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Summer, 2011

Genome-Wide Association Study (GWAS)

One of our research goals for 2010 was to complete a Genome-Wide Association Scan (GWAS) of men with early-onset prostate cancer. DNA samples from nearly 1,000 men were examined using a Human660W-Quad BeadChip (a slide spotted with several different probes, each of which will only recognize and pair up with one specific section of DNA). The beadchip allows us to investigate over 650,000 unique sections of human DNA simultaneously. Of the 650,000 unique markers on the beadchip, approximately 550,000 are single nucleotide polymorphisms (SNPs). A SNP occurring within a gene can lead to a change in the amino acid code that tells our cells which proteins to make. When a variation in an amino acid code alters a protein that plays a critical role in the body, it can interfere with normal development or cause a medical condition. In cases like these, SNPs may be associated with a specific disease.

Importance of GWAS

The base-pair CG in DNA molecule 1 changed to base-pair TA in DNA molecule 2
The base-pair CG in DNA molecule 1 changed to base-pair TA in DNA molecule 2, indicating a SNP.
--illustrated by Marine Tempels
Looking at many SNPs allows us to pinpoint the similarities and differences between the genomes of men with early-onset prostate cancer and those who are unaffected by the disease. It is estimated that the 3 billion base pairs of information contained in the human genome would fill up about 200,000 pages or roughly, 347 copies of the book Crime and Punishment. As you can imagine, sorting through that much information on almost 1,000 people would take a considerable amount of time. A GWAS helps by providing a Cliff's Notes version of the genome. The results of a GWAS do not always lead precisely to the genes responsible for a disease, but they can highlight areas of interest on chromosomes, either in known genes, or in chromosomal regions where we did not even know a gene existed.

Statins and Prostate Cancer

Statins are commonly prescribed medications for lowering cholesterol. Several studies have investigated whether men who use statin medications have a different risk of prostate cancer than those who do not. A few studies found evidence that statin use might lower the risk of high-grade (i.e., Gleason 7, 8, 9, or 10) but not low-grade prostate tumors, but overall the results have not been consistent.

In the 2009 PCGP Newsletter, we asked about statins so we could examine whether the use of statins moderated a man's risk of having a recurrence of prostate cancer after diagnosis and treatment. Our results did not differ from what we would have expected if there was no relation between statin use in the past 10 years and the risk of recurrence. Although there was a slight suggestion that risk of recurrence might be reduced among statin users, the difference was not conclusive.

The findings from this and other studies suggest that further research is needed to understand the effect of statins on prostate cancer.

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Prostate Cancer Genetics Project
1500 E. Medical Center Drive
7436 Cancer Center
Ann Arbor, MI 48109

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Email: pcgp-project@med.umich.edu

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Summer, 2011 Newsletter