Inherited Gene May Increase Risk For Prostate Cancer By 50%  

02/16/05 -- A single gene variant may increase a man's risk of prostate cancer by 50%, according to a new study led by researchers at Mount Sinai School of Medicine and published this week in Cancer Research.

In 2001, Mount Sinai researchers published a study in Science that showed that a gene, known as KLF6, fails to function properly in at least 50 to 60 percent of all prostate cancers. This was the first single gene shown to be responsible for the majority of cases of this disease, which affects approximately 200,000 men each year.

This finding led to the question as to whether or not mutations in this gene that are present from birth might increase an individuals susceptibility to prostate cancer. John Martignetti, PhD, Assistant Professor of Human Genetics at Mount Sinai and colleagues addressed this question by analyzing differences in the KLF6 gene in 3,411 blood samples from men in registries of three major cancer centers (Johns Hopkins University, the Mayo Clinic and Fred Hutchinson Cancer Research Center). Blood samples were divided into three groups based on the individuals from which they were taken -- those with prostate cancer who had a family history of prostate cancer, those with prostate cancer and no family history of the disease, and those without prostate cancer.

About 17% of the patients with a family history of the disease and 15% of patients with no such history carried at lease one copy a single KLF6 variant, but only 11% of the controls had a copy. The significant difference in prevalence of the variant among three groups indicates that individuals with this particular gene variant face an approximately 50% increased risk for developing prostate cancer.

In the 2001 study, Dr. Martignetti, Scott Friedman, MD, Fishberg Professor of Medicine and Chief of the Division of Liver Diseases, and Goutham Narla, an MD/PhD student at Mount Sinai discovered that KLF6, functions as a tumor suppressor gene. Its role is to restrict cell growth. When KLF6 fails to function properly cell growth goes unchecked and cancer may results. It has since been discovered that KLF6 defects are implicated in a number of other human cancers, including colorectal, lung and liver.

The variant of the gene investigated in the report published this week produces a an altered version of the KLF6 protein. Rather than entering the cell nucleus to suppress cell growth as the KLF6 protein usually does, this altered version remains in the cytoplasm, where it has the opposite effect, thus increasing cell growth and potentially leading to the development of caner.

Prostate cancer is among the most prevalent cancers worldwide and is the second leading cause of male cancer-related death in the United States. Incidence is expected to double among men over age 65 in the next 25 years, according to the authors. "Our findings highlight a completely novel and previously unexplored pathway for the development of prostate cancer," said Dr. Martignetti. "Ultimately we plan to investigate the potential of this gene as a diagnostic tool, an indicator of a patients risk for prostate cancer, and as a potential target for new treatments."

Source: Mount Sinai Hospital / Mount Sinai School of Medicine