CASP3 polymorphisms and risk of squamous cell carcinoma of the head and neck.
OBJECTIVE
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.


METHODS
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 (< or =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.
Chen
Kexin
K
Department of Epidemiology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
Zhao
Hui
H
Hu
Zhibin
Z
Wang
Li-E
LE
Zhang
Wei
W
Sturgis
Erich M
EM
Wei
Qingyi
Q
D020121:5' Untranslated Regions; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012306:Risk
D020121:5' Untranslated Regions; D053148:Caspase 3