Searching the Genome to Understand Cancer Disparities among Minority Populations
Mapping the genome has brought new insight into the causes and progression of diseases such as cancer, opening up new avenues of research to improve prevention, diagnosis, and treatment. However, the human genome has yet to shed light into why some minority populations experience disproportionately high rates of common cancers.
New research funded by grants from the American Recovery and Reinvestment Act (ARRA) aims to change that. Using Recovery Act funds, many of the nation’s top cancer research institutions have forged collaborations to amass some of the largest study populations ever assembled for cancer research in racial/ethnic minority groups. Researchers hope that, by identifying genetic variants that are more or less common in specific minority groups, they can better understand why some populations experience disproportionately high rates of certain cancers. Such understanding could ultimately lead to better prevention strategies as well as more-effective treatments.
Seeking a Genetic Basis for Prostate Cancer in African-American Men
Prostate cancer is one of the leading causes of cancer death among men, and prostate cancer incidence and death rates are particularly high among men of African ancestry. In the United States, African Americans are more than 1.5 times as likely to develop prostate cancer and more than twice as likely to die of the disease as European-American men. Researchers have long suspected that genetic factors must play a role in this disparity but until recently have lacked the technology and funding to examine the issue.
With a Recovery Act grant from the National Cancer Institute (NCI), Christopher Haiman, Sc.D., of the University of Southern California has begun to analyze DNA from 5,130 African-American men with prostate cancer and 5,228 African-American control men in a genome-wide association study (GWAS) to identify common genetic risk factors for the disease among this population. Nearly every investigator in the United States who has established case-control studies of prostate cancer among African Americans is collaborating in this project by providing data and DNA specimens for the men in their studies.
“The ethnic differences in the risk of prostate cancer begged for a genomic study among men of African ancestry,” said Dr. Haiman. “All other funding to date has been focused on men of European ancestry.”
According to Haiman, by combining the cases from multiple prostate cancer investigations, the study has the potential to uncover new regions of the genome whose association with prostate cancer had not been discovered in previous studies.
“We believe this will help us understand who may be more susceptible to the disease,” said Haiman. “It might also help us develop new approaches for preventing prostate cancer, perhaps leading to the development of new agents that target the genes that are involved in making people more susceptible in the first place.”
Ultimately, Haiman hopes that this large collaborative project will become a model for addressing health disparities in other diseases and populations.
“To understand disparities, you have to study the populations where those disparities exist,” he said.
Learning about Lung Cancer Susceptibility among African Americans
Lung cancer is another disease that affects African-American men at a much higher rate than the general population. Through Recovery Act funding, NCI is enabling collaboration from diverse institutions including Barbara Ann Karmanos Cancer Institute/Wayne State University, University of Texas M.D. Anderson Cancer Center, and University of California San Francisco, who together can pool DNA from nearly 2,000 African-American lung cancer patients and 2,000 control subjects in a GWAS to identify genetic variants that are associated with lung cancer. Teams at these institutions have retained and hired new investigators, research assistants, lab technicians, and clinical coding specialists.
According to Ann Schwartz, Ph.D., M.P.H., principal investigator from Barbara Ann Karmanos Cancer Institute/Wayne State University, there is greater genetic diversity among African-American populations than European-American populations. This greater genetic variation among African Americans means that more genetic markers need to be studied in large study populations to accurately identify regions of the genome associated with cancer risk. Because no one institution has had the resources to generate a sizeable enough study population, the Recovery Act funding from NCI has been vital in helping researchers at different institutions collaborate.
“Previous genome-wide association studies for lung cancer have not included African Americans. Because of the greater genetic variation in African Americans, you need to cover more areas of the genome to make sure you’re assessing all of the variation,” said Dr. Schwartz. “Until recently, studies with sufficient marker coverage to account for this variation among African Americans have not been possible.”
Christopher Amos, Ph.D., principal investigator with The University of Texas M.D. Anderson Cancer Center, agrees. “The ARRA funding provided immediate assistance to the lab so that we could process our samples and integrate them with the other groups,” he said. “There’s no way that a project of this size and scale could have been possible without the speed and flexibility of the Recovery Act grants. Under a normal funding process, getting this project up and running would have taken years. This took us six months.”
As with the prostate cancer study, the lung cancer GWAS ultimately hopes to improve screening, prevention, and treatment. “Once we understand more about the pathogenesis of lung cancer, hopefully we can better target treatment and prevention efforts,” said Dr. Schwartz. “It’s also likely that what we learn in this African-American population may help us understand lung cancer in other populations. We hope that our findings will help expand what we know about lung carcinogenesis more broadly. We may find mutations that are prevalent in African-American patients but also occur in other groups as well, just at different frequencies.”
Learn more about what NCI is doing to overcome cancer health disparities: http://www.cancer.gov/cancertopics/disparities.