Posted on 04/01/2007 5:56:57 PM PDT by neverdem
Contact: Jennifer Chan chanj@usc.edu 323-442-2830 University of Southern California
A study led by researchers at the Keck School of Medicine of the University of Southern California (USC) and Harvard Medical School has identified seven genetic risk factors—DNA sequences carried by some people but not others—that predict risk for prostate cancer. According to the study's findings, these risk factors are clustered in a single region of the human genome on chromosome 8 and powerfully predict a man's probability of developing prostate cancer. The paper will be published in the online edition of Nature Genetics on April 1.
"The study has identified combinations of genetic variants that predict more than a fivefold range of risk for prostate cancer," says senior author David Reich, assistant professor of genetics at Harvard Medical School and associate member of the Broad Institute of Harvard and MIT. "Both high- and low-risk combinations of variants are common in human populations."
"The identification of these genetic variants is an important step in helping us understand the higher risk for prostate cancer in African Americans compared with other U.S. populations and, more importantly, why some men develop prostate cancer and others do not," says lead author Christopher Haiman, assistant professor of preventive medicine at the Keck School of Medicine of USC.
While the HMS/USC team identified seven genetic variants on chromosome 8, two other studies published in the same issue of Nature Genetics highlight the importance of this region in prostate cancer and each provides independent support for the findings presented by the HMS/USC team. One of the studies is from deCODE Genetics in Iceland while the other is led by Dr. Gilles Thomas and Dr. Stephen Chanock at the National Cancer Institute. Together, the three studies provide robust evidence of the role genetic variants play in prostate cancer.
According to the HMS/USC study, the seven genetic variants each independently predict risk for prostate cancer, with the predictive strength varying depending on the variant. Because almost all the risk factors were of highest frequency in African Americans, they may contribute to the known higher rate of prostate cancer among African Americans compared with other U.S. populations. The predictive power of the variants may also be useful in the prevention of prostate cancer. "Clinical testing of these genetic variants may help us identify men who should be prioritized for early prostate cancer screening and prevention efforts," says Reich.
The study also produced novel biological findings. It revealed that each genetic contributor to prostate cancer risk is located outside of the coding regions of genes, in regions previously designated as junk DNA. "The discovery of multiple, independent genetic changes that are in close proximity to one another, but outside of any known gene, suggests that these results may also teach us about novel molecular mechanisms whereby DNA changes can alter risk of disease," says Brian Henderson, the paper's senior co-author and dean of the Keck School of Medicine of USC.
Two papers in 2006 highlighted this same chromosomal region as important in prostate cancer. The company deCODE genetics in Iceland first identified two specific genetic variants that contributed to risk for prostate cancer. The HMS/USC group then published a paper that identified a small region (about 4 million nucleotides, or 1/1,000th of the genome) as likely to contain important genetic risk factors. As part of this study, the HMS/USC group carried out a whole-genome screen for prostate cancer genes in about 2,500 African Americans. The paper suggested that more variants were likely in the region.
To find the additional risk factors in the current study, the team systematically tested genetic changes in this region of the genome in roughly 7,500 African American, Japanese American, Native Hawaiian, Latino, and European American men with and without prostate cancer. The majority of the men studied were drawn from the Multiethnic Cohort Study (MEC), an epidemiological study of more than 215,000 people from Los Angeles and Hawaii created in 1993 by USC's Henderson and Laurence Kolonel of the University of Hawaii. The genetic study of the MEC grows out of a multiyear, ongoing collaboration between USC, the University of Hawaii, and collaborators at HMS and the Broad Institute of Harvard and MIT.
### The study also involved researchers at Massachusetts General Hospital, Dana-Farber Cancer Institute and the University of Michigan.
The National Institutes of Health and the National Cancer Institute provided funding for this study.
HARVARD MEDICAL SCHOOL http://hms.harvard.edu/
Harvard Medical School has more than 7,000 full-time faculty working in eight academic departments based at the School's Boston quadrangle or in one of 47 academic departments at 18 Harvard teaching hospitals and research institutes. Those Harvard hospitals and research institutions include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, The CBR Institute for Biomedical Research, Children's Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, Massachusetts Mental Health Center, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, VA Boston Healthcare System.
