Yael Laitman1, Rachel Michaelson-Cohen2, Einat Levi2, Rakefet Chen-Shtoyerman3, Orit Reish4, Sagi Josefsberg Ben-Yehoshua3, Rinat Bernstein-Molho5,6, Lital Keinan-Boker7,8, Ora Rosengarten9, Barbara G Silverman7, Tamar Perri10,6, Jacob Korach10,6, Pnina Mor2, Noa Ephrat Ben-Baruch11, Ephrat Levy Lahad2, Eitan Friedman1,6. 1. Oncogenetics Unit, Institute of Human Genetics, and Meirav High Risk Clinic, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 2. Genetics Institute and NOGA High Risk Clinic, Shaare Zedek Medical Center, Hebrew University School of Medicine, Jerusalem, Israel. 3. Oncogenetics Clinic, Clinical Genetics Institute, Kaplan Medical Center, Rehovot, Hebrew University School of Medicine, Jerusalem, Israel. 4. Genetics Institute, Assaf Harofe Medical Center, Zerifin, Israel. 5. Breast Cancer Unit, Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 6. Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 7. Israeli National Cancer Registry, Ministry of Health, Chaim Sheba Medical Center, Tel-Hashomer, Israel. 8. School of Public Health, University of Haifa, Haifa, Israel. 9. Gyneco-Oncology Unit, Institute of Oncology, Shaare Zedek Medical Center, Hebrew University School of Medicine, Jerusalem, Israel. 10. Department of Gyneco-Oncology, Sheba Medical Center, Tel-Hashomer, Israel. 11. Oncology Department, Kaplan Medical Center, Rehovot, Hebrew University School of Medicine, Jerusalem, Israel.
Abstract
BACKGROUND: BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved. METHOD: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count. RESULTS: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer). CONCLUSION: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers.
BACKGROUND:BRCA1/2 mutation carriers have an increased risk of developing ovarian cancer, leading to the recommendation of risk-reducing salpingo-oophorectomy (RRSO) at 35-40 years of age. The role, if any, that BRCA mutations play in conferring uterine cancer risk, is unresolved. METHOD: Jewish Israeli women, carriers of one of the predominant Jewish mutations in BRCA1/2 from 1998 to 2016, were recruited. Cancer diagnoses were determined through the Israeli National Cancer Registry. Uterine cancer risk was assessed by computing the standardized incidence ratio of observed-to-expected number of cases, using the exact 2-sided P value of Poisson count. RESULTS: Overall, 2627 eligible mutation carriers were recruited from 1998 to 2016, 2312 (88%) of whom were Ashkenazi Jews (1463 BRCA1, 1154 BRCA2 mutation carriers, 10 double mutation carriers). Among these participants, 1310 underwent RRSO without hysterectomy at a mean (± standard deviation) age of 43.6 years (± 4.4 years). During 32,774 women-years of follow up, 14 women developed uterine cancer, and the observed-to-expected rate of all histological subtypes was 3.98 (95% confidence interval [CI], 2.17-6.67; P < .001). For serous papillary (n = 5), the observed-to-expected ratio was 14.29 (95% CI, 4.64-33.34; P < .001), and for sarcoma (n = 4) it was 37.74 (95% CI, 10.28-96.62). These rates were also higher than those detected in a group of 1844 age- and ethnicity-matched women (53% with breast cancer). CONCLUSION: Israeli BRCA1 or BRCA2 mutation carriers are at an increased risk for developing uterine cancer, especially serous papillary and sarcoma. These elevated risks of uterine cancer should be discussed with BRCA carriers.
Authors: Maria Luisa Gasparri; Serena Bellaminutti; Ammad Ahmad Farooqi; Ilaria Cuccu; Violante Di Donato; Andrea Papadia Journal: J Clin Med Date: 2022-05-31 Impact factor: 4.964