Abstract C060: The spectrum of germline mutation carriers in a cohort of breast and ovarian cancer patients in the Caribbean
Bibliographic record
Abstract
Abstract The Caribbean population is predominantly of African descent with an admixture of Indigenous, East Asian, Indian subcontinent, Western European and Middle Eastern descendants. This region has one of the highest burdens of cancer in the world, and breast cancer is the leading cause of cancer death in Caribbean women. We established a cohort of 1,019 people diagnosed with breast and ovarian cancer across 7 Caribbean countries (Cayman Islands, Bahamas, Barbados, Dominica, Haiti, Jamaica, Trinidad and Tobago)—Caribbean Women's Cancer Study (CWCS). The primary objective was to identify deleterious mutations in the breast cancer genes in a cohort of Caribbean people with breast and/or ovarian cancer. Methods: The study was conducted between 2004-2015 in the Bahamas, Cayman Islands, Jamaica, Barbados, Dominica, Trinidad and Tobago and Haiti. Following IRB approval, 1,019 women and men diagnosed with breast or ovarian cancer were identified through outpatient oncology clinicals, treating physicians and cancer societies on the islands. In addition, participants were recruited through radio, newspaper and TV advertisements. Inclusion criteria were pathologic diagnosis of breast (male or female) and/or ovarian cancer, at least 1 grandparent born in one of the participating countries and ability to provide saliva. NGS and MPLA (BRCA1/2) were performed on a panel of 31 genes. The following epidemiologic and anthropometric measures were collected: family pedigree; age of menarche, menopause, and first pregnancy; number of pregnancies; number of siblings; year of birth; age at cancer diagnosis; body mass index (BMI) at time of diagnosis; stage of cancer; mode of diagnosis; and tumor characteristics. Results: The mean age of the mutation carriers was 45 (20-70) years and mean BMI was 29.0. 70% of the mutation carriers self-identified as Afro-Caribbean. 75% identified their cancer by palpation. The Bahamas has the highest incidence of hereditary breast cancer in the world due to founder mutations in the BRCA1 and BRCA2 genes (23% of unselected breast cancer). In Trinidad and Tobago 12% of women with breast cancer had a mutation in BRCA1/2, PALB2, RAD51C or CHEK2. Jamaica had 4.9% incidence of BRCA1/2, STK11, NBN and PALB2 mutations and 6.9% (5/94) of Haitian women have deleterious mutations in BRCA1/2, PALB2. In Barbados 17.9% (16/89) have deleterious mutations in BRCA1/2, PALB2. In Dominica (4/57) 8.8% of the cohort had BRCA2 or PALB2 deleterious mutations and 6.3% (4/63) in the Cayman Islands had a deleterious mutation in ATM, BRCA1/2. 64% of mutations carriers had a frameshift, nonsense, or large deletion in BRCA1, 23% in BRCA2 and 9% in PALB2. There were 29 unique mutations in BRCA1 in 92 individuals (64%) and 23 unique mutations in BRCA2 with recurring (founder) mutations predominantly in the Bahamas. 11 distinct mutations in PALB2 were seen in 13 individuals across 5 countries. Conclusion: This initial Caribbean population-based study demonstrates that genetic causes of breast cancer are common in the Caribbean population. Citation Format: Sophia H.L. George, Talia Donenberg, Cheryl Alexis, Vincent DeGennaro, Hedda Dyer, Sook Yin, Priscila Barreto-Coelho, Simonnette Thompson, Raleigh Butler, Gillian Wharfe, Jameel Ali, Theodore Turnquest, DuVaughn Curling, Mohammad Akbari, Steven Narod, Judith Hurley. The spectrum of germline mutation carriers in a cohort of breast and ovarian cancer patients in the Caribbean [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C060.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".