Cancer Genetics Mutations Disparities
Breast
Black & BRCA is a collaboration between the Basser Center for BRCA and its team of patient advocates, researchers and healthcare professionals to bring tailored resources and support to the Black community. The Basser Center is part of the University of Pennsylvania Health System, a major multi-hospital health system headquartered in Philadelphia, Pennsylvania.
“At a time when Black men and women are more likely than the general population to be diagnosed with cancer at later stages when it is less treatable, Black & BRCA seeks to empower individuals to understand their family health history and take action to prevent cancer from one generation to the next.”
Educational Resources
African American and White Women share same genes that increase the risk of breast cancer
The same genes that increase the risk of breast cancer in U.S. White women also greatly increase breast cancer risk among African American women.
These genes include the BRCA1, BRCA2 and PALB2 genes, each of which is associated with a more than seven-fold risk of breast cancer, as well as four other genes associated with a more moderate increase in risk. Previous studies of women of African ancestry were too small to assess genes other than BRCA1 and BRCA2.
“This means that the multi-gene panels that are currently available to test women diagnosed with breast cancer or women at high risk due to their family history will be useful for African American women,” explains Julie Palmer, ScD, (left) of the Boston University School of Medicine.
Researchers in 2020 sequenced the germline (inherited) DNA from 5,054 African American women with breast cancer and 4,993 age-matched African American women without cancer for mutations in 23 genes linked to a predisposition for cancer. They then estimated the risks of developing breast cancer associated with having a mutation in any of the genes.
- Source: “African American and White Women Share Genes that Increase Breast Cancer Risk” on the Boston University School of Medicine website
- See the full text of the scientific paper “Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women” by Julie R Palmer et al.
Rates of genetic mutations similar between Black and White women diagnosed with breast cancer
In a 2021 study of 3,946 Black women diagnosed with breast cancer and 25,287 White women also diagnosed with the disease, the rates of genetic mutations in genes linked to breast cancer were similar. Among the Black women, 5.65% had a mutation in one of the 12 genes, compared with 5.06% of the White women, a difference that is not statistically different.
The researchers, led by Susan Domchek, MD, (right) of the University of Pennsylvania, concluded that all efforts should be made to ensure equal access to genetic testing to minimize disparities in care and outcomes in women diagnosed with breast cancer.
The study also confirmed that Black women were more likely to be diagnosed with breast cancer at a younger age, more likely to be diagnosed with triple-negative breast cancer, and more likely to be diagnosed with estrogen-receptor-negative breast cancer (which tends to grow faster than hormone receptor-positive cancer).
- Source: “Do Black Women Diagnosed With Breast Cancer Have Higher Rates of Genetic Mutations Than White Women?” by Jamie DePolo on the breastcancer.org website
- See the full text of the scientific paper “Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States” by Susan M. Domchek et al.(righ
Cervical
The same genes that increase the risk of breast cancer in U.S. White women also greatly increase breast cancer risk among African American women.
These genes include the BRCA1, BRCA2 and PALB2 genes, each of which is associated with a more than seven-fold risk of breast cancer, as well as four other genes associated with a more moderate increase in risk. Previous studies of women of African ancestry were too small to assess genes other than BRCA1 and BRCA2.
“This means that the multi-gene panels that are currently available to test women diagnosed with breast cancer or women at high risk due to their family history will be useful for African American women,” explains Julie Palmer, ScD, (left) of the Boston University School of Medicine.
Researchers in 2020 sequenced the germline (inherited) DNA from 5,054 African American women with breast cancer and 4,993 age-matched African American women without cancer for mutations in 23 genes linked to a predisposition for cancer. They then estimated the risks of developing breast cancer associated with having a mutation in any of the genes.
- Source: “African American and White Women Share Genes that Increase Breast Cancer Risk” on the Boston University School of Medicine website
- See the full text of the scientific paper “Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women” by Julie R Palmer et al.
Colorectal
The same genes that increase the risk of breast cancer in U.S. White women also greatly increase breast cancer risk among African American women.
These genes include the BRCA1, BRCA2 and PALB2 genes, each of which is associated with a more than seven-fold risk of breast cancer, as well as four other genes associated with a more moderate increase in risk. Previous studies of women of African ancestry were too small to assess genes other than BRCA1 and BRCA2.
