Sunday, April 12, 2009

Increase in p53 mutation linked to advanced colorectal cancer in blacks

PHILADELPHIA – Researchers have identified a possible genetic cause for increased risk for a more advanced form of colorectal cancer in blacks that leads to shorter survival, according to data published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Understanding the relationship between molecular defects and differences in colorectal cancer incidence, aggressiveness and clinical outcomes is important in individualizing the treatment and in eliminating racial disparities.

"Several studies have identified a disparity between African-Americans and whites for colorectal cancer. What this study does is pinpoint a possible genetic cause," said Upender Manne, Ph.D., associate professor in the Department of Pathology at the University of Alabama at Birmingham.

For the current study, Manne and colleagues analyzed 137 colorectal adenocarcinomas from African-American patients and 236 colorectal adenocarcinomas from non-Hispanic whites. Researchers assessed these carcinomas for p53 mutations and genotyped for codon 72 polymorphisms.

Overall, whites and African-Americans had a similar rate of p53 mutations. However, the frequency of the Pro72 allele was higher in blacks at 17 percent compared with 7 percent among whites. By contrast, the Arg72 allele frequency was higher in whites at 36 percent than in African-Americans, where the frequency was 19 percent.

representation of a complex between DNA and the protein p53

representation of a complex between DNA and the protein p53
Presence of the Pro72 allele in blacks was associated with a more than two-fold increase in mortality due to colorectal cancer.

"This paper shows that in a subset of patients with the Pro72 allele, and the susceptibility to p53 mutations may be a possible molecular explanation for the racial disparity," said Manne. ###

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 28,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and 80 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants.

The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. The AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention.

The AACR's most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.

Contact: Jeremy Moore Jeremy.moore@aacr.org 267-646-0557 American Association for Cancer Research

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