(London, September 10) Researchers from the UCL Branch of the global Ludwig Institute for Cancer Research (LICR) have uncovered how a genetic variation present in ethnic groups from around the equator may influence cancer susceptibility. The findings published in Nature Genetics have implications for pharmacogenetics, the study of how inherited variations may affect drug metabolism and response, and present a target for future 'designer' cancer therapies.

The p53 tumor-suppressor protein removes damaged cells by a programmed cell death (apoptosis). When the p53 gene is mutated - as it is in approximately half of all human cancers - damaged cells do not die, but rather continue to grow and divide and eventually form a tumor. The two most common polymorphic forms of p53 are p53Pro72 and p53Arg72 and the distribution varies in different ethnic groups. The two forms differ by just one amino acid in the protein sequence. Several years ago, the LICR team discovered that the ability of p53 to control apoptosis is regulated by the ASPP family of proteins.

In this study, the investigators showed that the ASPP family preferentially regulates the p53Pro72 over p53Arg72 form. These results suggest that ASPP protein levels determine cancer susceptibility in people with the p53Pro72 form, the prevalence of which is linked closely to latitude.

According to Professor Xin Lu, the senior author of the study and Director of the LICR Branch, the occurrence of the p53Pro72 form is highest in ethnic populations from around the equator. "It's really interesting to speculate whether the increased exposure to DNA-damaging ultraviolet radiation has resulted in the need for a second level of p53-regulation. The results are important for furthering our understanding of how p53, the tumor suppressor, is regulated, and also offers intriguing hints about how these regulatory mechanisms might have evolved."

While speculations about how the mechanism evolv
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Contact: Sarah L. White, Ph.D.
swhite@licr.org
917-974-7952
Ludwig Institute for Cancer Research
10-Sep-2006