“This means that the multi-gene panels that are currently available to test women diagnosed with breast cancer or women at high risk due to their family history will be useful for African American women,” explains Julie Palmer, ScD, (left) of the Boston University School of Medicine.
Researchers in 2020 sequenced the germline (inherited) DNA from 5,054 African American women with breast cancer and 4,993 age-matched African American women without cancer for mutations in 23 genes linked to a predisposition for cancer. They then estimated the risks of developing breast cancer associated with having a mutation in any of the genes.
- Source: “African American and White Women Share Genes that Increase Breast Cancer Risk” on the Boston University School of Medicine website
- See the full text of the scientific paper “Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women” by Julie R Palmer et al.
Endometrial
We performed a comprehensive review of all published scientific literature up to January 2021 reporting histopathologic, genetic and molecular factors associated with racial disparities in patients with endometrial cancer. The interactions and pathways of molecules reported to have significant differential expression in endometrial cancers from Black and White patients were identified with Ingenuity Pathway Analysis. The majority of studies compared Black and White patients; however, limited data are available for other racial and ethnic groups. Reported differences that could account for the worse survival of Black endometrial cancer patients include more aggressive histopathologies and molecular alterations, including upregulation of molecules driving cell cycle progression, and p53 and HER2/NEU signaling. Several of these molecules are targeted by existing pharmaceuticals. These findings encourage further study and the development of race-specific treatment strategies.
https://www.mdpi.com/2072-6694/13/8/1900/htm
Lung
The same genes that increase the risk of breast cancer in U.S. White women also greatly increase breast cancer risk among African American women.
These genes include the BRCA1, BRCA2 and PALB2 genes, each of which is associated with a more than seven-fold risk of breast cancer, as well as four other genes associated with a more moderate increase in risk. Previous studies of women of African ancestry were too small to assess genes other than BRCA1 and BRCA2.
“This means that the multi-gene panels that are currently available to test women diagnosed with breast cancer or women at high risk due to their family history will be useful for African American women,” explains Julie Palmer, ScD, (left) of the Boston University School of Medicine.
Researchers in 2020 sequenced the germline (inherited) DNA from 5,054 African American women with breast cancer and 4,993 age-matched African American women without cancer for mutations in 23 genes linked to a predisposition for cancer. They then estimated the risks of developing breast cancer associated with having a mutation in any of the genes.
- Source: “African American and White Women Share Genes that Increase Breast Cancer Risk” on the Boston University School of Medicine website
- See the full text of the scientific paper “Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women” by Julie R Palmer et al.
Prostate
Finally, a large study investigating the role of genetic mutations or other alterations in prostate cancer showed that biological differences are unlikely to be a major cause of disparities in patient outcomes seen between black and white men diagnosed with advanced prostate cancer.
The study also showed that black men were less likely to receive comprehensive genomic profiling early in their treatment course (which can point to best treatments), and less likely to receive treatment in clinical trials compared with white men. These differences in the early treatment of prostate cancer may explain the differences in outcomes between African-American and white men.
Brandon A. Mahal, MD
“Ultimately, equitable use of comprehensive genomic profile testing, clinical trial enrollment, and subsequent precision medicine treatment pathways can lead to a major reduction in disparities,” said Brandon A. Mahal, MD, Assistant Professor of Radiation Oncology, University of Miami Sylvester Comprehensive Cancer Center, Florida.
According to Dr. Mahal, the number of men who are diagnosed with, and die from, prostate cancer varies widely by ethnicity or race, and African-American men have the greatest burden of prostate cancer.
“These differences are likely due to the interplay of socioeconomic factors, environmental exposures, and biological or epigenetic phenomenon,” Dr. Mahal said.
“Furthermore, precision oncology studies have underrepresented men of African ancestry, thereby limiting our comprehensive understanding of prostate cancer disparities, which can potentially lead to greater disparities,” he suggested.
The study included nearly 12,000 men with advanced prostate cancer who had comprehensive genetic profiling as part of their treatment plan; of these patients, 12% were black. Dr. Mahal and colleagues investigated the genomic landscape and the treatment patterns, according to ethnicity and racial ancestry.
