Cancer is an increasing global public health burden. This is especially the case in sub-Saharan Africa (SSA); high rates of cancer—particularly of the prostate, breast, and cervix—characterize cancer in most countries in SSA. The number of these cancers in SSA is predicted to more than double in the next 20 years (1). Both the explanations for these increasing rates and the solutions to address this cancer epidemic require SSA-specific data and approaches. The histopathologic and demographic features of these tumors differ from those in high-income countries (HICs). Basic knowledge of the epidemiology, clinical features, and molecular characteristics of cancers in SSA is needed to build prevention and treatment tools that will address the future cancer burden. The distinct distribution and determinants of cancer in SSA provide an opportunity to generate knowledge about cancer risk factors, genomics, and opportunities for prevention and treatment globally, not only in Africa.
The most frequent cancers in African countries include prostate, lung, liver, leukemia, non-Hodgkin’s lymphoma, and Kaposi’s sarcoma in men and breast and cervical cancer in women (see the figure). Distinct risk factors in SSA contribute to the understanding of cancer etiology in ways that may not be as easily studied in HICs. For example, the observation of high rates of Burkitt’s lymphoma in SSA launched the research that identified Epstein-Barr virus as the causal agent of Burkitt’s lymphoma (2), thus providing some of the earliest knowledge about the infectious and molecular etiology of cancer. Similarly, the high prevalence of HIV infection and the attendant large number of HIV-associated cancers in SSA have enabled research that has led to understanding of the causes and treatment of cancers exacerbated by HIV infection, including cervical cancer, Kaposi’s sarcoma, and non-Hodgkin’s lymphoma (3).
Patients with cancer in SSA are often diagnosed when their disease is in advanced stages. This is in part a consequence of inadequate resources for cancer prevention and early detection. Delayed diagnosis coupled with inadequate treatment options is a major reason for the continent’s cancer mortality rates, which are 1.5- to 4-fold higher than in HICs for leading cancers (1). Studies that focus on features of late-stage and aggressive disease will be required to better understand how to manage such disease states. This research is required to develop and implement early detection and treatment modalities that can be implemented in low-resource settings such as SSA, where availability of laboratory or imaging technologies is limited.
Although molecular and other biological data that address cancer etiology and progression in SSA are limited, emerging evidence suggests that distinct tumor histopathology, tumor subtypes, and molecular signatures exist in SSA. For example, Nigerian breast cancer cases were defined by increased mutational signature associated with deficiency of the homologous recombination DNA repair pathway, pervasive mutations in the tumor suppressor gene TP53, mutations in GATA binding protein 3 (GATA3), and greater genomic mutational burden (indicating aggressive biology), compared with breast tumors from African Americans or Caucasians (4). This suggests different tumor etiologies by race or geography, perhaps reflecting particular environmental exposures to carcinogens, and may provide knowledge about the spectrum of breast cancer molecular phenotypes that may be composed of distinct molecular subtypes and represent different frequencies of known subtypes in non-Africans. Knowledge of these differences can lead to optimized monitoring and treatment across all populations.
Early age at diagnosis is a hallmark of cancer in SSA, which has been proposed to reflect a higher rate of hereditary cancer in SSA. This is supported by the observation that although 29% of SSA women and 33% of Caucasian women are between ages 25 and 49, 58% of SSA women are diagnosed with breast cancer before they are 50 years old, compared with 21% of Caucasian women (5). Breast tumors in SSA Black cases are twice as likely as SSA Caucasian cases to be the triplenegative subtype, meaning that the estrogen, progesterone, and HER2 receptors are not expressed by the breast cancer cells, making them highly aggressive and difficult to treat (6). These molecular features are hallmarks of hereditary cancers; genetic testing for pathogenic sequence variants in the tumor suppressor genes breast cancer 1 (BRCA1) and BRCA2 in a series of Nigerian breast cancer cases suggested that the rate of cancers in women with BRCA1 or BRCA2 germline pathogenic sequence variants is higher than in Caucasian populations (7). Although large population studies of hereditary cancer in SSA do not yet exist, BRCA1 and BRCA2 mutations of SSA origin are also found in African Americans, and the type of mutations in BRCA1 and BRCA2 differs between SSA and non-SSA populations (8).
