Variant of a tumor suppressor gene associated with aggressive prostate cancer

Dec 13 2007

A variant of a tumor suppressor gene may be associated with an increased risk of aggressive prostate cancer, according to a study published online December 11 in the Journal of the National Cancer Institute.

Consistent findings that prostate cancer has a genetic component have led researchers to suspect that there are genetic variants that predispose some men to develop prostate cancer.

Jianfeng Xu, M.D., Ph.D., of Wake Forest University School of Medicine in Winston-Salem, N.C., and colleagues examined whether genetic changes to single DNA base-pairs, known as SNPs (single nucleotide polymorphisms), are associated with aggressive prostate cancer in a population of nearly 1,000 Swedish men with and without the disease. The SNPs that were most strongly associated with aggressive prostate cancer were further tested in two independent groups of men who were treated or screened for prostate cancer at Johns Hopkins Hospital in Baltimore.

Starting with about 60,000 SNPs, the researchers conducted an exploratory analysis that identified seven SNPs associated with aggressive prostate cancer. After further testing in the Johns Hopkins population, the authors confirmed that one SNP located in the DAB2IP gene, which is known to be a tumor suppressor gene, was associated with aggressive prostate cancer among men of European and African American descent.

“Our study is among the first to report the presence of a potentially important prostate cancer aggressiveness locus…However, we cannot rule out the possibility of false-positive association. This report is intended to stimulate the conduct of additional confirmation studies for a gene that has strong initial statistical support and biologic relevance as a tumor suppressor gene,” the authors write.

In an accompanying editorial, Jer-Tsong Hsieh, Ph.D., of the University of Texas Southwestern Medical Center in Dallas and colleagues, who first identified this gene, discuss their studies that suggest the DAB2IP gene plays a role in the progression of prostate cancer.

“Several other findings support the biologic role of this gene in aggressive prostate cancer,” the editorialists write.