Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks
| العنوان: | Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks |
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| المؤلفون: | Decker, Brennan, Allen, Jamie, Luccarini, Craig, Pooley, Karen A, Shah, Mitul, Bolla, Manjeet K, Wang, Qin, Ahmed, Shahana, Baynes, Caroline, Conroy, Don M, Brown, Judith, Luben, Robert, Ostrander, Elaine A, Pharoah, Paul DP, Dunning, Alison M, Easton, Douglas F |
| المصدر: | Journal of Medical Genetics |
| بيانات النشر: | BMJ Publishing Group, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Cancer: breast, Genetic Variation, Breast Neoplasms, Ataxia Telangiectasia Mutated Proteins, DNA-Binding Proteins, Checkpoint Kinase 2, Evidence Based Practice, Sequence Analysis, Protein, Genetic Epidemiology, Cancer Genetics, Humans, Female, Genetic Predisposition to Disease, Fanconi Anemia Complementation Group N Protein, Geneticscreening/counselling |
| الوصف: | Background Breast cancer (BC) is the most common malignancy in women and has a major heritable component. The risks associated with most rare susceptibility variants are not well estimated. To better characterise the contribution of variants in ATM, CHEK2, PALB2 and XRCC2, we sequenced their coding regions in 13 087 BC cases and 5488 controls from East Anglia, UK. Methods Gene coding regions were enriched via PCR, sequenced, variant called and filtered for quality. ORs for BC risk were estimated separately for carriers of truncating variants and of rare missense variants, which were further subdivided by functional domain and pathogenicity as predicted by four in silico algorithms. Results Truncating variants in PALB2 (OR=4.69, 95% CI 2.27 to 9.68), ATM (OR=3.26; 95% CI 1.82 to 6.46) and CHEK2 (OR=3.11; 95% CI 2.15 to 4.69), but not XRCC2 (OR=0.94; 95% CI 0.26 to 4.19) were associated with increased BC risk. Truncating variants in ATM and CHEK2 were more strongly associated with risk of oestrogen receptor (ER)-positive than ER-negative disease, while those in PALB2 were associated with similar risks for both subtypes. There was also some evidence that missense variants in ATM, CHEK2 and PALB2 may contribute to BC risk, but larger studies are necessary to quantify the magnitude of this effect. Conclusions Truncating variants in PALB2 are associated with a higher risk of BC than those in ATM or CHEK2. A substantial risk of BC due to truncating XRCC2 variants can be excluded. |
| اللغة: | English |
| تدمد: | 1468-6244 0022-2593 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::f66a7d8767bcda142e70616465225747Test http://europepmc.org/articles/PMC5740532Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........f66a7d8767bcda142e70616465225747 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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