Health disparities: genetics plays an important role in cancer detection, prognosis among minorities

SAN DIEGO – Research reported at the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, suggests that poorer outcomes for breast cancer and prostate cancer among minorities may be due to biologic factors. In addition, researchers present a new theory on why a recent decline in breast cancer rates was less pronounced among African-American women, and offer data on a relatively simple means of reducing racial disparities in breast cancer care.

Gene expression profiling reveals tumor immunobiological differences in prostate cancer between African-American and European-American men: Abstract 512

Prostate cancer appears to be distinctly different in African-American men compared with European-American men, according to researchers at the National Cancer Institute (NCI) who found significant differences in expression of numerous genes in tumor samples taken from the two racial groups.
Many of these genes were related to inflammation and immune system regulation, suggesting that pathogens could be involved in race/ethnic differences that lead to the development of these tumors, the researchers say. Some of the genes were also linked to cancer spread.
Although further study is needed to confirm their hypothesis of possible viral involvement in cancer, the team believes that these novel findings could help explain why both the incidence of, and death rates from, prostate cancer are increased among African-American men.
“We don’t think the worse outcomes we see in African-American prostate cancer patients are due to issues of socioeconomic and sociodemographic differences alone,” said lead author, Tiffany Wallace, Ph.D., a postdoctoral fellow in the Laboratory of Human Carcinogenesis at the NCI. “So we are trying to understand if differences in genetics and biology play a discernable role, and this study suggests they do.”
NCI researchers obtained gene expression profiles from tumors removed during surgery from 33 African-American and 36 European-American patients using gene microarray technology. They also obtained samples of surrounding non-tumor prostate tissue from seven of the African-American and 11 of the European-American patients. They then compared the combined tumor profiles to profiles from non-cancerous tissue, and similar differences in tumor marker expression that other research groups had already detected.
Sorting the samples according to race, they found the differences in gene expression. Of significance was over-expression of indoleamine-2,3-dioxygenase, an immune system modulating enzyme that tumors use to subvert immune-system surveillance, and the “self” antigens HLA-E and HLA-G that additionally inhibit immune responses through different mechanisms.
“These genes are well-known contributors of immunologic tolerance in tumors,” she said. Additionally, there was a distinctive interferon signature in gene over-expression in the African-American patients, which is associated with an immune system response against foreign invaders such as viruses.
One puzzling finding: genes that activate the immune system and genes that suppress it were both more highly expressed in the African-American patients. Wallace says this suggests the immune system is fighting the cause of the cancer, which could be a pathogenic invader. Alternatively, the discovered gene signature may reflect merely the presence of a chronic low-level inflammation that is more prevalent in the tumors of the African-American patients, she says. It could also mean that prostate tumors in these men have ways of suppressing the immune system, which explains why their tumors are more aggressive, she adds.
“Something is different in the tumor microenvironment between the group of patients we studied and it has to do with tumor immunobiology,” Wallace said. “We are intrigued with these findings, which we are continuing to research.”