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Polymorphisms in  Caspase-7  ( CASP7 ) may modulate the programmed cell death and thus contribute to cervical cancer risk. In this case-control study of 1,486 cervical cancer cases and 1,301 controls, we investigated associations between four potentially functional polymorphisms in  CASP7  and cervical cancer risk and evaluated their locus-locus interaction effects on the risk. The genotype-phenotype correlation was performed by a generalized linear regression model. We found that the rs4353229 polymorphism was associated with cervical cancer risk (under a recessive model: crude OR = 1.20, 95% CI = 1.02–1.40). Compared with the TT genotype, the rs10787498GT genotype was associated with an increased cervical cancer risk (adjusted OR = 1.19, 95% CI = 1.00–1.41). Combination analysis showed that subjects with four putative risk genotypes had a 1.54-fold increased cancer risk, compared with those who carried three or less putative risk genotypes. We also observed significant locus-locus joint effects on the risk, which may be mediated by the polymorphisms regulating  CASP7  mRNA expression. Subsequent multifactor dimensionality reduction and classification and regression tree analyses indicated that the  CASP7  genotypes might have a locus-locus interaction effect that modulated cervical cancer risk. Out data suggest that  CASP7  polymorphisms may interact to modify cervical cancer risk by a possible mechanism of regulating  CASP7  mRNA expression.

CASP7 variants modify susceptibility to cervical cancer in Chinesewomen