Newly identified gene variants associated with prostate cancer risk

Q&A with Co-author David Hunter of Harvard School of Public Health on Genome Scans and Pitfalls of Personal Profiling

For Immediate Release: Sunday, February 10, 2008

Boston, MA – Three studies were published today on the advance online site of Nature Genetics in which at least 10 newly identified genetic variants are associated with increased susceptibility to prostate cancer. The findings double the number of known variants associated with risk of the disease and result from genomewide association studies.

To better understand these new findings, Harvard School of Public Health (HSPH) has conducted a Q&A with Professor David Hunter, a co-author of one of the papers. He addresses questions about prostate cancer, the growing field of genome scans, and the potential pitfalls of personal genome profiling. Dr. Hunter is Vincent L. Gregory Professor in Cancer Prevention at HSPH.

Media who would like to interview Dr. Hunter should contact Christina Roache at 617-432-6052 or

The paper on which Dr. Hunter is co-author is “Multiple loci identified in a genomewide association study of prostate cancer.” The paper resulted from research conducted by investigators from the National Cancer Institute (NCI) and their partners in the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, including investigators of the Health Professionals’ Follow-up Study based at HSPH. Initial results were published in the May 1, 2007 issue of Nature Genetics. The National Cancer Institute has issued an updated press release on the 2008 study. To obtain a copy, contact the NCI Office of Media Relations, 301-496-6641,

Q. Can you briefly describe what you and your team have identified in the Nature Genetics paper? What is a SNP? What is the CGEMS Initiative?

Dr. Hunter: We have reported a set of genetic variations, or SNPs, in at least four regions of DNA that predicts prostate cancer risk. These results came from CGEMS (Cancer Genetic Markers of Susceptibility), a National Cancer Institute Special Initiative to conduct genomewide association studies of breast, prostate, and other cancers in a large-scale collaboration across multiple studies.

Q. Your paper comes on the heels of an article published online on January 16, 2008, in The New England Journal of Medicine that associated SNPs in five chromosomal regions with cumulative increased prostate cancer risk. Last year, multiple papers were published that identified or confirmed SNPs associated with the disease, including two papers on which you were a co-author. How do these various findings fit together?

Dr. Hunter: The NEJM paper assessed how risk increases with the number of risk variants that a man carries. This was based on genetic variants identified last year. The new studies add additional variants associated with risk, and, in our analyses, these further sharpen the gradient of risk associated with inheritance of multiple risk variants.

Q. The papers were made possible by genomewide association studies. What is this tool and how does it help researchers study diseases like prostate cancer?

Dr. Hunter: Genomewide association studies permit us to scan the whole genome for gene variants that are more common in men with prostate cancer than men without the disease. This is done using new technologies that have only been developed in the last two to three years and that assess genetic variation at more than 500,000 points in the genome for each DNA sample tested.

Q. The identification of genes associated with diseases has spurred an emerging industry where people can submit DNA samples to private companies to scan for disease risk. What are your opinions about such screenings?

Dr. Hunter: There is little doubt that testing for inherited risk of cancers such as prostate cancer and many other diseases, such as diabetes and heart disease, will become a routine part of medical practice in the future. These new papers demonstrate, however, that we are still early in the process of identifying the gene variants that are relevant for prostate cancer. It is thus premature to propose widespread screening for prostate cancer or for other diseases. We need to study not only the full list of risk variants, but also the best ways of communicating these risks, as well as what practical steps people can take to make best use of this new information.

Q. Prostate cancer screening in particular seems to present a conundrum. Some forms grow so slowly, they may not need treatment. Others spread far more rapidly. The treatment can cause serious side effects, including impotence. If a man could assess his prostate cancer risk from personal genome profiling, why should he not pursue that option?

Dr. Hunter: One of the problems with prostate cancer is that we still cannot readily distinguish between the rapid-growing and slow-growing forms of the disease. This suggests that an early diagnosis and treatment of the disease does not always confer benefit. More frequent screening and early detection of prostate cancer is not guaranteed to reduce death from prostate cancer to the extent it does for cancer in many other organs.

Q. According to the CDC, prostate cancer is the most common form of cancer, other than some kinds of skin cancer, among men in the United States. What are some of the known risk factors?

Dr. Hunter: Prostate cancer is one of the most enigmatic forms of cancer. Until these new genetic findings started to become available two years ago, the only established risk factors were age, family history, and African ancestry.

Q. What role do scientists think genes play in prostate cancer risk?

Dr. Hunter: Family history is one of the few established risk factors, suggesting that inherited gene variants are associated with risk.

Q. Do you have take-home messages for men about prostate health and cancer risks?

Dr. Hunter: The importance of these papers is that we are making progress in understanding the biological basis of prostate cancer. This progress should pay off in ways to prevent, and maybe treat, the disease. Over time we should learn how to use this new information on inherited risk to focus screening for prostate cancer in a way that will reduce morbidity and death from prostate cancer. At this point, the information is just too new to be ready for screening for risk.

Dr. Hunter co-wrote a Perspective, “Letting the Genome out of the Bottle — Will We Get Our Wish?”, in the January 10, 2008 issue in The New England Journal of Medicine. Also, you may listen to a podcast of Dr. Hunter discussing genome profiling.

“Multiple loci identified in a genome-wide association study of prostate cancer.” Gilles Thomas et al., Nature Genetics, published in advance online February 10, 2008, doi:10.1038/ng.91.

In addition to Dr. Hunter, CGEMS is co-led by Stephen Chanock , M.D., Gilles Thomas, M.D., Ph.D., and Robert Hoover, M.D., Sc.D., all of the National Cancer Institute.


For more information, contact:
Christina Roache