Variant in Gene May Increase Cancer Risk in Those With Common TP53 R337H Mutations

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Scientists studying a common TP53 R337H variant found among people of Brazilian descent discovered that a variant in the tumor-suppressor gene XAF1 increases cancer risk when combined with the inherited TP53 R337H mutation. These findings were published by Pinto et al in Science Advances.

“We expect these results to have a significant impact on public health,” said corresponding study author Emilia Pinto, PhD, of the Department of Pathology at St. Jude Children’s Research Hospital, in a statement. “Once clinicians know what variants to look for, they will know how to better manage those patients with higher cancer risk.”

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Identifying TP53 R337H

More than 20 years ago, St. Jude researchers first identified the TP53 R337H inherited variant among Brazilian people. Dr. Pinto and her colleagues later identified TP53 R337H as a founder mutation—one introduced to Brazil during its colonization. While rare in the general population, TP53 R337H is common in Brazil. It is found in 1 out of every 300 Brazilians.

“The TP53 R337H mutation does not explain the entirety of cancer risk,” said senior study author Gerard Zambetti, PhD, also of the Department of Pathology. “Variation among individuals with TP53 R337H can lead some to develop several forms of cancer—some … develop a single cancer and others … never develop cancer at all.”


From their whole-genome sequencing study, the researchers identified a variant in the tumor-suppressor gene XAF1 in a subset of TP53 R337H mutation carriers. Individuals who have inherited both the XAF1 variant and the TP53 R337H mutation are at a greater risk of cancer than those who have only the TP53 R337H mutation.

TP53 mutations are prevalent in individuals with rare pediatric adrenocortical carcinoma. However, TP53 mutations are a prominent factor in many other types of cancer. The knowledge that XAF1 modifies TP53 may fuel further research into whether this target can become the basis of novel treatment strategies.

St. Jude Global

St. Jude researchers studied the causes of this variation through whole-genome sequencing of individuals of Brazilian ancestry. The partnerships forged through St. Jude Global were key to obtaining the samples necessary to do this work.

Led by the Department of Global Pediatric Medicine, St. Jude Global has formed the St. Jude Global Alliance, which includes programs in the Asia-Pacific region, Central and South America, China, the East and Mediterranean, Eurasia, Mexico, and sub-Saharan Africa.

“This study would not have been possible without the collaboration of our partners around the world,” said study author Carlos Rodriguez-Galindo, MD, Chair of the St. Jude Department of Global Pediatric Medicine. “These results will have an impact on public health in Brazil but are also important for the pediatric cancer community at large.”

Disclosure: The research was funded in part by the National Institutes of Health, the Speer Charitable Trust, the EXPOGEN-CANCER CNRS International Associated Laboratory, and ALSAC. For full disclosures of the study authors, visit

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®.