Keck School of Medicine of the University of Southern California http://www.usc.edu/schools/medicine/ksom.html
Founded in 1885, the Keck School of Medicine of USC is a major center for basic and clinical biomedical research, especially in the fields of cancer, gene therapy, the neurosciences and metabolic disease. The school today has more than 1,100 full-time faculty members and a voluntary faculty of more than 3,700 physicians. These faculty direct the studies of approximately 650 medical students and more than 400 students pursuing graduate degrees. The school's postgraduate programs provide training for 1,300 residents fellows and interns annually. The Keck School of Medicine has meant better health for people around the globe in all fields of medical care. Through 14 affiliated hospitals, USC physicians serve more than one million patients each year. Hospitals staffed by USC physicians include USC University Hospital, USC/Norris Comprehensive Cancer Center and Hospital, Doheny Eye Institute, Childrens Hospital Los Angeles and the Los Angeles County+USC Medical Center, one of the largest teaching hospitals in the nation.
To Break the Disease, Break the Mold
There are four other guest editorials on cancer linked under OpEd Contributors on the NY Times editorial page if you click this link. It won't bite you. Just avoid the politics.
FReepmail me if you want on or off my health and science ping list.
Thanks ND.
thanks, so are we just sitting ducks waiting for the genes to kick in or are there any nutritional, dietary or lifestyle changes a man can make. What role does DHT play or is that just for the BPH condition.
tHANKS MUCH.
DHT or any androgen doesn't seem favorable for prostate CA. Enter DHT and prostate cancer into PubMed. I'd start with review articles.
Palmetto?
My husband had surgery about 10years ago, for BPH, and ever since then he has been concerned about the possibility of being more at risk for prostate cancer...so I will print out this article, and he can read it...just more information to add, to what other information he already has...thanks...
for some reason, when I saw, "stroke risk", I immediately thought "prostate".
Big study in Japan says green tea lowers stroke risk
NorthJersey.com | 09.14.06 | LINDSEY TANNER
Posted on 10/08/2006 12:19:49 AM EDT by Coleus
http://www.freerepublic.com/focus/chat/1715696/posts
Buried my brother 2 months ago from this.
I'm sorry to read that. You have my sincere condolences.
I think that as time goes by, and genetic research increases in sophistication, we are going to discover that a surprising proportion of "who we are" is "in the genes".
In some ways, we _are_ little more than "sitting ducks" till our genetic programming "kicks in". Witness the women who come from families with near-certainty of breast cancer. I recall reading an article about one woman who had both breasts removed BEFORE she came down with cancer, because the odds of contracting the disease in her family were near 100%.
Of particular interest is that part of the article that describes how certain genetic traits are determined NOT by the coding individual genes themselves, but by certain combinations that lie "outside" genetic coding. I would further speculate that - in time - a similar pattern (with no specific genetic "marker") will be discovered that provides a basic underpinning for sexual orientation, a "programming of the sexual compass", if you will.
There is a saying among the Amish, "in der blut": "in the blood". I suspect that far much more of who we are is in der blut than we know, as of yet. Time will tell.
- John
I can't use the joke I just came up with in response... sunny beaches...
Luckily, the classics never wear out. ;')
Given that prostate cancer is a finding found in most autopsies of any American over 80, it'd be interesting to know how they controlled for age in the study. Instead of a tendency to develop PC, they may have just discovered markers for a tendency to develop PC at an earlier age.
As far as I'm concerned, PC is systemic, and in our culture is a naturally occuring disease of aging.
Apparently, for those with the wrong genes, it can be fatal at younger age. It can really be ugly. I saw metastatic disease which caused the permanent protrusion of the tongue. Otherwise, you live longer and die from something else. I haven't been able searching PubMed or Nature Genetics to find the title and abstract using the senior author's name.
Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men pdf link to the article.
A whole-genome admixture scan in 1,597 African Americans identi- fied a 3.8Mbinterval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD)7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P<4.2109) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it.
That's the abstract, and the latest that I can find from the senior author on prostate cancer.
The early incidence before 72 and equal incidence beyond 72 is consistent with what we're both saying, which is that the issue is early presentation and its correlation with aggressiveness. I have a feeling the next five years is going to produce an assay of some sort that will permit a clear assessment of the aggressiveness of the disease, and thus eliminate the situation where the public health impact of treating those who could have gone untreated is more negative than the impact of not treating those who treatment might have helped.
Ploidy analysis is claimed to be able to make the differentiation right now, but I have my doubts. It's also iffy to do from a core.
Thanks for posting on the topic. It's an important one for a lot of the participants here, and deserves all the exposure it can get.
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