies are needed to confirm our findings.