The Role of Caspase Genes Polymorphisms in Genetic Susceptibility to Philadelphia-Negative Myeloproliferative Neoplasms in a Portuguese Population

• Published in: Pathology oncology research Vol. 25; no. 3; pp. 961 - 969
• Main Authors: Azevedo, Ana P., Silva, Susana N., Reichert, Alice, Lima, Fernando, Júnior, Esmeraldina, Rueff, José
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-07-2019; Springer Nature B.V
• Subjects: Adult; Alleles; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Caspase; Caspases - genetics; Female; Genetic Predisposition to Disease - genetics; Genotype; Humans; Immunology; Janus kinase 2; Male; Middle Aged; Myeloproliferative Disorders - genetics; Oncology; Original Article; Pathology; Polymorphism, Single Nucleotide - genetics; Portugal; Single-nucleotide polymorphism; Thrombocythemia, Essential - genetics; Tumors; Portugal; Caspase genes polymorphisms; Genetic susceptibility; Janus kinase 2; Philadelphia-negative myeloproliferative neoplasms
• ISSN: 1219-4956; 1532-2807
• DOI: 10.1007/s12253-018-0411-y

Our main aim was to evaluate the role of caspases’ genes SNPs in Philadelphia-chromosome negative chronic myeloproliferative neoplasms (PN-MPNs) susceptibility. A case-control study in 133 Caucasian Portuguese PN-MPNs patients and 281 matched controls was carried out, studying SNPs in apoptosis related caspases: rs1045485 and rs1035142 (
CASP8
), rs1052576, rs2308950, rs1132312 and rs1052571 (
CASP9
), rs2227309 and rs2227310 (
CASP7
) and rs13006529 (
CASP10
). After stratification by pathology diagnosis for essential thrombocythemia (ET), female gender or
JAK2
positive, there is a significant increased risk for those carrying at least one variant allele for
CASP9
(C653T) polymorphism (OR 2.300 CI 95% [1.180–4.484],
P
 = 0.014). However, when considered individually, none of the studied caspases polymorphisms was associated with PN-MPNs risk. Our results do not reveal a significant involvement of caspase genes polymorphisms on the individual susceptibility towards PN-MPNs as a whole. However, for essential thrombocythemia (ET), female gender or
JAK2
positive, there is a significant increased risk to those carrying at least one variant allele for
CASP9
. Although larger studies are required to confirm these results and to provide conclusive evidence of association between these and other caspases variants and PN-MPNs susceptibility, these new data may contribute to a best knowledge of the pathophysiology of these disorders and, in the future, to a more rational and efficient choice of therapeutic strategies to be adopted in PN-MPNs treatment.