A genome analysis of the DNA of Nigerian women uncovered a higher burden of mutations in breast cancer-related genes, which may explain why sub-Saharan African women are more likely to develop aggressive breast cancer at a much younger age than women in the U.S.
These results led to the development of the first African breast cancer risk prediction model to help reduce breast cancer mortality in these women.
African and African-American women are more likely to develop triple-negative breast cancer and to die from it than women of other ancestries.
To identify a potential inherited predisposition to breast cancer in this population, an international team of researchers from the University of Chicago and the University of Ibadan in Nigeria studied 1,136 Nigerian women with invasive breast cancer and 997 age- and heritage-matched women without cancer used as controls, from the same communities.
“This is the first study to use high-throughput genomic analysis of African women,” Olufunmilayo Olopade, MD, director of the Center for Clinical Cancer Genetics, associate dean of the Center for Global Health at the University of Chicago, and the study’s lead author, said in a press release.
The study is part of the Nigerian Breast Cancer Study, based in Ibadan in southwest Nigeria, which has been active for more than 20 years. Data from the study has shown a steady rise in breast cancer incidence in Nigeria.
Out of 577 patients with available information on tumor stage, 86.1% (497 women) were diagnosed at advanced stages of the disease — stage 3 (241 women) and stage 4 (256 women) — a much higher percentage than women in the U.S.
Moreover, almost half of the women (45.9%) were diagnosed with the aggressive triple-negative breast cancer subtype, which is linked to a poorer prognosis regardless of the country where patients are treated. Triple-negative breast tumors lack the receptors for estrogen, progesterone hormones, and the human epidermal growth factor.
The researchers analyzed the genomic sequence of 25 genes linked to a higher risk of breast cancer and pinpointed the mutations, or errors, in each gene sequence.
Results showed that out of the 1,136 breast cancer patients, 167 carried an inherited mutation in one of four breast cancer-related genes, the most common being those in the BRCA1 gene, affecting 7% of patients, and BRCA2, affecting 4%. This was followed by PALB2, in 1%, and TP53, in 0.4%.
Women with mutations in the BRCA1 or TP53 genes developed breast cancer at younger ages than women with mutations in other genes. While the median age of diagnosis in all cases was 47.5 years, BRCA1 carriers were diagnosed at an average age of 42.6 and those with TP53 mutations even earlier, at an average age of 32.8.
“Based on state-of-the-art genomic technologies, two things were clear,” said Mary-Claire King, PhD, a professor of medicine and genome sciences at the University of Washington in Seattle and a co-author of the study. “Risks to Nigerian women who carry mutations in breast cancer genes are higher than risks to women in the U.S. with mutations in the same genes. And inherited breast cancer plays a bigger role in the total occurrence of breast cancer in Nigeria compared to the U.S.”
“Genomic sequencing to identify women at extremely high risk of breast cancer could be a highly innovative approach to tailored risk management and life-saving interventions,” the researchers wrote in the study.
Following these results, the Chicago-Ibadan team went on to develop a breast cancer risk prediction model for women in Nigeria and other sub-Saharan African countries, who are known to develop breast cancer an average of 10 years earlier than women in the U.S.
Their model was described in a separate study, titled “Development of a Breast Cancer Risk Prediction Model for Women in Nigeria,” published in the journal Cancer Epidemiology, Biomarkers & Prevention.
The aim was to identify women at a higher risk for developing breast cancer, so they can be actively surveyed, which may “substantially reduce premature mortality from breast cancer,” the researchers wrote.
They developed their breast cancer risk prediction model by analyzing 1,811 breast cancer cases and 2,225 controls from the Nigerian Breast Cancer Study, from 1998 to 2015.
“Coordinating our team of clinicians and scientists and community elders in Nigeria was no small feat, but we got the job done despite resource constraints,” said Adeyinka Falusi, PhD, professor of hematology and L’Oreal/UNESCO Laureate at the Institute for Advanced Medical Research and Training in the College of Medicine, University of Ibadan.
“As the premier institution in Nigeria, the University of Ibadan remains committed to deploying science and technology to improve the health of Africans on the continent and throughout the diaspora,” she said. “Lessons learned in Nigeria can be transferred back to low resource settings in the U.S. and other countries.”