دورية أكاديمية
The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
| العنوان: | The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor |
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| المؤلفون: | Brandao, A, Paulo, P, Maia, S, Pinheiro, M, Peixoto, A, Cardoso, M, Silva, MP, Santos, C, Eeles, RA, Kote-Jarai, Z, Muir, K, Schleutker, J, Wang, Y, Pashayan, N, Batra, J, Gronberg, H, Neal, DE, Nordestgaard, BG, Tangen, CM, Southey, MC, Wolk, A, Albanes, D, Haiman, CA, Travis, RC, Stanford, JL, Mucci, LA, West, CML, Nielsen, SF, Kibel, AS, Cussenot, O, Berndt, SI, Koutros, S, Sorensen, KD, Cybulski, C, Grindedal, EM, Park, JY, Ingles, SA, Maier, C, Hamilton, RJ, Rosenstein, BS, Vega, A, Kogevinas, M, Wiklund, F, Penney, KL, Brenner, H, John, EM, Kaneva, R, Logothetis, CJ, Neuhausen, SL, De Ruyck, K, Razack, A, Newcomb, LF, Lessel, D, Usmani, N, Claessens, F, Gago-Dominguez, M, Townsend, PA, Roobol, MJ, Teixeira, MR |
| بيانات النشر: | MDPI |
| سنة النشر: | 2020 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2072-6694 |
| العلاقة: | pii: cancers12113254; Brandao, A., Paulo, P., Maia, S., Pinheiro, M., Peixoto, A., Cardoso, M., Silva, M. P., Santos, C., Eeles, R. A., Kote-Jarai, Z., Muir, K., Schleutker, J., Wang, Y., Pashayan, N., Batra, J., Gronberg, H., Neal, D. E., Nordestgaard, B. G., Tangen, C. M. ,. Teixeira, M. R. (2020). The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor. CANCERS, 12 (11), https://doi.org/10.3390/cancers12113254Test.; http://hdl.handle.net/11343/304503Test |
| الإتاحة: | https://doi.org/10.3390/cancers12113254Test http://hdl.handle.net/11343/304503Test |
| حقوق: | CC BY ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.B59CD0EA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20726694 |
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