Why Are African Americans at Higher Risk of Premenopausal Breast Cancer?


African American patients are more likely to be diagnosed with advanced cancer and have higher mortality.

Investigators recently discovered a strong link between a genetic variant in African American women and a greater risk of developing premenopausal breast cancer, according to a study published by NPJ Breast Cancer.

TP53 is commonly mutated and implicated in various cancers. The p35 protein is crucial for tumor suppression; however, genetic mutations in this protein can lead to uncontrolled proliferation and stop cell death. Other naturally occurring variants (polymorphisms) of the p53 gene have also been observed to increase the risk of cancer.

In the new study, the investigators analyzed a rare p53 mutation that occurs almost exclusively in individuals with African ancestry. The authors previously showed that this particular mutation inhibits p53 from inducing cell death in vitro studies and increases cancer risk in mice models.

“Based on our previous studies on the functional effects of this genetic variant on the p53 protein, we sought to verify if it alters cancer risk in human carriers,” said senior study author Maureen Murphy, PhD. “This genetic variant is present exclusively in people of African descent, so our study addresses cancer disparities in African American women, a historically underrepresented group in research studies.”

Although African Americans are traditionally underrepresented in clinical studies, this population is more likely to experience certain cancers, compared with other groups.

The National Institutes of Health has reported that African Americans develop disproportionately higher rates of cancers, compared with other racial and ethnic groups. African American patients are also more likely to be diagnosed with advanced disease and have higher mortality, compared with other groups. Discovering the underlying mechanisms that may predispose this population to cancer can significantly improve care.

Included in the study were 14,000 African American women. The authors failed to find a link between the mutation and overall breast cancer risk in all patients.

However, the investigators discovered that a genetic variant of p53 was strongly linked to increased breast cancer risk among premenopausal African American women.

“Our results show that the risk of developing breast cancer is increased by nearly 70% in premenopausal women who carry this polymorphism,” Dr Murphy said. “Because its frequency is very low in the African American population, larger studies will be needed to confirm our observations.”

The authors noted that determining the impact of p53 genetic variants on cancer risk was difficult due to limited data from the specific population of African American women.

These findings strongly indicate that the p53 polymorphism may be linked to increased breast cancer risk, which could lead to novel treatment options in the future. Additional studies with a larger patient population are needed to confirm their findings, the study concluded.

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