New Regions in DNA Statistically Associated with Prostate Cancer

Dr. Catalona and his research collaborators have just completed a linkage analysis of DNA obtained from blood samples collected over ten years from brothers with prostate cancer.

A linkage analysis is a statistical method to determine if two kinds of observations or results occur together more often than one would expect by chance alone.

For example, if all brothers with prostate cancer have a certain type of gene on chromosome 16 and brothers without prostate cancer do not share it, then the gene probably caused the prostate cancer. In addition to providing for the development of new blood tests to identify individuals who are genetically predisposed to prostate cancer, further research in this area may also provide important insights into preventing prostate cancer and developing new and more effective treatments for the disease.

The linkage analysis for this particular research project focused on pairs of brothers who have the same genetic markers in certain regions more often than would be expected by chance alone.

The researchers discovered five new regions statistically associated with prostate cancer. This discovery means that some fraction of men may carry a mutated gene that predisposes them to prostate cancer.

Previous reports have shown that certain genes in some of these regions are commonly not present. These “missing” genes are called tumor suppressor genes. They normally regulate cell growth.

They are like the brakes of a car. When they are deleted, the car runs out of control. Other genes are like the accelerator of the car and when they are turned on too much, the car goes out of control.

The study involved 230 sets of brothers (188 pairs, 40 trios, and 2 quartets) for a total of 504 men tested. In total, the analysis involved performing approximately 209,000 genotypes (DNA tests for variations of genetic markers which are selected at evenly spaced distances along the length of the human chromosomes).

The researchers divided the brothers into groups according to whether or not they had a strong family history of prostate cancer, an early or late age onset of the disease, or had a family history of breast cancer.

These subanalyses discovered seven new regions in the DNA that were associated with family history of prostate cancer, age at diagnosis, and regions that may cause prostate cancer in men and breast cancer in women.

A genetic connection does exist between prostate and breast cancer. There are genes that when mutated in men cause prostate cancer and when mutated in women cause breast cancer.

Thus a mother can pass prostate cancer on to a son and a father can pass breast cancer to a daughter.

Future studies are being directed at narrowing down these regions to clone the specific genes involved. Then, studies will be performed to determine how these genes function normally and how they cause cancer when they are mutated.

Other doctors participating in this project include Brian Suarez at Washington University; James Burmester, James Weber, and Karl Broman at the Marshfield Research Foundation; and John Witte and Robert Elston at Case Western Reserve University.