MIR605 rs2043556 is associated with the occurrence of multiple primary tumors in TP53 p.(Arg337His) mutation carriers
| Autor: | Alexandre Andre Balieiro Anastacio da Costa, Gabriel de Souza Macedo, Cintia Regina Niederauer Ramos, Tiago Finger Andreis, Henrique de Campos Reis Galvão, Edenir Inêz Palmero, Isabel Cristina Bandeira, Maria Isabel Achatz, Patricia Ashton-Prolla, Larissa Brussa Reis, Fernanda Sales Luiz Vianna, Igor Araújo Vieira, Patricia Santos-Silva, Karina Miranda Santiago |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Cancer Research Population Biology medicine.disease_cause Polymorphism Single Nucleotide Germline Li-Fraumeni Syndrome Neoplasms Multiple Primary 03 medical and health sciences 0302 clinical medicine Genotype Genetics medicine Humans Genetic Predisposition to Disease Age of Onset Allele education Molecular Biology Allele frequency Germ-Line Mutation Mutation education.field_of_study medicine.disease Penetrance Founder Effect MicroRNAs Li–Fraumeni syndrome 030220 oncology & carcinogenesis Female Tumor Suppressor Protein p53 Brazil |
| Zdroj: | Cancer Genetics. 240:54-58 |
| ISSN: | 2210-7762 |
| DOI: | 10.1016/j.cancergen.2019.11.005 |
| Popis: | Li-Fraumeni and Li-Fraumeni-like (LFS/LFL) Syndrome are cancer predisposition syndromes caused by germline pathogenic variants in TP53 and are associated with an increased risk of multiple early-onset cancers. In Southern and Southeastern Brazil, a germline founder variant with partial penetrance located in the oligomerization domain of TP53, c.1010G>A p.(Arg337His, commonly known as R337H), has been detected in 0.3% of the general population. Recently, the functional MIR605 variant rs2043556 (A>G) has been identified as a novel LFS phenotype modifier in families with germline TP53 DNA binding variants. In this study, our goal was to verify MIR605 rs2043556 allele frequencies and further explore its possible effects on the phenotype of 238 Brazilian individuals carrying TP53 p.(Arg337His). The MIR605 rs2043556 G allele was detected in 136 (57.1%) individuals, including 25 homozygotes (10.5%), and although it had been previously associated with an earlier mean age of tumor onset, this effect was not observed in this study (p = 0.8). However, in p.(Arg337His) mutation carriers, the GG genotype was significantly associated with the occurrence of multiple primary tumors (p = 0.005). We provide further evidence of MIR605 rs2043556 G allele's effect as a phenotype modulator in carriers of germline TP53 pathogenic variants. |
| Databáze: | OpenAIRE |
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