Variants in the ATM-CHEK2-BRCA1 Axis Determine Genetic Predisposition and Clinical Presentation of Papillary Thyroid Carcinoma
| Autor: | Wójcicka, Anna, Czetwertyńska, Małgorzata, Œwierniak, Michał, Długosińska, Joanna, Maciąg, Monika, Czajka, Agnieszka, Dymecka, Kinga, Kubiak, Anna, Kot, Adam, Płoski, Rafał, de la Chapelle, Albert, Jażdżewski, Krystian |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male endocrine system diseases BRCA1 Protein Carcinoma Genetic Variation Ataxia Telangiectasia Mutated Proteins Middle Aged Polymorphism Single Nucleotide Article Carcinoma Papillary White People Checkpoint Kinase 2 Thyroid Cancer Papillary Humans Female Genetic Predisposition to Disease Thyroid Neoplasms skin and connective tissue diseases Genetic Association Studies |
| Popis: | The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6-fold in first-degree relatives of PTC patients. The familial risk could be explained by high-penetrance mutations in yet unidentified genes, or polygenic action of low-penetrance alleles. Since the DNA-damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low-penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR = 2.2, P = 2.37e-10) and BRCA1 rs16941 (odds ratio [OR] = 1.16, P = 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P = 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P = 0.007), N status (P = 0.05), and stage (P = 0.035). Our findings implicate an important role of variants in the ATM- CHEK2- BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations. |
| Databáze: | OpenAIRE |
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