TP53 Gene Variant S47 May Contribute to Increased Cancer Risk in People of African Descent
For years, clinical data have shown that African Americans have a higher death rate and shorter period of survival among patients with commonly diagnosed cancers. While studies have focused on whether socioeconomic factors contribute to these statistics, researchers have been diligently trying to determine a genetic basis for these disparities.
Now, new research from The Wistar Institute has pinpointed a single gene variant that is found only in Africans and African Americans, which makes cancer resistant to cell death and may contribute to increased cancer risk. Study results were published by Jennis et al in Genes and Development.
“We may finally have a truly genetic explanation for why African Americans are more prone to a variety of cancers,” said Maureen Murphy, PhD, Professor and Program Leader in the Molecular and Cellular Oncogenesis Program at The Wistar Institute. “This is a variant that has never been observed in Caucasian populations, so identifying people who have this variant may be crucial for providing improved prognosis and personalized treatment that will lead to better outcomes.”
Study Findings
Dr. Murphy and her colleagues studied the S47 variant of TP53, a tumor-suppressor gene that is mutated and activated in the vast majority of cancers. This particular variant is restricted to people of African descent, occurring in approximately 2% of African Americans and up to 8% of Africans. The Murphy laboratory created a mouse model containing the S47 variant to study its impact in otherwise genetically identical organisms.
While they were not surprised to find that the p53 protein produced by this form of TP53 is impaired in the performance of some functions, the researchers were surprised to find that spontaneous cancer occurred in 80% of the mice with the variant. Liver cancer, lymphoma, and colorectal cancer occurred most frequently in the mice with the S47 variant. Liver cancer is more common in African Americans, and colorectal cancer is responsible for approximately 9% of all newly diagnosed cases of any type of cancer in African Americans.
“Validation of these results in humans will require a large population to determine the significance it has on cancer risk among those of African descent,” Dr. Murphy said. “However, we now have some of the strongest evidence ever obtained for a genetic basis for this disparity, and a larger, population-based study is warranted.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
