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Genetic Differences Linked to Higher Risk, Severity of Prostate Cancer in African-American Men

October 2011 Vol 4, No 7

WASHINGTON, DC—Genetic differences among African-American and white men seem to be root causes of the prostate cancer disparities between the 2 groups, according to new data. Prostate cancer is the second most common cancer among men in the United States, with occurrences and mortality rates higher in African- American men compared with white men. Studies show that prostate cancer is a disease conferred by multiple gene mutations, numerous alterations in gene expression, and changes in genome composition. Researchers, therefore, are investigating the genetic predispositions and oncogenic networks associated with observed prostate cancer disparities.

“There are a lot of socioeconomic and environmental factors that create differences in levels of prostate cancer in these 2 groups,” said one study investigator Bi- Dar Wang, PhD, assistant research professor of pharmacology and physiology at George Washington University, in Washington, DC. “We’ve found that genetic elements play a role in these disparities as well.”

Wang and colleagues analyzed normal and cancerous prostate tissue samples from African-American and white men who underwent prostate biopsies. They looked at 2 key genetic pieces: messenger RNA (mRNA), which carries codes from DNA that then are used to make proteins; and microRNA, shorter RNA strands that regulate that process by binding to mRNA and interrupt the gene expression. The results showed enough differences between African-American and white men to determine that each race has “population-specific” mRNA and microRNA.

Overall, the researchers found nearly 400 mRNAs were expressed differentially between the cancerous prostate tissues of African-American and white men. These differences are crucial because mRNA and microRNA affect the biological pathways by which prostate cancer tumor formation is either promoted or stopped, according to Wang.

“It is still too early to conclude any novel treatment strategy based on our results. However, the genomic analyses of prostate cancers have revealed that differential mRNA and microRNA expression and the associated gene network rewriting may be critical in prostate cancer health disparities,” said Wang.

He said these findings will help lead to a better understanding of the molecular mechanisms underlying prostate cancer disparities and may lead to the development of novel strategies for prostate cancer detection and personalized treatment for African-American men. “We may be able to identify better biomarkers for early detection and treatment in African Americans. Their tumors are slightly different in terms of genetic factors,” Wang said in an interview with The Oncology Pharmacist.

In a separate study just released, investigators found that a high intake of calcium causes prostate cancer among African-American men who are genetically good absorbers of the mineral (J Bone Miner Res. September 1, 2011. Epub ahead of print). “High dietary intake of calcium has long been linked to prostate cancer but the explanation for this observation has been elusive,” said study investigator Gary Schwartz, PhD, associate professor of cancer biology, urology, and public health sciences at Wake Forest Baptist Medical Center, Winston- Salem, North Carolina.

Schwartz and his team studied 783 African-American men, 533 of whom were diagnosed with prostate cancer. The investigators studied the effects of genotype, calcium intake, and diet– gene interactions. The study is one of the few to explore genes related to calcium absorption or to examine diet in a large African-American population.

Although prostate cancer is 36% more common among African Americans than in non-Hispanic whites, data on the diet–cancer link primarily come from populations of Caucasian origin. The team targeted a genetic allele that is more common in populations of African origin than in other populations and is associated with regulating the absorption of calcium.

The study found that men who reported the highest intake of calcium were 2 times more likely to have localized and advanced prostate cancer than those who reported the lowest. Men with a genotype associated with poor calcium absorption were 59% less likely to have been diagnosed with advanced prostate cancer than men who genetically were the best absorbers of calcium. The researchers found that among men with calcium intake below the median, genetically poor absorbers had a 50% decreased risk of having advanced prostate cancer than the best absorbers.

“It may be possible in the future to personalize prevention using this type of genetic knowledge,” said Schwartz. “We now have a better understanding of why calcium in the diet may increase the risk for prostate cancer and who is at increased risk. If our results are confirmed, it gives much better insight into the preventable causes of prostate cancer. So if I know I’m a good absorber of calcium, I may want to be careful about my diet and about the use of calcium supplements.”

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