Key genomic differences in breast cancers of women of different ethnicity
Study of genomic data from breast cancers of Nigerian women, compared with American women, highlights significant differences that may help targeted treatment for the epidemic across Sub-Saharan Africa.
A study comparing DNA and RNA data from Nigerian breast cancer patients to patients in a United States database found that certain aggressive molecular features were far more prevalent in tumours from Nigerian women than in black or white American women.
The study’s authors say those differences in a number of molecular features could at least partially explain disparities in breast cancer mortality for women from Nigeria, and perhaps other West African nations.
Commenting on the potential gains of their study, author Olufunmilayo Olopade, MD, the Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics, associate dean for Global Health and director of the Center for Clinical Cancer Genetics at the University of Chicago Medicine, said: “In the era of precision medicine our data provide insights that could reduce the number of deaths from breast cancer across Sub-Saharan Africa and the developing world”.
“Without data, we make wrong policies,” Olopade added. “Understanding the molecular mechanisms that trigger lethal breast cancers is the most fundamental question remaining in breast cancer research, and is a crucial first step toward intervention.”
The study, “Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features,” compares genomic data from 1,037 U.S. patients, provided by The Cancer Genome Atlas (TCGA), to genomic data from 194 Nigerian women with breast cancer. The researchers found multiple, often unexpected, genetic differences between the racial and ethnic groups.
Although the Nigerian patients in the study were much younger, on average, they had more advanced disease at the time of diagnosis and higher mortality rates than women from the TCGA group, most of whom were of European heritage.
Breast cancer rates are increasing in Nigeria and across Sub-Saharan Africa at an alarming pace without the necessary infrastructure to stem the epidemic.
In a transnational collaboration to establish a platform for translational breast cancer research in Africa, researchers from the University of Chicago, Novartis Biomedical Research Institute, University of Ibadan and Lagos State University identified 25 different genes from Nigerian patients that were significantly mutated, but potentially treatable with novel therapies in clinical trials.
Aggressive features found in these women include the inability to repair damaged DNA – a mutational process known as homologous recombination deficiency, for which there are emerging therapies. These include drugs in development that target the immune system.
One of the most frequently mutated genes was the tumour-suppressor gene TP53. 62% of the African women in the study had TP53 alterations, compared to 46% of African-Americans with breast cancer and 29% of the TCGA group, primarily U.S. women of European ancestry. The second most frequently mutated gene is human epidermal growth factor receptor 2 (HER2), for which there are highly effective therapies.
“Nigerian women,” Olopade said, “should be provided access to HER2 targeted therapies.”
Overall, younger Nigerian patients had more mutations in TP53 and in GATA3, which is associated with oestrogen receptors, than black patients from the TCGA. White TCGA patients had fewer mutations than black TCGA patients.
They also found significant cancer-related mutations in three genes that had not been previously associated with breast cancer: PLK2, KDM6A and B2M. (A fourth gene was identified after the current study was under review.) PLK2 is a presumed tumour suppressor. KDM6A is frequently mutated in other cancers, and B2M inactivation has been associated with lung cancer.
Tumours from Nigerian women were frequently characterised by “molecular features of aggressive disease,” said co-senior author Jordi Barretina, PhD, formerly at the Novartis Institutes for Biomedical Research in Massachusetts, and now the Director of the Girona Biomedical Research Institute in Spain. “The most prominent was the prevalence of homologous recombination deficiency among women with oestrogen-receptor positive disease.”
The study, according to the authors, “lays the foundation for a more concerted effort to reduce disparities in cancer outcomes by first closing the knowledge gaps. Nigerian women,” they add, “could benefit from increased access to genomically-tailored treatments.”
The study was published in Nature Communications.