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CASP7 variants modify susceptibility to cervical cancer in Chinese women.

Shi TY, He J, Wang MY, Zhu ML, Yu KD, Shao ZM, Sun MH, Wu X, Cheng X, Wei Q - Sci Rep (2015)

Bottom Line: The genotype-phenotype correlation was performed by a generalized linear regression model.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.

View Article: PubMed Central - PubMed

Affiliation: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Obstetrics and Gynecology, Zhongshan Hospital Fudan University, Shanghai 200032, China.

ABSTRACT
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.

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Related in: MedlinePlus

The relative expression levels of CASP7 mRNA by different genotypesin 270 HapMap subjects.(A) rs4353229, (B) rs10787498, (C) rs12247479, (D) rs1127687,as well as the joint effects of (E) rs12247479 with rs4353229, (F) rs10787498with rs4353229, (G) rs10787498 with rs12247479, (H) rs1127687 with rs4353229,(I) rs1127687 with rs12247479 and (J) rs1127687 with rs10787498 are evaluatedby generalized linear models and Student's t tests.
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f2: The relative expression levels of CASP7 mRNA by different genotypesin 270 HapMap subjects.(A) rs4353229, (B) rs10787498, (C) rs12247479, (D) rs1127687,as well as the joint effects of (E) rs12247479 with rs4353229, (F) rs10787498with rs4353229, (G) rs10787498 with rs12247479, (H) rs1127687 with rs4353229,(I) rs1127687 with rs12247479 and (J) rs1127687 with rs10787498 are evaluatedby generalized linear models and Student's t tests.

Mentions: In 270 HapMap individuals whose mRNA expression data were available, althoughthere was no correlation of CASP7 mRNA expression levels with the riskloci, we did observe a board-line significant correlation of CASP7mRNA expression levels with the joint effect of rs10787498 and rs12247479 [generalizedlinear model (GLM), P = 0.056; Figure 2G].Moreover, CASP7 mRNA expression levels showed an increased trend forrs10787498TT-rs12247479GG carriers and a decreased trend for rs1127687AG/AA-rs10787498GT/GGcarriers (Student's t test, P = 0.018 and 0.064, respectively; Figure 2G, 2J).


CASP7 variants modify susceptibility to cervical cancer in Chinese women.

Shi TY, He J, Wang MY, Zhu ML, Yu KD, Shao ZM, Sun MH, Wu X, Cheng X, Wei Q - Sci Rep (2015)

The relative expression levels of CASP7 mRNA by different genotypesin 270 HapMap subjects.(A) rs4353229, (B) rs10787498, (C) rs12247479, (D) rs1127687,as well as the joint effects of (E) rs12247479 with rs4353229, (F) rs10787498with rs4353229, (G) rs10787498 with rs12247479, (H) rs1127687 with rs4353229,(I) rs1127687 with rs12247479 and (J) rs1127687 with rs10787498 are evaluatedby generalized linear models and Student's t tests.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363885&req=5

f2: The relative expression levels of CASP7 mRNA by different genotypesin 270 HapMap subjects.(A) rs4353229, (B) rs10787498, (C) rs12247479, (D) rs1127687,as well as the joint effects of (E) rs12247479 with rs4353229, (F) rs10787498with rs4353229, (G) rs10787498 with rs12247479, (H) rs1127687 with rs4353229,(I) rs1127687 with rs12247479 and (J) rs1127687 with rs10787498 are evaluatedby generalized linear models and Student's t tests.
Mentions: In 270 HapMap individuals whose mRNA expression data were available, althoughthere was no correlation of CASP7 mRNA expression levels with the riskloci, we did observe a board-line significant correlation of CASP7mRNA expression levels with the joint effect of rs10787498 and rs12247479 [generalizedlinear model (GLM), P = 0.056; Figure 2G].Moreover, CASP7 mRNA expression levels showed an increased trend forrs10787498TT-rs12247479GG carriers and a decreased trend for rs1127687AG/AA-rs10787498GT/GGcarriers (Student's t test, P = 0.018 and 0.064, respectively; Figure 2G, 2J).

Bottom Line: The genotype-phenotype correlation was performed by a generalized linear regression model.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.

View Article: PubMed Central - PubMed

Affiliation: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Department of Obstetrics and Gynecology, Zhongshan Hospital Fudan University, Shanghai 200032, China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus