Abstract
There is a clear disparity in the research that is focused on African Americans and other minority/ethnic populations. If one accepts that there are likely biological differences in tissues from different racial and sex groups, there may be reluctance by some investigators to include different racial, ethnic and sex subgroups in a study in order to make the data of the study more uniform. This is certainly acceptable provided that there also is a study of the next most common racial subgroup. In my research, I typically focus on both European Americans and African Americans, but analyze these groups separately. This is relatively easy for a tissue primarily associated with one sex (e.g., prostate cancer or breast cancer); however, for colorectal cancer, there will be 4 groups to compare and hence a much larger number of cases must be collected and analyzed.
In my view, much of the racial disparity in research is secondary to an inadequate availability of tissues from non-European racial/ethnic populations as well as cell lines developed from these populations. There may also be too great a reliance on self-identified race/ethnicity in the characterization of available tissues. Why are tissues from non-European race/ethnic groups more difficult to obtain? In some cases data on race/ethnicity of patients may not be collected making tissues from minorities difficult to identify. The lower availability of tissues from minorities is based on several variables including the types of tissues that are required for the research. Currently, the easiest tissue to obtain is from paraffin blocks originally used in diagnosis because samples from paraffin blocks can be used readily if the samples are not too small (e.g., a biopsy). This access will change if the proposed changes to the common rule are adopted (Grizzle 2015). In contrast, fresh viable tissue may be the most difficult to provide because collection and use of such tissues must be rapid and quality control may not be available when the fresh sample is provided to the researcher. Also, successful collection of viable tissue as well as fresh frozen tissue requires an organized biorepository.
In some cases, such as prostate, African Americans frequently do not elect radical surgery, but instead choose radiation therapy. For this reason, only small paraffin embedded biopsy samples are available. However, this tissue frequently may not be provided for research as it represents the only record of the disease and should be retained because new therapies may require verification of molecular markers in the biopsy tissues in order for patients to be eligible for a specific targeted therapy. There may also be decreased availability of tissue from patients with other cancers, such as pancreatic cancer, in which patients may present with advanced cancer for which surgical therapy is not utilized. Thus, we have lack of availability based on the types of cancer and use of non-surgical therapy so that scant tissue is available to support research.
Many cancers may be treated with some type of therapy (e.g., radiation, chemotherapy) prior to surgery (neoadjuvant therapy). There is minimal understanding of the effects of neoadjuvant therapy on tissues used in research; however, it is very unlikely that such tissues would represent the original primary tumor or metastatic lesions. For example, whole subgroups of cell types in a cancer may be molecularly changed or killed by neoadjuvant therapy. Hence, such tissues may not be as useful in general biomedical research.
Most research is performed at academic medical centers and associated universities. Many cancers treated at tertiary referral hospitals associated with university medical centers are more advanced and hence, do not adequately represent typical primary cancers. Consider colorectal cancer. Most primary colorectal cancers are surgically removed at community hospitals. Because such hospitals are focused only on health care and not research, no viable frozen tissues typically are available from these facilities and frozen tissues are not stored; thus, only paraffin embedded paraffin blocks may exist. Also, community hospitals may be very reluctant to participate in research because it is not their primary goal. Of critical importance, most African Americans are treated for colorectal cancer at these community hospitals and not at academic centers. This is also the situation for breast, prostate, cervical, and ovarian cancers. In contrast, a larger proportion of lung and pancreatic cancers may be treated at academic centers. Thus, the sites of primary care (surgery) reduce the availability for research of cancer tissues from minority populations. Also, the area of the USA in which academic centers are located may have variable African American and other minority populations. For example, I found it very difficult to obtain cancers from African Americans at academic centers in Ohio because the centers only treated a small number of African Americans.
How can the availability of tissues from African Americans be increased? This issue varies with the type of tissue and the most frequent sites at which medical care is delivered. For example, to increase the availability of prostate cancer samples from African Americans, we took two independent approaches. First, we applied a tissue print technology in which nitrocellulose blots were taken of fresh, unfixed biopsy cores of the prostate. Such nitrocellulose prints can provide several hundred nanograms of high quality mRNA and DNA that are useful for identifying genes involved in prostate cancer as well as characterizing the racial admixtures of patients (see abstract of poster presented at this conference by Sandra M. Gaston et al.). The second approach was to enlist a large private practice community urology group (Urology Centers of Alabama) to participate in obtaining tissue prints from African Americans who are a large component of their clinical practice. The tissue print technology can be applied to any cancer for which only small biopsy samples are available and to the characterization by biopsy of potential metastatic and/or recurrent sites. Because pancreatic cancer may be too advanced for surgical therapy and/or may have neoadjuvant therapy, we have been successful in consenting patients for obtaining extra fine needle aspirates (FNAs) specifically for research after adequate diagnostic material has been confirmed on the initial FNAs. Such FNAs collected specifically for research have been used successfully in sequencing of pancreatic cancer and for 3-dimensional culture to form “organoids” for the study of pancreatic cancer.
When patients, including minorities, are evaluated for cancer, lymphocytes from samples of blood can be immortalized to provide a continuing source of germline DNA from patients with and without cancer. We also have focused on expanding the use of paraffin embedded tissue in biomedical research by studying the benefits and limitations of using such tissue in research. In addition, we have been able to enlist community hospitals in the Birmingham area in the study of colon cancer.
There are many tissue banks throughout the USA that are underutilized. Many of these banks may have tissues collected from minorities. Because these banks do not advertise the availability of their minority samples or may not provide these samples outside their local medical center, the samples frequently may not be used in research. Investigators who need access to tissues from minority patients should query local biorepositories to determine availability of such samples.
I am principal investigator of a division of the Cooperative Human Tissue Network (CHTN). The CHTN is a group of six academic institutions dedicated to providing research tissues to support biomedical research. These are the Ohio State University, The University of Alabama at Birmingham, The University of Pennsylvania, The University of Virginia, Vanderbilt University, and the pediatric division, Nationwide Children's Hospital. These institutions provide a wide range of human tissues to investigators primarily in North America. The CHTN operates under a prospective model in which investigators request specific tissues and the CHTN collects tissues specifically to meet investigator requirements. To date, the CHTN has provided over 1 million specimens to investigators resulting in ~ 4000 publications. The CHTN is an important resource for providing human tissues samples from African American patients.
Grizzle WE. Missed opportunities and lost lives: Consequences of some proposed changes to regulations on research with human tissues-Letter. Clinical Cancer Research 2015;21(23):5404-5405 DOI: 10.1158/1078/04332.CCR-15-2513
Gaston SM, Soares MA, Siddiqui MM, Vu D, Lee JM, Goldner DL, Brice MJ, Shih JC, Upton MP, Perides G, Baptista J, Lavin PT, Bloch BN, Genega EM, Rubin MA, Lenkinski RE. Tissue-print and print-phoresis as platform technologies for the molecular analysis of human surgical specimens: mapping tumor invasion of the prostate capsule. Nature Medicine 2004;11:95-101. 26 December 2004; doi:10.1038/nm1169
Citation Format: William E. Grizzle. Reduced Availability for Research of Human Tissues from Minority Populations. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA24.
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