Age-specific breast and ovarian cancer risks associated with germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variants - an Asian study of 572 families.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 38333895.
- Also identified by DOI 10.1016/j.lanwpc.2024.101017 and PMC identifier 10851205.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Clinical management of Asian <i>BRCA1</i> and <i>BRCA2</i> 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. Data were collected on 271 <i>BRCA1</i> and 301 <i>BRCA2</i> 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. BC and OC relative risks (RRs) varied across age groups for both <i>BRCA1</i> and <i>BRCA</i>2. The age-specific RR estimates were similar across ethnicities and country of residence. For <i>BRCA1</i> 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 <i>BRCA2</i> 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 <i>BRCA1,</i> and between 43 and 47% for <i>BRCA2</i> carriers. The cumulative risk of OC by age 80 was 31% (27-36%) for <i>BRCA1</i> and 12% (10%-15%) for <i>BRCA2</i> carriers in Malaysia born between 1950 and 1959; and 42% (34-50%) for <i>BRCA1</i> and 20% (14-27%) for <i>BRCA2</i> 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<sup>-5</sup> for <i>BRCA1</i> and 0.018 for <i>BRCA</i>2). 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. Wellcome Trust [grant no: v203477/Z/16/Z]; CRUK (PPRPGM-Nov20∖100002).