PHILADELPHIA — (Feb. 27, 2017) — Scientists at The Wistar Institute in collaboration with Roswell Park Cancer Institute found a significant association between a rare genetic variant of the p53 gene present in African American women and their risk of developing breast cancer in premenopausal age. The study was published online by the journal NPJ Breast Cancer.
TP53 is the most frequently mutated gene in human cancer. The p53 protein is a critical tumor suppressor in the cell and genetic mutations that occur in cancer cause a loss of its function in regulating proliferation arrest and cell death. In addition to these changes, there are several minor, naturally occurring genetic variants of the p53 gene, also known as polymorphisms, and some of them are associated with an increased risk of cancer.
The rare p53 polymorphism analyzed in this study is found almost exclusively in populations of African descent. Wistar scientists have previously shown that this polymorphism impairs the ability of p53 to induce cell death in vitro and significantly increases cancer risk when recreated in a mouse model. The new study analyzed the statistical association of this variant with the risk of developing breast cancer in African American women.
"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 Maureen Murphy, Ph.D., professor and program leader of the Molecular and Cellular Oncogenesis Program at Wistar and senior author of the study. "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."
"Our results show that the risk of developing breast cancer is increased by nearly 70 percent in premenopausal women who carry this polymorphism," Murphy said. "Because its frequency is very low in the African American population, larger studies will be needed to confirm our observations."
Murphy and colleagues conducted statistical studies on a cohort of more than 14,000 women of African descent and didn't find any association of the polymorphism with increased breast cancer risk overall. However, as previously observed with other genetic variants of p53, a significant association was present in women in premenopausal age.
Elucidating the effects of p53 polymorphisms on cancer risk is a challenging task, especially due to the limited availability of sample cohorts from specific populations. This study provides a strong suggestion that the genetic variant considered might be associated with a significant increase in breast cancer risk, although this association will need to be confirmed in a larger sample set.
This work was supported by National Institutes of Health grants R01 CA102184, CA201430, P01 CA151135, R01 CA092447, R01 CA135288, P01 CA82707, R25-CA57726, NICHD-N01-HD-3-3175, NCO-N01-PC-67010, NIEHS-ES07084, R01 CA142996, P50 CA125183, R01 CA89085, and U01 CA161032; National Cancer Institute grant UM1CA164974 and the Intramural Research Program of the National Cancer Institute, Center for Cancer Research; grants from the Breast Cancer Research Foundation, the University Cancer Research Fund of North Carolina, the Department of Defense Breast Cancer Research Program, the Era of Hope Scholar Award Program W81XWH-08-1-0383, the Komen Foundation for the Cure, and the Stacy Goldstein Faculty Scholar Award. Core support for The Wistar Institute and the Rutgers Cancer Institute of New Jersey was provided by the Cancer Center Support Grants P30CA010815 and P30CA072720, respectively.
Qin Liu is a co-author of this study from The Wistar Institute. Other co-authors include: Song Liu, Chi-Chen Hong, Qiang Hu and Christine B. Ambrosone from Roswell Park Cancer Institute; Dezheng Huo and Olufunmilayo I. Olopade from the University of Chicago; Sonia C. Dolfi and Kim M. Hirshfield from Rutgers Cancer Institute of New Jersey; Andrew F. Olshan and Sarah Nyante from University of North Carolina; Temidayo O. Ogundiran from University of Ibadan, Nigeria; Clement Adebamowo from University of Maryland; Susan M. Domchek and Katherine L. Nathanson from the University of Pennsylvania; Barbara Nemesure from Stony Brook University; Stefan Ambs and Regina G. Ziegler from National Cancer Institute; William J. Blot, Wei Zheng and Sandra L. Deming from Vanderbilt University; Ye Feng, Sue A. Ingles, Michael F. Press and Christopher A. Haiman from University of Southern California; Esther M. John from Stanford University; Leslie Bernstein from Beckman Research Institute; Jennifer J. Hu and Jorge L. Rodriguez-Gil from University of Miami; Kathryn L. Lunetta and Julie R. Palmer from Boston University.
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.
Story Source: Materials provided by Scienmag