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: | Manuela Gago-Dominguez, Karina Dalsgaard Sørensen, Radka Kaneva, Canary Pass Investigators, Rosalind A. Eeles, Stella Koutros, Kim De Ruyck, Sonja I. Berndt, Manolis Kogevinas, Sofia Maia, Eli Marie Grindedal, Christopher J. Logothetis, Davor Lessel, Nora Pashayan, Ana Peixoto, Catarina Santos, Nawaid Usmani, Zsofia Kote-Jarai, Olivier Cussenot, Esther M. John, Christopher A. Haiman, Catherine M. Tangen, Jong Y. Park, Lorelei A. Mucci, Johanna Schleutker, Ruth C. Travis, Andreia Brandão, Sune F. Nielsen, Manuel R. Teixeira, Melissa C. Southey, Ana Vega, Adam S. Kibel, Ying Wang, Børge G. Nordestgaard, Cezary Cybulski, Jyotsna Batra, Kenneth Muir, Henrik Grönberg, Janet L. Stanford, Lisa F. Newcomb, Hermann Brenner, Manuela Pinheiro, Apcb BioResource, David E. Neal, Marta Cardoso, Paula Paulo, Barry S. Rosenstein, Monique J. Roobol, Robert J. Hamilton, Catharine M L West, Frank Claessens, Paul A. Townsend, Kathryn L. Penney, Susan L. Neuhausen, Alicja Wolk, Christiane Maier, Demetrius Albanes, Fredrik Wiklund, Maria P. Silva, Azad Hassan Abdul Razack, Sue A. Ingles |
| المساهمون: | Urology, Brandão, Andreia [0000-0003-0938-1543], Eeles, Rosalind A [0000-0002-3698-6241], Muir, Kenneth [0000-0001-6429-988X], Schleutker, Johanna [0000-0002-1863-0305], Wang, Ying [0000-0002-1241-6252], Pashayan, Nora [0000-0003-0843-2468], Nordestgaard, Børge G [0000-0002-1954-7220], Sørensen, Karina Dalsgaard [0000-0002-4902-5490], Cybulski, Cezary [0000-0002-2819-3057], Park, Jong Y [0000-0002-6384-6447], Wiklund, Fredrik [0000-0002-4623-0544], Brenner, Hermann [0000-0002-6129-1572], Lessel, Davor [0000-0003-4496-244X], Gago-Dominguez, Manuela [0000-0001-6713-4351], Roobol, Monique J [0000-0001-6967-1708], Teixeira, Manuel R [0000-0002-4896-5982], Apollo - University of Cambridge Repository |
| المصدر: | Brandão, A, Paulo, P, Maia, S, Pinheiro, M, Peixoto, A, Cardoso, M, Silva, M P, Santos, C, Eeles, R A, Kote-Jarai, Z, Muir, K, Ukgpcs Collaborators, Schleutker, J, Wang, Y, Pashayan, N, Batra, J, Apcb BioResource, Grönberg, H, Neal, D E, Nordestgaard, B G, Tangen, C M, Southey, M C, Wolk, A, Albanes, D, Haiman, C A, Travis, R C, Stanford, J L, Mucci, L A, West, C M L, Nielsen, S F, Kibel, A S, Cussenot, O, Berndt, S I, Koutros, S, Sørensen, K D, Cybulski, C, Grindedal, E M, Park, J Y, Ingles, S A, Maier, C, Hamilton, R J, Rosenstein, B S, Vega, A, Kogevinas, M, Wiklund, F, Penney, K L, Brenner, H, John, E M, Kaneva, R, The Profile Study Steering Committee, The Impact Study Steering Committee And Collaborators & The PRACTICAL Consortium 2020, ' The CHEK2 Variant C.349A >G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor ', Cancers, vol. 12, no. 11 . https://doi.org/10.3390/cancers12113254Test Cancers, 12(11):3254, 1-17. Multidisciplinary Digital Publishing Institute (MDPI) Brandão, 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, Grönberg, H, Neal, D E, Nordestgaard, B G, Tangen, C M, Southey, M C, Wolk, A, Albanes, D, Haiman, C A, Travis, R C, Stanford, J L, Mucci, L A, West, C M L, Nielsen, S F, Kibel, A S, Cussenot, O, Berndt, S I, Koutros, S, Sørensen, K D, Cybulski, C, Grindedal, E M, Park, J Y, Ingles, S A, Maier, C, Hamilton, R J, Rosenstein, B S, Vega, A, Kogevinas, M, Wiklund, F, Penney, K L, Brenner, H, John, E M, Kaneva, R, Logothetis, C J, Neuhausen, S L, De Ruyck, K, UKGPCS Collaborators, The Profile Study Steering Committee & The Practical Consortium 2020, ' The CHEK2 variant C.349A >G is associated with prostate cancer risk and carriers share a common ancestor ', Cancers, vol. 12, no. 11, 3254, pp. 1-17 . https://doi.org/10.3390/cancers12113254Test