Genes point to prostate cancer risk, diagnosis

Gene variant KLF6 may increase a man's risk of prostate cancer by 50%, according to study from New York's Mount Sinai Medical Center published in Cancer Research (2005; 65:1213-22). Separately, researchers from the Center for Prostate Disease Research, Rockville, MD, have discovered a gene that is one of the most common proto-oncogene overexpressions in prostate cancer cells.

Mount Sinai researchers analyzed differences in the KLF6 gene in 3,411 blood samples from men in registries of three major cancer centers. The blood samples were then grouped by those with prostate cancer and a family history of prostate cancer; those with prostate cancer and no family history of prostate cancer; and those without prostate cancer.

About 17% of the patients with a family history of the disease and 15% of patients with no history carried at least one copy of the KLF6 variant. But only 11% of the controls had a copy.

The variant of the gene produces an altered version of the KLF6 protein. Rather than entering the cell nucleus to suppress cell growth as a KLF6 protein usually does, this altered version remains in the cytoplasm where it increases cell growth and potentially leads to the development of cancer.

"Ultimately we plan to investigate the potential of this gene as a diagnostic tool, an indicator of patients' risk for prostate cancer, and as a potential target for new treatments," said John Martignetti, MD, PhD, of Mount Sinai.

In related news, the ETS-related gene (ERG) is one of the most common proto-oncogenes overly expressed at the early phase of prostate cancer, according to the CPDR study published in the March 7 online edition of Oncogene.

Researchers used laser capture microdissected prostate epithelial cells from malignant and benign prostate tissues and GeneChips to identify the ERG gene. They assessed the cancer association of ERG change in combination with other prostate cancer marker genes. By combining ERG with two other genes--DD3 and AMACR--they found the three-gene panel exhibited cancer association in 98% of prostate cancer patients tested.

Correlations of ERG overexpression features have also been noted for PSA recurrence-free survival of prostate cancer patients after radical prostatectomy.