The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant : Breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium
Moghadasi, Setareh (författare)
Leiden University Medical Centre,Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
Meeks, Huong D. (författare)
University of Utah,Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Ehrencrona, Hans (författare)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, Dept Clin Genet, Lund, Sweden.;Lund Univ, Off Med Serv, Lab Med, Dept Clin Genet, Lund, Sweden.
Paulsson-Karlsson, Ylva (författare)
Uppsala universitet,Uppsala University,Institutionen för immunologi, genetik och patologi
Wappenschmidt, Barbara (författare)
University Hospital of Cologne,Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.;Univ Hosp Cologne, Dept Gynaecol & Obstet, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.;Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany.
Engel, Christoph (författare)
Leipzig University,Univ Leipzig, Inst Med Informat, Leipzig, Germany.;Univ Leipzig, Dept Stat & Epidemiol, Leipzig, Germany.
Gehrig, Andrea (författare)
Julius Maximilian University of Würzburg,Univ Wurzburg, Ctr Familial Breast & Ovarian Canc, Wurzburg, Germany.;Univ Wurzburg, Dept Med Genet, Wurzburg, Germany.;Univ Wurzburg, Inst Human Genet, Wurzburg, Germany.
Arnold, Norbert (författare)
University Medical Center Schleswig-Holstein Campus Kiel,Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynaecol & Obstet, Campus Kiel, Kiel, Germany.
Van Overeem Hansen, Thomas (författare)
University of Copenhagen
Thomassen, Mads (författare)
Odense University Hospital,Odense Univ Hosp, Dept Clin Genet, Odense, Denmark.
Jensen, Uffe Birk (författare)
Aarhus University Hospital,Aarhus Univ Hosp, Dept Clin Genet, Aarhus, Denmark.
Kruse, Torben A (författare)
Odense University Hospital
Ejlertsen, Bent (författare)
University of Copenhagen,Univ Copenhagen, Dept Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Dept Oncol, Copenhagen, Denmark.
Gerdes, Anne-Marie (författare)
University of Copenhagen,Univ Copenhagen, Dept Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Dept Clin Genet, Copenhagen, Denmark.
Pedersen, Inge Søkilde (författare)
Aalborg University
Caputo, Sandrine M. (författare)
Curie Institute, Paris,Inst Curie, Serv Genet, Paris, France.
Couch, Fergus (författare)
Mayo Clinic Minnesota,Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
Hallberg, Emily J. (författare)
Mayo Clinic Minnesota,Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
Background We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers. Methods Data were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium members. A modified segregation analysis was used to calculate BC and OC risks. Relative risks were calculated under both monogenic model and major gene plus polygenic model assumptions. Results In this cohort the cumulative risk of BC and OC by age 70 years was 20% and 6%, respectively. The relative risk for developing cancer was higher when using a model that included the effects of both the R1699Q variant and a residual polygenic component compared with monogenic model (for BC 3.67 vs 2.83, and for OC 6.41 vs 5.83). Conclusion Our results confirm that BRCA1*R1699Q confers an intermediate risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingooophorectomy should be considered based on family history.
Ämnesord
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)