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18 February 2019 : Laboratory Research  

Functional Genetic Single-Nucleotide Polymorphisms (SNPs) in Cyclin-Dependent Kinase Inhibitor 2A/B (CDKN2A/B) Locus Are Associated with Risk and Prognosis of Osteosarcoma in Chinese Populations

Huahui Zhang1ABCDEFG*, Jian-S. Mao2BCD, Wei-F. Hu3CD

DOI: 10.12659/MSM.915001

Med Sci Monit 2019; 25:1307-1313

Abstract

BACKGROUND: Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) encodes several tumor suppressor proteins. Aberrant genetic alterations in CDKN2A/B were found in some malignancies, which were believed to be associated with tumor originating and progression. We hypothesized that CDKN2A/B genetic polymorphisms might be associated with the risk of poorer prognosis of osteosarcoma in Chinese populations.

MATERIAL AND METHODS: We included 184 validated osteosarcoma cases and 185 cancer-free healthy controls in the study. Five single-nucleotide polymorphisms of CDKN2A/B (rs1063192, rs3218009, rs3217986, rs3217992, and rs3731257) were genotyped and underwent bioinformatic analysis. DNA from osteosarcoma individuals was isolated from frozen peripheral blood and DNA from healthy controls was extracted from fresh prepared peripheral blood.

RESULTS: An allele of the SNP rs3217992 is predictive for susceptibility to osteosarcoma, and it is associated with poorer prognosis of osteosarcoma. The GA and AA genotypes of rs3217992 are related to elevated risk of osteosarcoma. In addition, the GA and AA genotypes of rs3217992 in CDKN2A might indicate higher stage and increased risk of lung metastasis of osteosarcoma, resulting in worse prognosis.

CONCLUSIONS: Functional genetic polymorphisms in CDKN2A/B predict the susceptibility and outcome of osteosarcoma in Chinese individuals.

Keywords: Genes, p16, Osteosarcoma, Polymorphism, Genetic, Adolescent, Alleles, Asians, Case-Control Studies, Child, China, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p16, Gene Frequency, Genetic Predisposition to Disease, Genotype, Male, Polymorphism, Single Nucleotide, Prognosis, Risk Factors, Tumor Suppressor Proteins, young adult

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750