Ho, Weang-Kee and Hassan, Nur Tiara and Yoon, Sook-Yee and Yang, Xin and Lim, Joanna M.C. and Binte Ishak, Nur Diana and Ho, Peh Joo and Wijaya, Eldarina A. and Ng, Patsy Pei-Sze and Luccarini, Craig and Allen, Jamie and Tai, Mei-Chee and Chiang, Jianbang and Zhang, Zewen and See, Mee-Hoong and Thong, Meow-Keong and Woo, Yin-Ling and Dunning, Alison M. and Hartman, Mikael and Yip, Cheng-Har and Mohd Taib, Nur Aishah and Easton, Douglas F. and Li, Jingmei and Ngeow, Joanne and Antoniou, Antonis C. and Teo, Soo-Hwang (2024) Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families. Lancet Regional Health-Western Pacific, 44. p. 101017. ISSN 2666-6065, DOI https://doi.org/10.1016/j.lanwpc.2024.101017.
Full text not available from this repository.Abstract
Background: Clinical management of Asian BRCA1 and BRCA2 pathogenic variants (PV) carriers remains challenging due to imprecise age-specific breast (BC) and ovarian cancer (OC) risks estimates. We aimed to refine these estimates using six multi-ethnic studies in Asia. Methods: Data were collected on 271 BRCA1 and 301 BRCA2 families from Malaysia and Singapore, ascertained through population/hospital-based case-series (88) and genetic clinics (12). Age-specific cancer risks were estimated using a modified segregation analysis method, adjusted for ascertainment. Findings: BC and OC relative risks (RRs) varied across age groups for both BRCA1 and BRCA2. The age-specific RR estimates were similar across ethnicities and country of residence. For BRCA1 carriers of Malay, Indian and Chinese ancestry born between 1950 and 1959 in Malaysia, the cumulative risk (95 CI) of BC by age 80 was 40 (36–44), 49 (44–53) and 55 (51–60), respectively. The corresponding estimates for BRCA2 were 29 (26–32), 36 (33–40) and 42 (38–45). The corresponding cumulative BC risks for Singapore residents from the same birth cohort, where the underlying population cancer incidences are higher compared to Malaysia, were higher, varying by ancestry group between 57 and 61 for BRCA1, and between 43 and 47 for BRCA2 carriers. The cumulative risk of OC by age 80 was 31 (27–36) for BRCA1 and 12 (10–15) for BRCA2 carriers in Malaysia born between 1950 and 1959; and 42 (34–50) for BRCA1 and 20 (14–27) for BRCA2 carriers of the same birth cohort in Singapore. There was evidence of increased BC and OC risks for women from >1960 birth cohorts (p-value = 3.6 × 10−5 for BRCA1 and 0.018 for BRCA2). Interpretation: The absolute age-specific cancer risks of Asian carriers vary depending on the underlying population-specific cancer incidences, and hence should be customised to allow for more accurate cancer risk management. Funding: Wellcome Trust grant no: v203477/Z/16/Z; CRUK (PPRPGM-Nov20∖100002). © 2024 The Author(s)
| Item Type: | Article |
|---|---|
| Funders: | National Research Foundation Singapore, Clinician Scientist Award (NMRC/CSA-INV/0017/2017); (MOH-000654), National Medical Research Council, Singapore, National Cancer Centre Research Fund (NCCRF-YR2018-NOV-1), Terry Fox Foundation, Canada, National Research Foundation, Singapore, through the Singapore Ministry of Health's National Medical Research Council, Precision Health Research, Singapore (PRECISE), under PRECISE's Clinical Implementation Pilot grant scheme |
| Additional Information: | Cited by: 0; All Open Access, Gold Open Access |
| Uncontrolled Keywords: | BRCA1 protein; BRCA2 protein; adult; age specific breast cancer; age specific ovarian cancer; aged; ancestry group; Article; Asian; birth cohort; breast cancer; cancer incidence; cancer risk; cohort analysis; cumulative cancer risk; ethnicity; female; genetic variability; germline pathogenic variant; heterozygote; human; malignant neoplasm; middle aged; ovary cancer; very elderly; young adult |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Obstetrics & Gynaecology Department Faculty of Medicine > Surgery Department Universiti Malaya Medical Centre (UMMC) |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 15 Nov 2024 08:25 |
| Last Modified: | 15 Nov 2024 08:25 |
| URI: | http://eprints.um.edu.my/id/eprint/44777 |
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