Homologous Recombination Repair Polymorphisms, Cancer Susceptibility and Treatment Outcome

Goričar, Katja; Dolžan, Vita

doi:10.5772/59729

Cited by 2 publications

(2 citation statements)

References 114 publications

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“…The Spanish patients came from the Hospital University La Paz Madrid, the Hospital University Donostia and the Department of Genetics, Physical Anthropology and Animal Physiology of UPV/EHU. The Slovenian patients were diagnosed at the Department of Hematology and Oncology, University Children's Hospital, Ljubljana, Slovenia, or at the Institute of Oncology, Ljubljana, Slovenia (18). All cases were diagnosed by experienced pathologists and oncologists.…”

Section: Association Studymentioning

confidence: 99%

A systematic review and meta-analysis of MDM2 polymorphisms in osteosarcoma susceptibility

et al. 2016

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Two polymorphisms in the murine double minute 2 (MDM2) gene (rs1690916 and rs2279744) have been associated with the risk of osteosarcoma (OS). When we analyzed these two polymorphisms in two new independents cohorts (Spanish and Slovenian), we found no association. In order to clarify this, we conducted a meta-analysis including six populations, with a total of 246 OS patients and 1,760 controls for rs1690916; and 433 OS patients and 1,959 controls for rs2279744. Pooled odds ratio risks and corresponding 95% CI were estimated to assess the possible associations. Our results showed that these two polymorphisms were not associated with the susceptibility of OS under any genetic model studied. In conclusion, the present meta-analysis indicates that MDM2 rs1690916 and rs2279744 cannot be considered as genetic risk factors for OS susceptibility in the different populations. Therefore, the influence of these two polymorphisms on the risk of OS may be less important than previously suggested. Future studies are needed to confirm these results.O steosarcoma (OS) is the most common primary malignant tumor of bone, mainly occurring in the second decade of life. The precise etiology of the disease remains partially unknown (1). Nevertheless, genetic factors might play a key role in its pathogenesis (2). To date diverse studies have reported associations of common genetic variants in biologically plausible pathways with OS risk (3-6). Among the analyzed variants, rs1690916 and rs2279744 in the murine double minute 2 gene (MDM2) are two of the most recurrently studied and associated with the susceptibility of OS (5,7-9). The MDM2 gene is especially interesting because it functions as an E3 ubiquitin ligase promoting p53 degradation (10,11).MDM2 rs1690916, located at the 3′ untranslated region of the gene, was significantly associated with the risk of OS in a large North-American population including 96 patients and 1,416 controls (7). They found that rs1690916 AA genotype decreased the risk of the disease. rs1690916 A allele was also found to be associated with a decreased risk of bone tumors in Russian population including 68 patients and 86 controls (9). However, this study only included 26 OS patients out of 68 analyzed. MDM2 rs2279744, situated in the promoter region, was related to an increased risk of OS (GG vs. TT) in Italian population (211 OS patients and 250 controls) (5), being this association stronger in females. Moreover, a robust correlation between rs2279744 G allele enrichment and MDM2 amplification was found, suggesting the contribution of this polymorphism to OS tumorigenesis (12). However, this single nucleotide polymorphism (SNP) did not show any association in the North-American population (7). A meta-analysis evaluating the association between these two polymorphisms and the risk of OS was performed, concluding that both SNPs influence the risk of OS (13). Nevertheless, some inaccuracies were detected in the study. Among others, the lack of information in the methods used to select the studies and extr...

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Section: Association Studymentioning

confidence: 99%

A systematic review and meta-analysis of MDM2 polymorphisms in osteosarcoma susceptibility

et al. 2016

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“…Genomic DNA was isolated from two to three cores (1 mm in diameter) of histologically confirmed normal tissue using QIAamp DNA Mini kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions (Goricar et al, 2014). Genotyping of REV1 rs3087403 (p.Val138Met), rs3087386 (p.Phe257Ser), and rs3087399 (p.Asn373Ser) and REV3L rs462779 (p.Thr1224Ile), rs455732 (p.Val1430 = ), rs3204953 (p.Val3064Ile), rs465646 (c.*461C > T) tag SNPs (Goricar et al, 2015) was performed using KASPar assay. Genotyping was repeated in 20% samples to check for genotyping accuracy.…”

Section: Dna Extraction and Genotypingmentioning

confidence: 99%

Translesion Polymerase Genes Polymorphisms and Haplotypes Influence Survival of Osteosarcoma Patients

Goričar

Kovač

Jazbec

et al. 2015

OMICS: A Journal of Integrative Biology

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Cytotoxic activity of most chemotherapeutic agents is based on their ability to induce DNA damage. Interstrand crosslinks are among the most detrimental forms of DNA damage as both DNA strands are affected. As translesion polymerases participate in their repair, they may be important for response to chemotherapeutic agents that induce such lesions, including commonly used cisplatin. Altered expression of translesion polymerase genes REV1 and REV3L may modify sensitivity to cisplatin. As osteosarcoma patients are commonly treated with cisplatin-based chemotherapy, our aim was to investigate if REV1 and REV3L polymorphisms influence survival of osteosarcoma patients treated with cisplatin-based chemotherapy. We determined the genotypes of common functional tag REV1 and REV3L polymorphisms in 66 osteosarcoma patients. Cox regression was used for survival analysis. Carriers of at least one polymorphic REV1 rs3087403 allele had significantly shorter EFS and overall survival (OS) ( p = 0.004; HR = 3.79; 95%CI = 1.53-9.35 and p < 0.001; HR = 4.44; 95%CI = 1.92-10.27, respectively). Combination of REV1 rs3087403 and REV3L rs462779 polymorphisms was also significantly associated with shorter OS (p trend < 0.001) and shorter EFS (p trend = 0.003). The results of this first study on polymorphisms in translesion polymerase genes in osteosarcoma suggest they could help predict outcome of cisplatin-based chemotherapy in osteosarcoma patients.

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Homologous Recombination Repair Polymorphisms, Cancer Susceptibility and Treatment Outcome

Cited by 2 publications

References 114 publications

A systematic review and meta-analysis of MDM2 polymorphisms in osteosarcoma susceptibility

A systematic review and meta-analysis of MDM2 polymorphisms in osteosarcoma susceptibility

Translesion Polymerase Genes Polymorphisms and Haplotypes Influence Survival of Osteosarcoma Patients

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