Brandão, A, Paulo, P, Maia, S, Pinheiro, M, Peixoto, A, Cardoso, M, Silva, M P, Santos, C, Eeles, R A, Kote-Jarai, Z, Muir, K, Ukgpcs Collaborators, Schleutker, J, Wang, Y, Pashayan, N, Batra, J, Apcb BioResource, Grönberg, H, Neal, D E, Nordestgaard, B G, Tangen, C M, Southey, M C, Wolk, A, Albanes, D, Haiman, C A, Travis, R C, Stanford, J L, Mucci, L A, West, C M L, Nielsen, S F, Kibel, A S, Cussenot, O, Berndt, S I, Koutros, S, Sørensen, K D, Cybulski, C, Grindedal, E M, Park, J Y, Ingles, S A, Maier, C, Hamilton, R J, Rosenstein, B S, Vega, A, The Impact Study Steering Committee And Collaborators, Kogevinas, M, Wiklund, F, Penney, K L, Brenner, H, John, E M, Kaneva, R, Logothetis, C J, Neuhausen, S L, Ruyck, K D, Razack, A, Newcomb, L F, Canary Pass Investigators, Lessel, D, Usmani, N, Claessens, F, Gago-Dominguez, M, Townsend, P A, Roobol, M J, The Profile Study Steering Committee, The Practical Consortium & Teixeira, M R 2020, ' The CHEK2 Variant C.349A >G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor ', Cancers, vol. 12, no. 11, 3254, pp. 1-17 . https://doi.org/10.3390/cancers12113254Test Cancers, Vol 12, Iss 3254, p 3254 (2020) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute (MDPI), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, SUSCEPTIBILITY LOCI, Cancer-Predisposing Gene, ancer predisposition, cancer predisposition, Biology, WHOLE-GENOME ASSOCIATION, CHEK2-ASTERISK-1100DELC, lcsh:RC254-282, G84E GERMLINE MUTATION, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, medicine, BREAST-CANCER, Missense mutation, CHEK2, METAANALYSIS, Prostate cancer risk, Genetics, Cancer och onkologi, Science & Technology, founder variant, Manchester Cancer Research Centre, MISMATCH REPAIR GENES, ResearchInstitutes_Networks_Beacons/mcrc, Haplotype, 1100DELC, HOXB13, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, prostate cancer, BRCA2, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Relative risk, Cancer and Oncology, Life Sciences & Biomedicine, SNP array |
| 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. We thank the funding support from IPO-Porto Research Center (CI-IPOP-16-2012) and from Fundação para a Ciência e a Tecnologia (FCT; PEst-OE/SAU/ UI0776/2014 and PTDC/DTP-PIC/1308/2014). The following authors were awarded with grants from FCT: PPa (UID/DTP/00776/2013/POCI-01-0145-FEDER-006868), SM (SFRH/BD/71397/2010) and PPi (SFRH/BD/73719/2010). The PRACTICAL consortium (http://practical.icr.ac.ukTest/) was supported by the Canadian Institutes of Health Research, European Commission’s Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148537-01 (the GAME-ON initiative). Genotyping of the OncoArray was funded by the US National Institutes of Health (NIH) [U19 CA 148537 for ELucidating Loci Involved in Prostate cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I] and by Cancer Research UK grant A8197/A16565. Additional analytic support was provided by NIH NCI U01 CA188392 (PI: Schumacher). We would also like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now PCUK), The Orchid Cancer Appeal, Rosetrees Trust, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, NIHR funding to the Manchester Biomedical Research Centre and the Manchester Academic Health Sciences Centre. |
| وصف الملف: | application/pdf; text/xml; application/zip; Electronic |
| اللغة: | English |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::caa7e985f8a0fe4e419e9f130d57a7a2Test https://pure.eur.nl/en/publications/26a68a81-047d-4d67-8d2b-5cb1b3b826caTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....caa7e985f8a0fe4e419e9f130d57a7a2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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