Ovarian and Breast Cancer Risks Associated with Pathogenic Variants in RAD51C and RAD51D
| Autor: | Georgia Chenevix-Trench, Bernd Auber, Douglas F. Easton, Kristiina Aittomäki, Andy C. H. Lee, Ramunas Janavicius, Ana Vega, Paul D.P. Pharoah, Xin Yang, Liisa M. Pelttari, Malene Djursby, Eric Hahnen, Åke Borg, Mark E. Robson, Stephen B. Gruber, Susan J. Ramus, kConFab Investigators, Lisa Golmard, Ian Jacobs, Jill S. Dolinsky, Holly LaDuca, Karin Kast, Clare Turnbull, Fergus J. Couch, W. D. Foulkes, Thomas Hansen, Simon A. Gayther, Allan Jensen, Christoph Engel, Heli Nevanlinna, Ana Osorio, Jacek Gronwald, Judy Garber, Helen Hanson, Susanne K. Kjaer, Julie O. Culver, Goska Leslie, Ed Dicks, Honglin Song, Barbara Rivera, Richard S. Houlston, Anders Kvist, Estrid Høgdall, Antonis C. Antoniou, Dieter Niederacher, Nadia Traficante, Miguel de la Hoya, Rita K. Schmutzler, Alfons Meindl, Judit Horvath, Orland Diez, Adam N. Rosenthal, Laurent Castera, Chey Loveday, David D.L. Bowtell, Joe Dennis, Marc Tischkowitz, Susan M. Domchek, Judith Balmaña, Hans Ehrencrona, Usha Menon |
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| Přispěvatelé: | Leslie, Goska [0000-0001-5756-6222], Dicks, Ed [0000-0002-0617-0401], Lee, Andrew [0000-0003-0677-0252], Dennis, Joe [0000-0003-4591-1214], Easton, Douglas [0000-0003-2444-3247], Tischkowitz, Marc [0000-0002-7880-0628], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, Medicum, Research Programs Unit, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Cancer Research ASCERTAINMENT SAMPLING PROBLEM 0302 clinical medicine 3123 Gynaecology and paediatrics Risk Factors CONFER SUSCEPTIBILITY Young adult Aged 80 and over Ovarian Neoplasms 0303 health sciences medicine.diagnostic_test Articles GERMLINE MUTATIONS Middle Aged 3. Good health DNA-Binding Proteins SUSCEPTIBILITY GENES 030220 oncology & carcinogenesis Female AcademicSubjects/MED00010 Adult medicine.medical_specialty Heterozygote Adolescent Genetic counseling 3122 Cancers Breast Neoplasms 03 medical and health sciences Young Adult Breast cancer Internal medicine medicine Cancer Family Humans Genetic Predisposition to Disease Genetic Testing First-degree relatives Genetic Association Studies Germ-Line Mutation 030304 developmental biology Genetic testing Aged business.industry Cancer Complex segregation analysis medicine.disease BRCA2 MODEL RESOLUTION business |
| Zdroj: | Yang, X, Song, H, Leslie, G, Engel, C, Hahnen, E, Auber, B, Horváth, J, Kast, K, Niederacher, DI, Turnbull, C, Houlston, R, Hanson, H, Loveday, C, Dolinsky, J S, Laduca, H, Ramus, S J, Menon, U, Rosenthal, A N, Jacobs, I, Gayther, S A, DIcks, E, Nevanlinna, H, Aittomäki, K, Pelttari, L M, Ehrencrona, H, Borg, Å, Kvist, A, Rivera, B, Hansen, T V O, Djursby, M, Lee, A, Dennis, J, Bowtell, D D, Traficante, N, DIez, O, Balmaña, J, Gruber, S B, Chenevix-Trench, G, Investigators, K, Jensen, A, Kjær, S K, Høgdall, E, Castéra, L, Garber, J, Janavicius, R, Osorio, A, Golmard, L, Vega, A, Couch, F J, Robson, M, Gronwald, J, Domchek, S M, Culver, J O, De La Hoya, M, Easton, D F, Foulkes, W D, Tischkowitz, M, Meindl, A, Schmutzler, R K, Pharoah, P D P & Antoniou, A C 2020, ' Ovarian and Breast Cancer Risks Associated with Pathogenic Variants in RAD51C and RAD51D ', Journal of the National Cancer Institute, vol. 112, no. 12, pp. 1242-1250 . https://doi.org/10.1093/jnci/djaa030 JNCI Journal of the National Cancer Institute |
| Popis: | Background The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. Methods We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. Results Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% confidence interval [CI] = 5.60 to 10.19; P = 5 × 10-40; RAD51D: RR = 7.60, 95% CI = 5.61 to 10.30; P = 5 × 10-39) and BC (RAD51C: RR = 1.99, 95% CI = 1.39 to 2.85; P = 1.55 × 10-4; RAD51D: RR = 1.83, 95% CI = 1.24 to 2.72; P = .002). For both RAD51C and RAD51D, there was a suggestion that the TOC relative risks increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 years were 11% (95% CI = 6% to 21%) for RAD51C and 13% (95% CI = 7% to 23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 years were 21% (95% CI = 15% to 29%) for RAD51C and 20% (95% CI = 14% to 28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C and RAD51D pathogenic variant carriers varied by cancer family history and could be as high as 32–36% for TOC, for carriers with two first-degree relatives diagnosed with TOC, or 44–46% for BC, for carriers with two first-degree relatives diagnosed with BC. Conclusions These estimates will facilitate the genetic counseling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models. |
| Databáze: | OpenAIRE |
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