Vanderbilt researchers have identified haplotypes, ancestral fragments of DNA, that are associated with hereditary prostate cancer (HPC) in a first-of-its-kind genomic study made possible by the study of prostate cancer patients with family histories of the disease.
The study, published March 23 in Nature Communications, explains roughly 9 percent of prostate cancer heritability. One mutation increased risk as much as 22-fold. Another mutation increased risk 4-fold, and was observed even among men without a strong family history. The researchers identified 183 variants associated with HPC at genome-wide significance, including these and others that had not been previously reported.
“We’ve taken a comprehensive shotgun approach to investigate data at this (chromosome) location and have been able to deconstruct how it contributes to risk, including which of the haplotypes impact age of onset and also aggressiveness,” said the study’s senior author, Dr. Jeffrey Smith, associate professor of medicine.
The study is believed to be the first to identify haplotypes comprehensively from all associated genetic variants at a locus. The study introduces new methods for finding genetic variants most contributing to risk.
The study’s lead author is Dr. William Dupont, professor of biostatistics and preventive Medicine. Other contributors include urologists Dr. Sam Chang, the Patricia and Rodes Hart Professor of Urologic Surgery; Dr. Joseph Smith, the William L. Bray Professor of Urology, and Dr. Michael Cookson.Tags: Friday Letter Submission, Publish on April 03