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

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/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.

Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

“…The results showed that the CDKN2A expression was positively related to age, ER status, PR status and molecular subtypes in breast cancer. Then, the Kaplan-Meier curves for OS also showed that reduced CDKN2A expression correlated to decreased survival time, especially in Luminal-like subtype, a nding that was in contrast to the ndings of Lee's study [15] but was consistent with the previously identi ed roles of CDKN2A in breast cancer [14,25,23]. Then Univariate and multivariate Cox analyses indicated CDKN2A expression and age were prognostic biomarkers for BC patients.…”

“…Recent studies have reported that CDKN2A functions as a tumour suppressor in different types of carcinoma, such as melanoma [10], ovarian cancer [19], lung cancer [20], atypical neuro broma [11], malignant mesothelioma [21] and bladder cancer [22]. Several studies also showed that decreased CDKN2A expression correlated to poor prognosis in osteosarcoma [23], soft tissue sarcoma [13], and oral squamous cell carcinoma [24].…”

A novel stratification framework based on anoikis-related genes for predicting the prognosis in patients with osteosarcoma

“…observed a high-frequency CDKN2A mutation in the genomic profile of patients ( 36 ). The GA and AA genotypes of rs3217992 in CDKN2A may indicate higher malignancy, higher risk of lung metastasis, and poorer prognosis ( 37 ). PHLDA2 encodes a pleckstrin homology domain-containing protein that inhibits cell proliferation by suppressing AKT activation ( 38 ).…”

The Long Non-Coding RNA ANRIL in Cancers

“…Focusing on the cancer-related pathologies, 34 SNPs were identified to be associated with higher risk of developing different types of cancer including LC, GC, BC, CC, TC, BrC, MM, PC, ATL/AML/B-ALL, melanoma/BCC, EC, ADC, HNSCC/LSCC/ESCC, PancC, OS and overall cancer risk ( Table 2 ). In addition to this trait, SNPs are also correlated, for instance, with reduced overall survival (rs1333049) in ESCC [ 165 ], with larger tumor size (rs11333048) in TC [ 166 ], with higher TMN stage (rs3217992) in OS [ 167 ], and linked to the presence of metastases (rs1063192) in TC [ 168 ] ( Table 2 ). Note that despite this clear association, most of the studies do not allow researchers to discern whether the observed associations reflect causality or if they indicate other underlying complexities within the biological system.…”