Tumor Suppressor Variant May Be Cause of Increased Cancer Risk in African Americans

Clinical outcomes over the years have led cancer researchers to the supposition that African Americans have a higher death rate and shorter period of survival among patients with commonly diagnosed cancers. The underlying cause of these scenarios has produced some hypotheses—many focused on whether socioeconomic factors contribute to the increased mortality statistics. Furthermore, scientists have been searching for a genetic basis for these disparities, with the hope of uncovering therapeutic interventions that could address this seemingly ethnic bias.

Now, investigators at The Wistar Institute have pinpointed a single variant in a gene that is only found among Africans and African Americans that makes cancer resistant to cell death and may contribute to the increased cancer risk.

The findings from this study were published recently in Genes and Development through an article entitled “An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model.”

“We may finally have a truly genetic explanation for why African Americans are more prone to a variety of cancers,” explained senior study author Maureen Murphy, Ph.D., 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.”

Dr. Murphy and her colleagues studied variants of p53, a tumor suppressor gene that is mutated in the vast majority of cancers. One particular variant, S47, is restricted to people of African descent, occurring in approximately 2% of African Americans and up to 8% of Africans.

The Wistar scientists created a mouse model that contained the S47 variant, in order to study the impact of this mutation in otherwise genetically identical organisms. The researchers seek to make this physiologically relevant model system widely available to scientists investigating new treatments for patients with the S47 genetic variant—with the overall goal of developing new diagnostic and efficacious treatment regimens.

“We show that mice expressing S47 in homozygous or heterozygous form are susceptible to spontaneous cancers of diverse histological types,” the authors wrote. “Our data suggest that the S47 variant may contribute to increased cancer risk in individuals of African descent, and our findings highlight the need to assess the contribution of this variant to cancer risk in these populations.”

Surprisingly, the Wistar team also found 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. These findings are in agreement with clinical data that shows liver cancer is more common in African Americans, as well as the fact that colorectal cancer is responsible for approximately 9% of all newly diagnosed cases of cancer among 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 noted. “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.”