Potential biological factor contributing to racial disparities in prostate cancer

December 08, 2013

ATLANTA -- Researchers have uncovered a potential biological factor that may contribute to disparities in prostate cancer incidence and mortality between African-American and non-Hispanic white men in the United States, according to results presented here at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Dec. 6-9.

In the United States, African-American men are 1.5 times more likely to develop prostate cancer and more than twice as likely to die from the disease compared with non-Hispanic white men.

"The causes of prostate cancer disparities are numerous, complex, often interrelated, and only partially understood," said David P. Turner, Ph.D., assistant professor in the Department of Pathology and Laboratory Medicine at the Medical University of South Carolina in Charleston. "We have identified a potential relationship between sugar-derived metabolites and cancer that may provide a biological link with socioeconomic and environmental factors known to contribute to prostate cancer disparities.

"As our bodies use the sugars that we consume for energy they generate waste products, or metabolites, including molecules called advanced glycation end products, or AGEs," Turner explained. "AGEs naturally accumulate in our tissue as we grow older, and they have been implicated in diseases associated with aging such as diabetes, heart disease, and Alzheimer's disease. They can also cause increased inflammation and the generation of potentially harmful chemicals known as reaction oxygen species, which both promote cancer.

"Critically, a common source of the AGEs that accumulate in our bodies is the foods we eat, which has significant implications for cancer health disparities and our overall health.

"We found that AGE levels were highest in African-American men with prostate cancer," said Turner. "Because obesity, poor eating habits, and an inactive lifestyle all promote AGE accumulation, and these factors are often more evident in African-Americans, we hypothesize that there is a link between these factors that could help explain why African-American men are more likely to develop prostate cancer and die from the disease."

Turner and colleagues examined circulating and intratumoral AGE levels in 16 African-American and 16 non-Hispanic white men with prostate cancer. They found that AGE levels were higher in serum from cancer patients compared with individuals without cancer. When analyzing AGE levels in prostate tumor samples, levels were highest in tumor samples from African-American patients. In addition, AGE levels in prostate tumors correlated with levels of a molecule to which AGEs bind to mediate their effects, called receptor for AGE (RAGE).

"We think that the AGE-RAGE signaling pathway promotes prostate cancer and that increased AGE accumulation may represent a biological mechanism promoting prostate cancer disparity," said Turner.
-end-
This study was funded in part by the National Institutes of Health as part of the South Carolina Cancer Disparities Research Center. Turner declares no conflicts of interest.

To interview David Turner, contact Tony Ciuffo at ciuffo@musc.edu or 843-792-2626. For other inquiries, contact Jeremy Moore at jeremy.moore@aacr.org or 215-446-7109.

Follow the AACR on Twitter: @AACR
Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit
http://www.AACR.org.

Abstract Number: PR10

Presenter: David P. Turner, Ph.D.

Title: Advanced glycation end-products are increased in prostate cancer and may promote racial disparity

Authors: David P. Turner1, Victoria J. Findlay1, Lourdes M. Nogueira1, Sadia Robinson2, Emily Kistner-Griffin1, Laura Spruill1, Ryan Y. Turner1, Mahtabuddin Ahmed2, Judith D. Salley2, Marvella E. Ford1. 1Medical University of South Carolina, Charleston, SC, 2State University of South Carolina, Orangeburg, SC.

African American cancer patients are more likely to die of their disease than their European counterparts. Our research has identified a potential mechanistic link between carbohydrate derived metabolites and cancer associated pathways which may provide a biological consequence of the socioeconomic and environmental factors that are known to drive cancer health disparity.

Glycation is the non-enzymatic glycosylation of sugar moieties to biological macromolecules such as protein and DNA which produces reactive metabolites known as advanced glycation end products (AGE's). AGE's accumulate in our tissues as we grow older and drive many of the complications associated with diseases displaying health disparity including diabetes, metabolic syndrome, Alzheimer's and heart disease. Low income, obesity and an inactive/sedentary lifestyle are established factors driving cancer health disparity. Apart from their production during normal metabolism, AGE's are also formed through the ingestion of food and by external environmental factors such as lack of exercise. AGE content in the Western Diet has consistently increased over the last 50 years due to increased consumption of sugar laden and cheap processed/manufactured foods which are high in reactive AGE metabolites and can promote obesity.

We therefore examined circulating and intra-tumoral AGE metabolite levels in clinical specimens and identified a race specific, tumor dependent pattern of accumulation in prostate cancer serum and tumor. In mouse xenograft models, AGE accumulation was highest in the more aggressive tumors. One way AGE's mediate their deleterious effects is by functioning as ligand for the trans-membrane receptor for AGE (RAGE). In diabetes and other diseases, the AGE-RAGE signaling axis is a pro-inflammatory pathway leading to the upregulation of pro-inflammtory cytokines through increased NFkB activation. Higher AGE levels in prostate tumors corresponded with higher RAGE expression and increased NFkB transcriptional activity. In immortalized prostate cancer cell lines AGE treatment increased cancer associated processes and RAGE expression levels. Loss of function studies show that AGE mediated increases in cancer associated processes was dependent upon RAGE expression.

These data implicate the AGE-RAGE signaling axis as a potential biological mechanism promoting prostate cancer and indicate that increased AGE accumulation may represent a biological mechanism promoting prostate cancer disparity.

American Association for Cancer Research

Related Prostate Cancer Articles from Brightsurf:

Low risk of cancer spread on active surveillance for early prostate cancer
Men undergoing active surveillance for prostate cancer have very low rates - one percent or less - of cancer spread (metastases) or death from prostate cancer, according to a recent study published in the Journal of Urology®, an Official Journal of the American Urological Association (AUA).

ESMO 2020: Breast cancer drug set to transform prostate cancer treatment
A drug used to treat breast and ovarian cancer can extend the lives of some men with prostate cancer and should become a new standard treatment for the disease, concludes a major trial which is set to change clinical practice.

Major trial shows breast cancer drug can hit prostate cancer Achilles heel
A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.

The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.

Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.

First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.

Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.

CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.

Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.

Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.

Read More: Prostate Cancer News and Prostate Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.