Genetic and Behavioral Differences Add to Prostate Cancer Disparities
November 29, 2007
ATLANTA - African-American men face an observable disadvantage versus Caucasian men when it comes to prostate cancer survival. Not only is prostate cancer detected later in African-Americans, it is often more aggressive and harder to treat.
Findings on the social and biological factors influencing disparities among African-American men are reported today at the American Association for Cancer Research conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, being held November 27-30 in Atlanta. New research on the effects of weight, genetics and even religious beliefs on prostate cancer are among the day's highlights.
An exploratory investigation of prostate cancer knowledge, cultural beliefs, and values among black men of West African ancestry, Abstract no. A-3:
A survey of African-American and Nigerian men shows that African-American men are more fatalistic in their cancer beliefs and less likely to exhibit religious coping skills, according to a team of researchers based at Florida A&M University and H. Lee Moffitt Cancer Center.
Among all American ethnic groups, African-American men tend to suffer disproportionately from aggressive prostate cancer, which is often detected at a much later stage. This survey provides a baseline of African-American cultural beliefs and values toward prostate cancer that might serve in crafting prostate cancer awareness programs, the researchers say.
"Men who have fatalistic beliefs about prostate cancer, for example, may be less likely to take the steps necessary to prevent cancer or undergo cancer screening to detect cancer," said lead researcher, Folakemi T. Odedina, Ph.D., professor and director of Florida A&M's Economic, Social & Administrative Pharmacy program. "These are cultural beliefs that compound existing health disparities for African-American men, and we must understand these beliefs if we are to understand how to change behavior."
The study is the first to compare cultural knowledge and beliefs among African-American, indigenous West African and West African immigrant men in an attempt to uncover the cultural components of the prostate cancer disparity. According to Odedina, both Nigerian men and West African immigrants to the United States are reported to have a lower incidence of prostate cancer than African-Americans, although some studies conflict regarding the magnitude of this difference.
The survey, conducted by Odedina and her colleagues in the United States and Nigeria, gauged the attitudes of African-American men, Nigerian men, and Nigerian men who have moved to the United States.
"We decided to understand prostate cancer health disparities in African-American men by separating environmental and psycho-social factors from genetics," Odedina said. "Since the Trans-Atlantic slave trade took so many men from West Africa - more than a third of slaves came from the Nigeria region, alone - African-American and West African men have similar genetic backgrounds, but much cultural dissimilarity."
Odedina and her colleagues surveyed 81 African-American men from Orlando, Florida; 121 Nigerian immigrants living in Houston, Texas; and 128 men in Abeokuta, Nigeria. The survey explored cultural beliefs thought to impact cancer survival, such as cancer fatalism, religious coping (the ability to use faith to help manage disease treatment), temporal orientation (a measure of an individual's focus on the past, present or future) and acculturation (the degree to which an individual from a non-dominant culture takes on the behavior and trappings of the dominant culture).
Among their findings, the researchers say that while African-American men may know more about prostate cancer, they are less likely to possess cultural beliefs and values that could improve cancer detection and control. In contrast to Nigerian men, African-American men are 22 percent more likely to hold fatalistic beliefs about cancer and 60 percent less likely to possess the religious coping skills that could sustain them through cancer therapy, Odedina says. Among African-American men and women, fatalistic perspectives have also been reported to affect cervical cancer, breast cancer, colorectal cancer and fecal occult blood testing, she says.
Although the impact of religion and spiritualism on cancer prevention or detection has not been well documented in the literature, it has been suggested that it may deter women from seeking treatment for breast cancer, Odedina says.
Association between PSA and leptin, adiponectin, HbA1c, or C-peptide among African-American and Caucasian men. Abstract No. A-33:
Obesity and diabetes might mask the onset of prostate cancer in African-American men, making it difficult to detect early-stage and treatable prostate cancer in a population of men already prone to aggressive cancer, according to researchers at Vanderbilt University. Their findings examine the link between prostate-specific antigen (PSA) - a blood marker which at elevated levels indicates the presence of prostate cancer - and biological markers for obesity and diabetes.
"African-American men, among all racial groups, are more likely to be diagnosed with prostate cancer at an advanced stage and are also more likely to die from prostate cancer," said Jay H. Fowke, Ph.D., M.P.H., an assistant professor of Medicine and cancer epidemiologist at Vanderbilt-Ingram Cancer Center.
According to Fowke, obese men are also more likely to present with prostate cancer at an advanced stage. Most prostate cancer is diagnosed in response to a PSA test, and a high body mass index (BMI) often corresponds with lower blood PSA levels.
"Diabetes and metabolic disturbances associated with insulin regulation are more common among African-Americans compared to Caucasians, and metabolic disorders associated with obesity and diabetes may lower PSA levels and may cause a delay in referring a patient for a biopsy," Fowke said. "This may be in part why we often don't detect prostate cancer in African-American men until it is already fairly advanced."
