by
JACQUELINE STRAX
PSA Rising, New York, July 27, 2003 -- Black men face a much higher risk of prostate cancer than whites, and a higher risk of dying from the disease. Today, researchers who believe they are zeroing in on answers say that too few African-American men have ever been involved enough to find out if promising genetic findings apply to African-American as well as Caucasian men.
Early this year, researchers at the Center for Human Genomics reported that a gene called macrophage scavenger receptor 1, or MSR1, plays an important role in inherited and non-inherited prostate cancer.
Normally this gene works as part of the immune system to protect cells from damage. When it is damaged or altered itself, cancer may arise.
Now a new study by University of Michigan Health System researchers has found that changes in this gene, MSR1 play a role in prostate cancer in African-American men. The study, which will be published in the July 1 issue of the American Association for Cancer Research's journal Cancer Research, came from a larger project called the Flint Men's Health Study, aimed at identifying risk factors for prostate cancer in African-American men. It is a rare effort to recruit large numbers of African-Americans in a population-based research study.
"African-American men have the highest incidence of prostate cancer in the world. The severity is higher and they tend to die more quickly after diagnosis," says Kathleen Cooney, M.D., the study's senior author and associate professor in the research faculty of Internal Medicine and Surgery at the U-M Comprehensive Cancer Center. "We don't know why this is, but part of the difficulty is that African-American men are underrepresented in most genetics studies."
In this particular study, researchers looked at African-American men ages 40-79 who live in Flint, Mich. Researchers compared DNA samples from 134 African-American men diagnosed with prostate cancer with samples from 340 African-American men without prostate cancer. Five common variants and five recently reported mutations were analyzed. Researchers determined that rare germ-line MSR1 mutations were associated with an increased prostate cancer risk.
The findings echo previous studies' results that showed the same link in Caucasian men.
"This study adds to an expanding body of evidence in support of the germ-line MSR1 mutations as risk factors for prostate cancer. [Click here for pop-up More about Germ Lines]. Although our study was modest in size, the public health burden of prostate cancer in the African-American community warrants further attention to potential genetic risk factors," says David Miller, M.D., a resident in Urology at the U-M Medical School and lead author of the report.
While scientists believe there is a strong hereditary link in prostate cancer, it's been difficult to pin down the exact genes involved in this disease. Many men develop prostate cancer later in life, and some men may die before prostate cancer even develops, making it difficult to trace the disease through generations of families.
Knowing the genetic markers involved in prostate cancer could help determine which men are at highest risk. Currently, physicians say men with a family history of the disease and African-American men are at the highest risk. Genetic risk factors could help narrow that down even further, indicating when more aggressive tests or therapies are necessary.
In addition to this paper, the Flint Men's Health Study has looked at prostate-specific antigen, or PSA, levels and differences in the frequency and severity of prostate cancer symptoms in African-American men. The study began collecting data in 1996 and identified 817 eligible African-American men ages 40-79 to participate. The study subjects were recruited from Flint, Mich., an urban area north of Detroit with a high African-American population. Of the eligible group, 369 participants underwent an interview, clinical exam and serum test. Researchers contacted the participants again in 2000 for further testing; 183 took part in the second wave.
Aside from the large African-American participation, the study is unusual because it recruited people through the community, not through a hospital setting. Part of the difficulty UMHS faces in recruiting African-Americans for clinical trials is the low population of African-Americans seen at its own hospitals. Only about 5 percent of the hospital's population is African-American.
"Other studies have looked at hospital-based populations, but few have gone into the community to recruit a population like we did with the Flint Men's Health Study," says Aruna Sarma, Ph.D., assistant research scientist in the Department of Urology and coordinator of the Flint study.
In addition, there are cultural and attitudinal barriers toward medical research within the African-American community that need to be overcome.
Some African-Americans may think back to the Tuskegee Study, a 40-year study of the effects of syphilis on African-American men. Even though an effective treatment for syphilis was discovered in the 1950s, the study continued for another 20 years and the men involved were neither given treatment nor told of any treatment option.
"There is a major issue of trust," says Willie Underwood, M. D., lecturer in the UMHS Department of Urology, That combined with cultural attitudes toward research -- bred in part from the Tuskkegee study. -- makes it difficult to develop fruitful relationships like Flint Men's Health study. Now there are groups, such as University of Michigan, making efforts to help build African-American community. Without participation of African-Americans in studies, we can answer complex questions about their health."
The Flint Men's Health Study was funded by a U-M Specialized Program of Research Excellence, or SPORE, grant in prostate cancer. Additional funding came from the U-M Office of Research and Minority Health, the Department of Urology and several Flint-based community organizations -- FAITH, Genesee County Health Department and QUEST Laboratories.
The study has yielded eight published papers to date, with more than 35 abstracts written or presented and at least five projects in which data are still being analyzed.
Although the Flint Men's Health Study is not enrolling further participants, researchers say it's crucial for African-Americans to enroll in mainstream research studies going on throughout the UMHS.
Links and Credits:
For information about UM's ongoing research opportunities, go to http://www.med.umich.edu/gcrc/.
Each generation of sexually-reproducing organisms is dependent upon the germ line of its predecessors for its existence. Likewise, the production of succeeding generations is dependent upon the current generation's germ line. Thus, the germ line is the link that ensures the very survival of these species. The germ line is also the vehicle of evolution. Transmission of mutations and recombination of existing genes in germ line cells generates the diversity that, in turn, generates species diversity. Scientists have developed tools that enable them to manipulate the germ line in a variety of ways, such as freezing germ line cells to store them for later utilization in fertilization and altering their genetic composition.
Quote from The Ark of Life: The Germ Line: http://www.ucalgary.ca/UofC/eduweb/virtualembryo/ark.html
Germ-line Mutations of the Macrophage Scavenger Receptor 1 Gene
Association with Prostate Cancer Risk in African-American Men
David C. Miller, S. Lilly Zheng, Rodney L. Dunn, Aruna V. Sarma, James E. Montie, Ethan M. Lange, Deborah A. Meyers, Jianfeng Xu and Kathleen A. Cooney
Departments of Urology
and Internal Medicine [K. A. C.], University of Michigan, Medical School, Ann Arbor, Michigan 48109-0946, and Department of Public Health Sciences and Center for Human Genetics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1063 Published in Cancer Research 63, 3486-3489, July 1, 2003]
© 2003 American Association for Cancer Research
Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.
Xu J, Zheng SL, Komiya A, Mychaleckyj JC, Isaacs SD, Chang B, Turner AR, Ewing CM, Wiley KE, Hawkins GA, Bleecker ER, Walsh PC, Meyers DA, Isaacs WB.
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
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