Generation of knowledge about cancer in SSA will lead to both improved cancer prevention and treatment. Protocols and networks are being formed to study cancer in SSA patients and translate this knowledge to health care in SSA (9). These protocols may begin with those used in HICs but must be optimized to low-resource settings, which have limited access to equipment, trained personnel, and therapies. Although the availability of basic research infrastructure is more limited in SSA than in HICs, there are numerous basic science and translational research institutes in SSA, including those that can address cancer genomics and molecular biology. Pan-African initiatives, such as the Human Heredity and Health in Africa (H3Africa) initiative, have developed common protocols, data systems, and collaborative networks that are developing the infrastructure and resources required to address cancer needs in SSA. Africa-based organizations that foster cancer research, translation, infrastructure, and training also exist, including the African Academy of Sciences and the African Organization for Research and Training in Cancer. The World Economic Forum has initiated a “Leapfrogging with Precision Medicine” initiative that will advance the use of genetics and genomics in cancer prevention and treatment. These and many other institutions and activities have the potential to develop the knowledge and sustainable resources needed to address the cancer burden in SSA.
In addition to benefiting the treatment of cancer patients in SSA, the knowledge gained from research on the continent will be informative for cancer globally. Evidence suggests that diversity in study populations will improve the ability to generate and generalize knowledge that can be applied to cancer and other diseases. For example, rare mutations judged to be pathogenic on the basis of Caucasian mutation frequency data were later found to occur commonly in African American populations (10). Knowledge of mutation frequency subsequently led to the opposite conclusion that these variants were nonpathogenic. This misclassification of pathogenicity led to molecular misdiagnoses that could have been avoided had diverse populations been included in the original study cohort. Similarly, it has been observed that use of artificial intelligence and other “big data” approaches in diagnostic and therapeutic applications will be suboptimal if these approaches are trained and validated in nondiverse populations.
A limited scope of population data may perpetuate or exacerbate existing biases in the information needed to generate effective clinical and public health interventions (11). Thus, it is not only the underrepresented population that will benefit from increased research representation but all populations. There is growing evidence that genetic risk prediction models developed in Caucasian populations may not be appropriate in African-descent populations. These results suggest that ancestry-specific models may be required to optimally predict cancer risk. Such models may use genetic variants defined from the discovery of relevant race-specific disease-associated variants and/or use ancestry-specific genomic markers to define ancestry rather than self-identified race or ethnicity.
Because of the underlying genetic and genomic relationships between Africans and members of the African diaspora (primarily in North America and Europe), knowledge gained from research in SSA can be used to address health disparities that are prevalent in members of the African diaspora. West African genomic ancestry (the ancestral origin of most African Americans) has been reported to confer the highest genomic risk for prostate cancer of any population worldwide (12). Selection against a prostate cancer susceptibility locus on chromosome 2q37 has led to lower frequencies of this risk allele in Caucasians and higher frequencies in Africans and African Americans (12). KhoeSan (an indigenous southern African people) ethnicity has also been associated with prostate cancer risk (13). These data from African populations may help elucidate the causes of cancer disparities, particularly in African Americans.
Diagnostic, monitoring, and treatment technologies developed out of necessity in low-resource settings provide an opportunity for cost-efficient and accessible technologies that can be implemented in HICs. In particular, development of point-of-care technologies that provide rapid and accurate cancer diagnosis or treatment in SSA could be applied in community settings to address disparities in access to cancer services in HICs. When technologies, including data-derived models of risk or prognosis, are not developed so that they can be applied in diverse settings and populations, health disparities can be created or increased (14). Development of technologies that can be used in SSA could provide knowledge about optimal implementation of these technologies worldwide. Advances in science and technology and the concomitant increase in capacity for health improvements will increase diversity as a means to remove bias from cancer genomics studies and improve the quality of cancer prevention and treatment globally.
Acknowledgments: The author is supported by National Institutes of Health grant U01-CA184734.