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. 2021 Mar 1;4(3):e210307.
doi: 10.1001/jamanetworkopen.2021.0307.

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean

Sophia H L George  1   2   3 , Talia Donenberg  2   3   4 , Cheryl Alexis  5 , Vincent DeGennaro Jr  6 , Hedda Dyer  7 , Sook Yin  8 , Jameel Ali  9 , Raleigh Butler  10 , Sheray N Chin  11 , DuVaughn Curling  10 , Dwight Lowe  11 , John Lunn  10 , Theodore Turnquest  10 , Gilian Wharfe  11 , Danielle Cerbon  2   12 , Priscila Barreto-Coelho  2   12 , Matthew P Schlumbrecht  1   2   3 , Mohammad R Akbari  13 , Steven A Narod  13 , Judith E Hurley  2   3   12
Affiliations

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean

Sophia H L George et al. JAMA Netw Open. .

Abstract

Importance: Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population.

Objective: To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English- and Creole-speaking Caribbean populations.

Design, setting, and participants: This multisite genetic association study used data from germline genetic test results between June 2010 and June 2018 in the Bahamas, Cayman Islands, Barbados, Dominica, Jamaica, Haiti, and Trinidad and Tobago. Next-generation sequencing on a panel of 30 genes and multiplex ligation-dependent probe amplification (BRCA1 and BRCA2) were performed. Medical records were reviewed at time of study enrollment. Women and men diagnosed with breast and ovarian cancer with at least 1 grandparent born in the participating study sites were included; 1018 individuals were eligible and consented to participate in this study. Data were analyzed from November 4, 2019, to May 6, 2020.

Exposures: Breast and/or ovarian cancer diagnosis.

Main outcomes and measures: Rate of inherited breast and ovarian cancer syndrome and spectrum and types of variants.

Results: Of 1018 participants, 999 (98.1%) had breast cancer (mean [SD] age, 46.6 [10.8] years) and 21 (2.1%) had ovarian cancer (mean [SD] age, 47.6 [13.5] years). Three individuals declined to have their results reported. A total of 144 of 1015 (14.2%) had a pathogenic or likely pathogenic (P/LP) variant in a hereditary breast and ovarian cancer syndrome gene. A total of 64% of variant carriers had P/LP variant in BRCA1, 23% in BRCA2, 9% in PALB2 and 4% in RAD51C, CHEK2, ATM, STK11 and NBN. The mean (SD) age of variant carriers was 40.7 (9.2) compared with 47.5 (10.7) years in noncarriers. Individuals in the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%), followed by Barbados (17.9%), Trinidad (12%), Dominica (8.8%), Haiti (6.7%), Cayman Islands (6.3%), and Jamaica (4.9%). In Caribbean-born women and men with breast cancer, having a first- or second-degree family member with breast cancer was associated with having any BRCA1 or BRCA2 germline variant (odds ratio, 1.58; 95% CI, 1.24-2.01; P < .001). A BRCA1 vs BRCA2 variant was more strongly associated with triple negative breast cancer (odds ratio, 6.33; 95% CI, 2.05-19.54; P = .001).

Conclusions and relevance: In this study, among Caribbean-born individuals with breast and ovarian cancer, 1 in 7 had hereditary breast and ovarian cancer. The proportion of hereditary breast and ovarian cancer varied by island and ranged from 23% in the Bahamas to 4.9% in Jamaica. Each island had a distinctive set of variants.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr George reported receiving grants from Susan G. Komen Foundation, grants from Color Genomics, and grants from National Institutes of Health National Institute on Minority Health and Health Disparities Loan Repayment Program during the conduct of the study. Dr Narod reported receiving grants from Susan G. Komen Foundation during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Distribution of Pathogenic and Likely Pathogenic Variants by Country
See this image and copyright information in PMC

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