Given the increasing rates of obesity and diabetes among African-Americans, Fowke and his colleagues sought a better understanding of the relationship between race, metabolic disorders and PSA levels used to detect early-stage prostate cancer.
The researchers examined participants in the Southern Community Cohort Study, a National Cancer Institute-funded initiative that monitors the health of 90,000 men and women between the ages of 40 and 79 throughout the southern United States. The researchers randomly selected 121 African-American men and 121 Caucasian men; each group had the same proportion of obese and overweight men, as determined by their BMI. Study participants had no prior diagnosis of cancer or diabetes.
From each participant's blood sample, the researchers compared PSA levels with the amounts of HbA1c, C-peptide, leptin and adiponectin - naturally occurring blood-borne molecules that have a biological role in metabolism, insulin activity, or the function of fat cells. Among African-Americans, PSA levels were 50 percent lower among men with higher levels of C-peptide, a biomarker that reliably indicates an increase in insulin. This association was especially prevalent among obese African-American men, Fowke says. PSA levels also declined somewhat among obese Caucasian men with high C-peptide levels, but this relationship was not as strong as it was in the African-American group.
The researchers saw a similar pattern in Caucasian men regarding the diabetes biomarker HbA1c, where PSA levels were 50 percent lower among men with higher levels of HbA1c. PSA levels were not associated with HbA1c in the African-American group, perhaps suggesting that there may be differences between Caucasian and African-American men in the way PSA responds to obesity.
"There are a number of complex components related to obesity and insulin activity, and we are seeing that metabolic disturbances can have an effect on PSA levels," Fowke said. "It doesn't invalidate PSA screenings, but it does demonstrate that we need research to better understand how obesity and diabetes may be affecting our ability to detect early-stage prostate cancer among African-American men at high-risk for advanced prostate cancer."
Potential role for nuclear matrix proteins hnRNPH1 and SAFB-2 in ethnic disparity of prostate cancer, Abstract no. B-99:
Researchers based at Tulane University report the discovery of biological markers of prostate cancer which are involved in the growth of tumor cells, shedding light on the genetic basis for the prostate cancer burden faced by African-American men.
In prostate tumors samples taken from African-American and Caucasian men, the researchers found that two proteins are overproduced in 90 percent of tumor cells from the African-Americans studied. These structural proteins, called hnRNP-H1 and SAFB-2, in part comprise the nuclear matrix, the mesh of molecules that serves as the supporting "skeleton" of the cell's nucleus.
"We have employed a unique functional genomics approach to unravel the molecular mechanisms underlying the disproportionate incidence and mortality among African-American men," said Asim B. Abdel-Mageed, D.V.M, Ph.D., associate professor and director of the Molecular Oncology Research program in the Department of Urology at Tulane University School of Medicine.
Currently, prostate specific antigen (PSA) and digital rectal examinations are the two most common methods of detecting prostate cancer. African Americans are typically diagnosed with prostate cancer more frequently and later - when the cancer is at an advanced stage and more aggressive - than any other ethnic group in the United States. According to Abdel-Mageed, earlier detection of prostate cancer might decrease this health disparity. "The target genes may have potential clinical utility as biomarkers or prognostic indicators of disease progression in African-American men independent of a PSA screen," Abdel-Mageed said.
With funding from the National Cancer Institute and American Cancer Society, the researchers compared prostate cancer cells from 50 African-American and Caucasian men, aged 50 to 60, matched so that each group comprised similar tumor grades. Using DNA sequencing and screening techniques to determine the genetic activity of these tumor cells, the researchers demonstrated the increased production of heterogeneous nuclear ribonucleoprotein H1 (hnRNP-H1) and scaffold attachment factor B2 (SAFB-2) in African-American men as opposed to Caucasians.
In addition to their role as potential blood-borne biomarkers for disease screening, the researchers are excited by the role these proteins play in chemical pathways that control disease progression. "Both of these genes share many structural and functional similarities, including possession of messenger RNA binding sites that could allow them to regulate how other genes are read from the DNA," said Abdel-Mageed.
Through related means, Abdel-Mageed says, these proteins are somehow involved in the relationship between hormones and prostate cancer progression. The researchers determined that hnRNP-H1 protein, in particular, binds to and activates the androgen receptor (AR), a nuclear protein that serves as an intermediate that allows male hormones from the bloodstream, such as testosterone, to activate genes encoded in the DNA. Testosterone and other hormones have been shown to influence prostate cancer growth, Abdel-Mageed says.
"Similarly, SAFB-2 was shown to have a role in regulation of hormone-related genes. "Based on these data, we believe their selective expression may represent a novel a mechanism for disease progression and development of hormone refractory disease in African Americans," said Abdel-Mageed.
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The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; healthcare professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
In Atlanta (November 27-30):