BackgroundHistorically, groups that are most susceptible to health and healthcare disparities have been underrepresented in medical research. It is imperative to explore approaches that can facilitate the recruitment of underrepresented individuals into research studies.MethodsTwo approaches, hospital and community‐based recruitment (CBR), were developed and implemented over 36 months to study the genetics of hereditary breast cancer and associated cancers in Alabama, a medically underserved state with double the national percentage of self‐identifying African Americans, establishing the Alabama Hereditary Cancer Cohort.ResultsOverall, 242 individuals enrolled. This included 84 cancer probands through hospital recruitment, as well as 76 probands and 82 family members through CBR. Eighty‐one percent of the study participants’ counties of residence are completely medically underserved. Furthermore, African Americans represent 26% of the hospital probands compared to 49% and 70% of the probands and family members who, respectively, enrolled through CBR.ConclusionAlthough both recruitment mechanisms were instrumental, the unique trust building, educational, and traveling components of CBR facilitated the enrollment of African Americans resulting in large families for genetic analyses. The ultimate goal is to gain insight from these rudimentary efforts in order to expand recruitment and accrue a unique resource for cancer genetics research.
Although an average woman in the United States can have a 12.5% lifetime risk of developing breast cancer (BC), inherited genetic risk variants can greatly influence a woman’s overall lifetime risk. Genes that harbor BC risk variants are referred to as BC susceptibility genes. Unfortunately, mutations in known BC susceptibility genes only explain approximately 35% of hereditary BC cases, leaving a large portion, approximately 65%, genetically unexplained. With the introduction of next-generation sequencing, several attempts have been carried out to identify additional hereditary BC susceptibility genes using whole-exome sequencing. The majority of these studies were relatively unsuccessful; however, Cybulski et al. (2015) successfully associated two rare truncation variants in RECQL, p.K555delinsMYKLIHYSFR and p.R215*, in a Polish and French-Canadian cohort, respectively. Subsequently, two additional studies were carried out in northern and southern regions of China, which also confirmed that overtly deleterious coding mutations in RECQL are associated with familial BC. Herein, we investigated RECQL variants in BC-affected African Americans (AAs) and European Americans (EAs). To our knowledge, this study represents the first attempt to identify an association between RECQL variants and BC cases in the United States. We initially screened all RECQL coding exons using polymerase chain reaction and Sanger sequencing in 49 BC cases (19 AAs and 30 EAs) from Alabama. Primarily synonymous variants were detected in both ethnicities; thus, in order to further investigate the role of RECQL synonymous variants in BC risk, we analyzed RECQL in blood-derived exomes of 168 and 580 BC-affected AAs and EAs, respectively, from The Cancer Genome Atlas (TCGA) project using an in-house bioinformatics pipeline. A case-control analysis revealed that all rare synonymous variants detected in EA BC cases were associated with BC, and p.S64= was significantly associated in both ethnicities. Interestingly, only one truncation variant was detected (p.Y492*) in all 748 BC cases analyzed. Unlike previous findings, this preliminary analysis suggests that rare RECQL synonymous variants may also increase an individual’s lifetime risk of developing BC; further investigation is warranted. Citation Format: Madison R. Chandler, Sydney Bergstresser, Anna LW Huskey, Elizabeth Stallworth, Amber Davis, Holly Dean, Brandon Johnson, Nancy D. Merner. Investigation of RECQL variants in European and African American breast cancer cohorts [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A29.
If there is any place to overcome research barriers it is Alabama. Known for being the site of one of the most unethical and inconceivable clinical studies - The Tuskegee Syphilis Study - and home of nearly double the national percentage of African Americans (AAs), history itself provides a substantial challenge. In Alabama, 85% of the counties are entirely medically underserved, most of which are rural, including the Alabama Black Belt, which is predominantly inhabited by AAs and associated with low economic status. Altogether, one can gather that getting proximate requires dedication, and considering all of the reported AA cancer health disparities, it is vital to address these barriers. Aiming to study hereditary breast cancer (BC) and other associated cancers in Alabama, we had to be adaptable and develop recruitment strategies appropriate for the community. In a recent publication, we described our initial efforts that were effective for recruiting AAs into the Alabama Hereditary Cancer Cohort (AHCC). A number of facets were key to this success, which included establishing community partners, educating and building trust in the community, and utilizing a recruitment bus, called the Gene Machine. As AA BC susceptibility is widely understudied, we realize the need to continue this effort; however, we recently went back to the drawing board and revamped our recruitment protocol in order to maximize our time and efficiency. We currently have over 150 AAs in the study and plan to bolster recruitment by implementing the protocol modifications. Ultimately, the goal of these rigorous efforts is to add to the limited, existing resources, i.e. biospecimens and genetic data, needed to better understand the science of cancer health disparities. When cancer-affected individuals enroll into our study, we carry out gene panel screening, initially searching for clinically significant variants in cancer susceptibility genes. Though our screening is currently research-based, through the development of our protocols, we felt it was important to offer the option to receive genetic research reports during the consent process. We had anticipated that many of our study participants would not have access to the care that provides such knowledge, and we have since confirmed that only ~20% of the cancer-affected AAs in the AHCC had previous clinical genetic screening. It was evident that most of those participants wanted such information with only 2% declining to be informed of the research results. Realizing that access to care is very limited in Alabama, we also established a collaborative telegenetic counseling project to provide services to mutation carriers in their local county health departments. Coupled together, these efforts attempt to provide study participants with a better understanding of disease risk and management, and allow integral genetic research to be carried out as we work towards reducing cancer health disparities. If there is any place to overcome barriers, it is here in Alabama and it is happening. Citation Format: Nancy Merner, Elizabeth Stallworth, Madison Bishop, Sophonie Omeler-Fenaud, