Association of common variants in MTAP with susceptibility and overall survival of osteosarcoma: a two-stage population-based study in Han Chinese

Abstract

Osteosarcoma (OS) is a common malignant tumor, which exists widely in the bone of children and adolescents, and genetic factors may influence its susceptibility. Recently, the gene MTAP has been reported to be associated with OS in a Caucasian population. To investigate the association of common variants in MTAP with OS risk in Han Chinese individuals, we designed a two-stage case-control study with 392 OS patients and 1,578 unrelated healthy controls of Han Chinese individuals. A total of 17 tagging single nucleotide polymorphisms (SNPs) were firstly genotyped in the discovery stage, and single-SNP association and haplotypic association analyses have been performed. The SNP rs7023329 was found to be strongly associated with the OS risk (adjusted P = 0.002908), and the results of odds ratios (ORs) and 95% confidence intervals (CI) revealed increased risks from A allele of the SNP on OS (OR=1.33, 95% CI=1.13-1.62). The results were confirmed with a similar pattern in the validation stage (adjusted P = 0.006737, OR=1.49, 95% CI=1.11-2.00). Moreover, haplotypic analyses indicated that one haplotype block containing rs7023329 was significantly associated with OS risk in both stages (both global P<0.0001). The statistically significant association between the rs7023329 genotype and poor survival in OS patients was also observed. To sum up, our results prove that MTAP plays an important role in the etiology of OS, suggesting this gene as a potential genetic modifier for OS development.

MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation

“…However, studies have shown that germline mutations in MTAP result in an autosomal-dominant bone cancer syndrome, and that MTAP knockout, independent of CDKN2A deletion, promotes lymphoma in mice (3)(4)(5). MTAP deficiency has also been independently associated with poor clinical outcomes in patients of several cancer types (6)(7)(8)(9).…”

Epidemiological Evidence for Associations Between Genetic Variants and Osteosarcoma Susceptibility: A Meta-Analysis

“…Our metaanalysis also presented strong evidence that MTAP rs7023329 (under allelic and dominant model) and rs7027989 (under the allelic model) were associated with a lower risk of OS in Asians. Although the exact mechanism of SNP rs7023329 affect OS risk remains unknown, Zhi et al hypothesized that SNP rs7023329 might coexist in linkage disequilibrium with one certain variants and affect its regulation machinery to associate with OS risk (42). The protein kinase C gamma (PRKCG) gene is located on chromosome 19q13.42 and functions as the major receptor for tumor promoters.…”

“…Although the exact mechanism of SNP rs7023329 affect OS risk remains unknown, Zhi et al. hypothesized that SNP rs7023329 might coexist in linkage disequilibrium with one certain variants and affect its regulation machinery to associate with OS risk ( 42 ). The protein kinase C gamma ( PRKCG ) gene is located on chromosome 19q13.42 and functions as the major receptor for tumor promoters.…”

Long Non-Coding RNA ANRIL as a Potential Biomarker of Chemosensitivity and Clinical Outcomes in Osteosarcoma

“…We carefully designed our ANRIL modification experiments to only target ANRIL and showed that there were no significant gene expression changes in three neighboring protein-coding genes. Previously, one of these nearby protein-coding genes ( MTAP ) was identified in osteosarcoma [ 62 ]. It is thought to play a role in cancer cell etiology given its behavior as a tumor suppressor [ 62 , 63 , 64 , 65 ].…”

“…Previously, one of these nearby protein-coding genes ( MTAP ) was identified in osteosarcoma [ 62 ]. It is thought to play a role in cancer cell etiology given its behavior as a tumor suppressor [ 62 , 63 , 64 , 65 ]. However, correlation analyses between the expression of MTAP and cisplatin and doxorubicin sensitivity found no relationship between them.…”