Friday, September 19, 2014

Hopkins Researchers Contribute to "Molecular Family History" for Prostate Cancer

Two of the biggest risk factors for prostate cancer are family history and ancestry. Men of Northern European and African descent have the highest risk of being diagnosed with cancer and aggressive prostate cancer, while a number of studies demonstrate that Asian men may have a lower risk of prostate cancer. Recent improvements in technology make assessment of a person's genome (or genetic code) more facile and affordable. One such method examines SNP (single nucleotide polymorphisms) as they vary from person-to-person and group-to-group. This is a method of "DNA fingerprinting" used by many forensic investigators. Evaluating SNP over a large population can provide data to locate changes in the genome that put a population at risk of prostate cancer. A number of studies have examined SNP in populations of European descent, African-Americans, Japanese and Latino patients.[1-7]

A recent study, in which researchers from Johns Hopkins participated, combined data from a number of these populations to find common genetic causes of prostate cancer around the world. The study combined data on over 87,000 men and found 23 new genetic variants that increase a man's risk of prostate cancer. These variants are found in "non-coding" portions of the genome – DNA regions that regulate genes rather than actually make proteins in the body. It is believed that these variants in the genome explain 33% of the familial risk of prostate cancer.

William Isaacs, PhD and Alan Partin, MD, PhD
William B. Isaacs, PhD, Professor of Urology and Oncology led the Hopkins initiative with Chairman of the Brady Urological Institute, Alan W. Partin, MD, PhD. Dr. Partin commented, "Inheriting any single one of these genetic variants has only a small effect of prostate cancer risk. However, a subset of men will inherit many of these variants, putting them at substantially increase risk for the disease, from three to six times the population average. Men with these risk levels may benefit from disease screening at earlier ages."

Dr. Isaacs states, 
the identification of prostate cancer-related SNPS could serve as a "molecular family history" to enable better screening guidelines and therapies.

The entire manuscript can be found in the March, 2014 issue of Nature Genetics.[1]

Al Olama, A.A., et al., A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet, 2014. advance online publication.

Quotations from this blog are from the press release, "Large Study Reveals New Genetic Variants that Raise Risk for Prostate Cancer," 
from Johns Hopkins Medicine and Vanessa Wasta.

[1] Eeles, R.A. et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat. Genet. 45, 385–391 (2013).
[2] Eeles, R.A. et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat. Genet. 40, 316–321 (2008).
[3] Gudmundsson, J. et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat. Genet. 41, 1122–1126 (2009).
[4] Schumacher, F.R. et al. Genome-wide association study identifies new prostate cancer susceptibility loci. Hum. Mol. Genet. 20, 3867–3875 (2011).
[5] Thomas, G. et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat. Genet. 40, 310–315 (2008).
[6] Cheng, I. et al. Evaluating genetic risk for prostate cancer among Japanese and Latinos. Cancer Epidemiol. Biomarkers Prev. 21, 2048–2058 (2012).
[7] Haiman, C.A. et al. Characterizing genetic risk at known prostate cancer susceptibility loci in African Americans. PLoS Genet. 7, e1001387 (2011).

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