Analysis of the genetic mutations demonstrated differences across ethnic groups, Dr. Mahal said. Among black men with prostate cancer, the frequency of certain genomic alterations was reduced compared with white men, including TP53, PTEN, and TMPRSS22-ERG mutations.
By contrast, genomic alterations such as MEK, SPOP, CDK12, KMT2D, CCND1, and HGF were more common in African-American men than in white men.
However, the researchers found no significant differences in the actionable genes that can be targeted by current therapies, Dr. Mahal said.
“Men of African and European ancestry showed similar patterns of targetable gene alterations, except for BRAF, which was enriched in individuals with African ancestry,” said Dr. Mahal. He added that a previous small study showed similar results in African-American men with prostate cancer.
Discussing these results, Dr. Black said that genes such as SPOP or TMPRSS22-ERG represented early DNA changes and are not affected by treatment. By contrast, TP53 and TPEN are genetic alterations that are likely to be affected by treatment, and they are less common in black men with prostate cancer than in white men.
“There are some genetic alterations that are not necessarily explained by prior treatment, but with the vast heterogeneity of such a population, and the lack of clinical annotation, it is likely due to other confounders,” Dr. Black said.
These results suggest that the ethnic disparities seen in men with advanced prostate cancer are likely not related to the biological differences in the tumor characteristics between white and black men, Dr. Black said.
Review Front Biosci (Landmark Ed)
. 2017 Jan 1;22(5):772-782. doi: 10.2741/4515.
Racial disparities in prostate cancer: a molecular perspective
Arun Bhardwaj
Abstract
Prostate cancer incidence and mortality rates are remarkably higher in African-American men as compared to their European-Americans counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Although socioeconomic factors could account for such differences up to a certain extent, it is now being increasingly realized that such disparity has a molecular basis. Indeed, several differences, including genetic polymorphism, gene mutations, epigenetic modifications, miRNAs alterations, etc., have been reported in malignant prostate tissues from patients of diverse racial backgrounds. Here, we attempt to provide a molecular perspective on prostate cancer racial disparities by gathering available information on these associated factors and discussing their potential significance in disproportionate incidence and clinical outcomes.
https://pubmed.ncbi.nlm.nih.gov/27814645/
The incidence of prostate cancer among African American men is approximately 60 percent higher than among American men of European ancestry, and their mortality rate is two to three times higher. At the time of prostate cancer diagnosis, African American men typically present with more advanced disease than white men. Some evidence indicates that prostate cancer growth is faster and/or there is an earlier transition from latent to aggressive disease in African American men, which may explain, in part, the observation of more advanced disease at diagnosis. These features suggest that the biology of prostate cancer in African American men and white men may differ in important ways.
In support of this notion, genetic analyses conducted by NCI-funded researchers have identified multiple regions on the long arm of chromosome 8 (at 8q24) that are associated with susceptibility to prostate cancer. The researchers have proposed that genetic variation in these regions may explain up to 50 percent of the higher risk of prostate cancer observed among men of African descent.
Some of the same researchers have identified a second chromosomal region—this one on the long arm of chromosome 17 (at 17q21)—that is associated with increased prostate cancer risk among African American men compared with men of other populations. Approximately 5 percent of African American men carry a rare genetic variant in this region that appears to be associated with higher prostate cancer risk. This genetic variant has been found in less than 1 percent of men of other populations.
Ongoing research is aimed at understanding the functional consequences of these and other genetic variants that influence prostate cancer risk—not only among African American men but in all men. Only then will we have insights that have the potential to be translated into clinical benefit, including effective strategies for early detection and disease prevention.
Additional studies have identified epigenetic differences and differences in gene expression patterns and other molecular characteristics between the prostate tumors of African American men and white men. In one study, researchers found higher levels of a protein called Kaiso, a regulator of gene expression, in the nuclei of prostate cancer cells from African American men than in the nuclei of prostate cancer cells from white men. In the study, higher nuclear levels of Kaiso were associated with aggressive prostate cancer, and the protein was shown to decrease expression of E-cadherin, a tumor suppressor protein that functions as a cell–cell adhesion receptor. Loss of E-cadherin-mediated cell–cell adhesion has been implicated in the transition from noninvasive lesions to invasive, metastatic cancers.
https://www.cancer.gov/research/progress/discovery/biology-cancer-health-disparities (2015)