Breast Cancer and Genetic Factors

Breast cancer is a major health problem in the Western world and the leading cause of death among American women 40-55 years of age.
Although the cause of breast cancer is still unknown, it is clear that genetic factors contribute to an ill defined proportion of breast cancer incidence, estimated to be about 5-10% of all cases, but approximately 25% of cases diagnosed before age 40.

Among women born and raised in the US, Black women have a lower risk of breast cancer than White women, but the survival of Black women is poorer. It has been observed that the age distribution of disease onset as well as tumor histology is different between Black and White patients.

African-American patients have a greater incidence between 30-44 years, and medullary carcinoma is more frequent. Tumors in African-American women are more likely to be poorly differentiated, and estrogen receptor negative, and to exhibit high nuclear atypia, and higher S-phase fraction.

The greater percentage of Black women than White women diagnosed with breast cancer under age 44 suggests a genetic contribution to breast cancer in African-American women. However, very few data are available from this population to evaluate this possibility

In West Africa, the founder population of most African Americans, breast cancer has been considered to be a rare virulent disease of young women. Breast cancer in these young women is almost uniformly fatal partly because of ignorance of the disease, and lack of access to modern medical care.

In a recent review of breast cancer cases from Nigeria published by Dr Adebamaowo, the average age at diagnosis was 43 years; 10-15 years younger than in White women. Pre-menopausal women accounted for 74% of the cases and most significantly, 12% of the cases were in women younger than 30 years of age. Quite at variance with the finding in White women, breast cancer incidence in Africa does not increase with age after menopause.

While this figure may in part reflect the lower average age of the African population, the lower average age of breast cancer incidence in Blacks from all regions in North America suggest there is a strong genetic component to breast cancer susceptibility common to populations of African ancestry. Alternatively, environmental factors important in post-menopausal women may be lacking in this populations.

Only 20% European admixture exists among US Blacks, therefore the predominant genetic influences on breast cancer will be similar in Nigeria and the US. Thus, genetic analysis of breast cancer predisposition in West African populations could potentially reveal components of breast cancer susceptibility common to all Blacks in the African Diaspora. Such components should be more readily detected in West African subjects, as these populations remain relatively more genetically homogenous.

With the identification of BRCA1 and BRCA2 genes, highly penetrant genes that confer increased risk of premenopausal breast cancer, as well as a host of low penetrance genes that modify breast cancer risks, it should now be possible to systematically study the genetics of breast cancer in the African Diaspora .

The African Diaspora consists of populations which share a common genetic background, yet reside in widely varying social settings. Heritable aspects of breast cancer should be detectable in cross-cultural comparisons of Blacks in Africa, the Caribbean and North America. Potential protective factors in the environment could be identified because of the sharp contrasts in environmental exposure. However, such comparisons are extremely complex, requiring an infrastructure (accessible populations, clinical resources and processes) that can support unified assessment of exposure and disease).

We have recently established collaborations within the University of Ibadan to study the genetic and environmental factors which contribute to breast cancer in the African diaspora.

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