CASP8 (rs3834129) and CASP3 (rs4647601) polymorphisms in oropharynx cancer risk, tumor cell differentiation, and prognosis in a cohort of the Brazilian population

The objective of this research was to assess the association of genetic polymorphisms related to intrinsic apoptosis pathway CASP8 rs3834129 and CASP3 rs4647601 with the risk, clinical and pathological aspects, and survival of oropharynx squamous cell carcinoma (OPSCC) patients that received cisplat...

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Published in:	Molecular biology reports Vol. 46; no. 6; pp. 6557 - 6563
Main Authors:	Tortorelli, Gabriela Arielo, Torricelli, Caroline, Carron, Juliana, Costa, Ericka Francislaine Dias, Lopes-Aguiar, Leisa, Carvalho, Bruna Fernandes, Rinck-Junior, José Augusto, Mariano, Fernanda Viviane, Altemani, Albina Messias Almeida Milani, Lima, Carmen Silvia Passos, Lourenço, Gustavo Jacob
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer Netherlands 01-12-2019 Springer Nature B.V
Subjects:	Adult Aged Aged, 80 and over Alleles Animal Anatomy Animal Biochemistry Apoptosis Biomedical and Life Sciences Brazil Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - mortality Case-Control Studies Caspase 3 - genetics Caspase 8 - genetics Cell Differentiation Cell survival Cisplatin Disease Progression Down-Regulation Female Gene Expression Regulation, Neoplastic Genetic diversity Genetic Predisposition to Disease Genotype Genotype & phenotype Histology Humans Life Sciences Male Medical prognosis Middle Aged Morphology Oropharyngeal Neoplasms - genetics Oropharyngeal Neoplasms - mortality Oropharynx Polymerase chain reaction Polymorphism, Single Nucleotide Prognosis Radiation therapy Short Communication Squamous cell carcinoma Survival Analysis Throat cancer Tumors Brazil CASP8 Prognosis CASP3 Tumor cell differentiation Oropharynx cancer Risk Apoptosis Polymorphism
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Summary:	The objective of this research was to assess the association of genetic polymorphisms related to intrinsic apoptosis pathway CASP8 rs3834129 and CASP3 rs4647601 with the risk, clinical and pathological aspects, and survival of oropharynx squamous cell carcinoma (OPSCC) patients that received cisplatin and radiotherapy. The genotypes were identified in 198 patients with OPSCC and 200 controls using polymerase chain reaction methods. Chi square or Fisher’s exact test and logistic regression were applied for the detection of differences between groups. Patients’ genotypes were statistically evaluated considering the event-free survival and overall analysis using Kaplan–Meier estimate and Cox regression. CASP3 rs4647601 GG genotype (44.4% vs. 30.0%, p = 0.03) and G allele (63.9% vs. 55.5%, p = 0.04) were more common in patients with OPSCC than in controls. Carriers of GG genotype and G allele were under 1.78-fold and 1.40-fold increased risk of OPSCC than others, respectively. The frequency of CASP8 rs3834129 DD genotype was higher in patients with OPSCC with poorly differentiated or undifferentiated tumors when compared to others (34.5% vs. 16.1%, p = 0.02). No influence of CASP8 and CASP3 polymorphisms on OPSCC patients’ survival was seen in this study. Our results indicate that inherited genetic variants in the intrinsic apoptosis pathway related to CASP3 rs4647601 and CASP8 rs3834129 polymorphisms may be an important determinant of OPSCC risk and tumor cell differentiation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0301-4851 1573-4978
DOI:	10.1007/s11033-019-05107-9