Mutation May Raise Prostate-cancer Risk In African Americans

Thestudy, by scientists at 13 research centers, found that mutations in agene known as EphB2 occurred in 15 percent of African-American men witha strong family history of prostate cancer. The mutation was found inonly 5 percent of African-American men with no family or personalhistory of the disease and in less than 2 percent of European-Americanmen with no history of the disease.

Prostate cancer rates areextremely high in African-American men. They develop the disease 60percent more often than do European Americans, and they are almost twoand half times more likely to die of the disease.

Until now, nogene mutations have been identified that contribute to hereditaryprostate cancer and prostate-cancer susceptibility specifically inAfrican-American men.

The findings are published online in the Sept. 9, 2005, issue of the Journal of Medical Genetics.

“Thisis the first gene mutation to be associated with familial prostatecancer in African-American men,” says first author Rick A. Kittles,associate professor of molecular virology, immunology and medicalgenetics and a researcher with the Human Cancer Genetics program at TheOhio State University Comprehensive Cancer Center – Arthur G. JamesCancer Hospital and Richard J. Solove Research Institute.

“Next,we must learn more about how this mutation contributes to cancer, andwe must screen for the mutation in a much larger group ofAfrican-American men with prostate cancer to verify its associationwith the disease.”

Then, says Kittles, a specialist inprostate-cancer genetics in African Americans, “perhaps we can beginusing this mutation to help estimate prostate-cancer risk inAfrican-American men.”

The findings are the first to come out ofthe African-American Hereditary Prostate Cancer (AAHPC) study network,a group of 112 African-American families nationally who havevolunteered to help in research to identify genetic risk factors forprostate cancer. Families in the network have had four or more cases ofprostate cancer in the family.

“This as an exciting extension toour original findings implicating EphB2 as a prostate-cancertumor-suppressor gene,” says principal investigator John D. Carpten, ofthe Translational Genomics Research Institute.

“These data nowsuggest that mutations in this gene might predispose African-Americanmen to prostate cancer in a significant way.”

Other evidencesuggesting that EphB2 could be a prostate-cancer susceptibility geneinclude its location on chromosome 1. The exact function of the gene isunknown.

For this study, the researchers isolated the EphB2 genefrom white blood cells taken from 72 African-American men in the AAHPCwith hereditary prostate cancer and examined them for mutations.

Aftersequencing the gene from each volunteer, the investigators found that11 of the 72 men (15.3 percent) had a mutation designated K1019X. Thesame mutation was found in only 5.2 percent in a control group of 329healthy African-American men and in only 1.7 percent of 231European-American control samples.

The findings indicate that theK1019X mutation is found mainly in African-American men, that it isparticularly prevalent in African-American men with a family history ofprostate cancer, and that it increases the risk of prostate cancer inthese men almost three-fold.

“Given its high frequency inhereditary cases, we believe that this mutation is probably associatedwith hereditary prostate cancer in African-American men,” Kittles says.

Fundingfrom the National Institutes of Health (NIH) Center for Minority Healthand Health Disparities, the National Cancer Institute, the Departmentof Defense, the U.S. Public Health Service and the Commonwealth ofPennsylvania supported this research.

The other centersparticipating in the study were the Fox Chase Cancer Center;Translational Genomics Research Institute; the National Genome Centerat Howard University; The University of Texas MD Anderson CancerCenter; University of California Davis Cancer Center; Midtown UrologySurgical Center, Atlanta, Georgia; Columbia University Medical Center;the University of Illinois at Chicago; Medical College of GeorgiaSchool of Nursing; National Human Genome Research Institute; the NIHCenter for Inherited Disease Research; and the Karmanos CancerInstitute.