A new gene-sequencing study, led by a team at Sylvester Comprehensive Cancer Center in collaboration with clinicians and researchers from various Caribbean countries, is getting attention at a national cancer conference.
For its annual meeting in April, the American Association for Cancer Research (ACCR) tapped Sylvester researcher Sophia George, Ph.D., to present findings published March 1 in JAMA Network Open. Titled “Gene Sequencing for Pathogenic Mutations Among Adults with Breast and Ovarian Cancer in the Caribbean,” it is the largest cross-sectional study of its kind. Dr. George was also part of a panel discussion.
The National Cancer Institute (NCI) Center to Reduce Cancer Health Disparities highlighted Dr. George’s presentation on social media.
“It’s exciting that women’s cancer health disparities are at the forefront of this year’s AACR conference. This is in alignment with the NCI’s mission of working toward health equity and justice,” Dr. George said.
Judith Hurley, M.D., an oncologist and researcher at the University of Miami Miller School of Medicine, has been studying racial disparities in breast cancer rates since 2002. After Dr. Hurley noticed that many of her Bahamian breast cancer patients were unusually young, she asked colleagues about this anomaly. They, too, had observed that their own Bahamian patients were pre-menopausal.
“We asked ourselves, ‘Why is this happening? What’s going on?’” Dr. Hurley recalled.
Intrigued, she and Dr. George joined forces with other researchers from Sylvester, the University of Toronto, and the Bahamas to tease out the reason. They found that more than a quarter of the women they studied had mutations in two genes, BRCA1 and BRCA2. (By comparison, these mutations make up less than 5% of U.S. breast cancer cases.) Researchers also determined that the average age of breast cancer onset in Bahamian women was 42 — about 20 years younger than for American women.
The Sylvester team expanded their research to six other English and Creole-speaking Caribbean islands, teaming up with colleagues in the Cayman Islands, Haiti, Dominica, Barbados, Jamaica, and Trinidad and Tobago.
The study sheds light on the differences — and commonalities — among the islands, information that they hope will lead to better screening and treatment of Caribbean cancer patients both in their homelands and in South Florida. Breast cancer is the leading cause of death in Caribbean women, while ovarian cancer ranks as the fourth.
Dr. Hurley pointed out that at least 10% of the Black population in the U.S. is comprised of Caribbean-Americans, with pockets of high concentration in certain metro areas, including South Florida. (A 2015 Pew Research Center study found that 34% of the black population in Miami were immigrants.)
‘You bring your genes with you’
“Their health problems are our health problems,” Dr. Hurley explained. “When you move to a new country, you bring your genes with you.” She noted that half of Miami’s Black breast cancer patients hail from the Caribbean.
Drs. Hurley and George’s study found that the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%) with Jamaica ranking as the lowest (4.9%). Barbados came in second in the percentage of hereditary cancer at almost 18%, followed by Trinidad & Tobago (12%), Dominica (8.8%), Haiti (6.7%), and Cayman Islands (6.3%).
All in all, one in seven of Caribbean-born individuals diagnosed with breast and ovarian cancer had at least one inherited mutation. The mean age of patients with mutations was also younger, 40.7, compared to the 47.5 of patients without mutations.
Perhaps the most fascinating finding was the diversity of mutations among each of the island nations. Dr. George, who focuses her research on molecular genetics and epigenetics, said some might assume that women of African descent would have the same mutations.
“But we found that it was different from island to island,” she said. “Each country had its own spectrum of mutations. Each country had its own unique genetic fingerprint.”
This variety can be attributed to the long history of both forced and voluntary immigration to the islands. While the populations are predominately of African descent, a sizable percentage can also trace their ancestry to European, Indigenous, Asian, Indian, and Middle Eastern immigrants.
For instance, cancer patients in Trinidad, home to many descendants of indentured servants from what is now India and Pakistan, tested for the BRCA1 and BRCA2 but also for PALB2, RAD 51C, and CHEK2 mutations. BRCA1 and BRCA 2 dominated in the Bahamas.
‘A racial and ethnic salad’
“The Caribbean has always been more of a racial and ethnic salad, much more diverse than the continental U.S.,” Dr. Hurley said.
For their study, Drs. Hurley and George conducted germline genetic tests in 1,018 adult women and men with breast and ovarian cancer. Of these, 996 participants were women. Twenty-one had ovarian cancer. Initially, researchers screened only for the BRCA1, BRCA2, PALB2 and RAD51 mutations. However, toward the end of the study as multi-gene panel testing became available, study participants underwent a full next-generation sequencing on a panel of 30 genes.
Such granular detail provides valuable information that can lead to better preventive measures as well as improved use of targeted therapies, Dr. George said. Testing Afro-Caribbean women for only BRCA1 and BRCA2, for example, would miss other mutations that are common in this population.
The Sylvester researchers’ work has already changed the guidelines for breast cancer screenings in the Bahamas. While the American Cancer Society recommends screenings to start when women hit their 40s, Bahamian women with a first-degree breast cancer relative are advised to begin ultrasounds in their mid-twenties.
Drs. Hurley and George plan to continue studying inherited breast and ovarian cancers in U.S. immigrant and non-immigrant populations of African descent. They’ve noted that the type of breast cancer women from Haiti develop in the U.S. is different than the one their counterparts develop in Haiti. What’s more, Afro-Caribbean breast cancer patients in South Florida have a better survival rate when compared to local African-Americans.
They’re particularly interested in looking at these groups’ epigenetics factors.
“Inherited mutations (which are called germline mutations) are hundreds or even thousands of years old,” Dr. Hurley explained. “But the epigenetic changes can be seen in days, weeks or months. This interaction between the DNA that you inherited from your parents and the epigenetic changes in your DNA that are caused by fertility factors, environmental exposures, your diet and lifestyle are fascinating.”