Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families

作者：Weang-Kee Ho, Nur Tiara Hassan, Sook‐Yee Yoon, Xin Yang, Joanna Lim, Nur Diana Binte Ishak, Peh Joo Ho, Eldarina Wijaya, Patsy Pei-Sze Ng, Craig Luccarini, Jamie Allen, Mei-Chee Tai, Jianbang Chiang, Zewen Zhang, Mee‐Hoong See, Meow‐Keong Thong, Yin Ling Woo, Alison M. Dunning, Mikael Hartman, Cheng Har Yip, Nur Aishah Mohd Taib, Douglas F. Easton, Jingmei Li, Joanne Ngeow, Antonis C. Antoniou, Soo‐Hwang Teo, Benita Kiat Tee Tan, Su-Ming Tan, Veronique Kiak Mien Tan, Ern Yu Tan, Geok Hoon Lim, Alexis Jiaying Khng, Gaik-Siew Ch’ng, Jamil Omar, Chee-Meng Yong, Ismail Aliyas, Rozita Abdul Malik, Suguna Subramaniam, Wee-Wee Sim, Chun Sen Lim, S.C. Lee, K. P. Lim, Mohamad Nasir Shafiee, Fuad Ismail, Mohd Pazudin Ismail, Mohamad Faiz Mohamed Jamli, Suresh Kumarasamy, J.S.H. Low, Ahmad Muzamir Ahmad Mustafa, M.J. Makanjang, Shahila Taib, N.L.C. Cheah, Chee Kin Fong, Kean-Fatt Ho, Azura Deniel, Soo Fan Ang, Ahmad Radzi Ahmad Badruddin, Lye-Mun Tho · 发表于：The Lancet Regional Health - Western Pacific · 年份：2024 · DOI：10.1016/j.lanwpc.2024.101017 · 被引用次数：9 · 研究领域：BRCA gene mutations in cancer、Multiple and Secondary Primary Cancers、PARP inhibition in cancer therapy

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 BRCA 2. 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...