David Hunter
David Hunter, Vincent L. Gregory Professor in Cancer Prevention in the HSPH Department of Epidemiology, was an author on two of the papers. HPH NOW spoke to Dr. Hunter to get an inside look at what the research means and why men should care.
HPH NOW: Can you fill in our readers about the recent history of prostate cancer research?
Hunter: Last year, a company in Iceland called deCODE Genetics published the identification of two genetic variants related to increased risk for prostate cancer. The variants were on a region of chromosome 8 called 8q24. A second team from Harvard Medical School, the Broad Institute, and University of Southern California independently discovered this region. Both papers specified a single nucleotide polymorphism, or SNP, called rs1447295 as being associated with increased risk of prostate cancer.
HPH NOW: And how do the five new papers fit with the 2006 papers?
Hunter: Two of the new papers, both published in the April 1, 2007 issue of Cancer Research, confirm in larger studies that 8q24 is associated with prostate cancer risk. The lead author on one of these two papers is Fredrick Schumacher, a research fellow in HSPH's Department of Epidemiology. He and I were part of a team of researchers from more than a dozen institutions that conducted the largest nested case-control study so far to confirm the link between 8q24 and prostate cancer.
We found that white men who had two copies of a gene variant at the SNP rs1447295 had an approximately 90 percent higher risk of prostate cancer than men who did not have the variant. Men who had one copy of the variant had a 30 percent higher risk. The team also looked to see if there was a link between SNP rs1447295 and breast cancer risk, and found no association, which is a new finding and confirms the specificity to prostate cancer. [Prostate and breast cancer are both considered "hormonally responsive" cancers, so findings for one are often cross-checked with the other, Hunter explained.]
The other three papers published online in the April 1 issue of Nature Genetics. Two of the papers involved the same teams as the 2006 papers. The Health Professionals Follow-up Study contributed data to the third paper, which involved investigators from the National Cancer Institute (NCI) and the Cancer Genetic Markers of Susceptibility (CGEMS) initiative that I co-direct. We found a novel locus in the 8q24 region, and together, the three papers either identify or confirm seven genetic variations associated with increased prostate cancer risk.
HPH NOW: What did your team specifically find?
Hunter: We found a genetic variation that may be responsible for up to 20 percent of prostate cancer cases in white men in the United States. The variation is at SNP rs6983267.
HPH NOW: Do you need both of these variations to have an increased risk?
Hunter: No. They seem to work independently.
HPH NOW: How is it that all five studies came out at the same time?
Hunter: This field is moving incredibly fast, and all the studies were submitted for publication at about the same time. One of the ways we are leveraging new technologies to speed the pace of discovery is that some studies are providing web-access to their data months prior to publication. In CGEMS for instance, we posted the data in October of last year, and both of the other two groups were able to use it in their analyses. This helps sort out the most reproducible results prior to publication of data so the finished products are more likely to agree.
Prostate cancer cells
HPH NOW: One of the interesting aspects of these studies was that the variations were found in an area of the genome thought to have no function, a so-called junk-gene area. What are the implications of this realization?
Hunter: These genetic variants are not directly in DNA sequences that code for genes. The speculation is that something about them is involved in regulation of distant genes, or in the tendency of this region to be amplified in prostate tumors. An emerging theme in genome-wide associations studies of a number of diseases is that the most robust and highly reproducible findings are not necessarily in the coding regions for genes, demonstrating that we have a lot to learn about how differences in the genetic code influence disease risk.
HPH NOW: What is the big picture in terms of these findings? Should men be more hopeful that one day there may be better treatments for prostate cancer?
Hunter: The hope is that understanding the mechanisms by which inherited risks influence tumor formation will lead to new angles of attack for both prevention and treatment.
HPH NOW: What are your next steps? Do you plan a follow-up study?
Hunter: Absolutely. At CGEMS we are following up these results in collaboration with researchers at HSPH and Brigham and Women's Hospital's Health Professionals Follow-Up Study and the Physicians' Health Study to identify additional risk factor loci.
Copyright, 2007, President and Fellows of Harvard College
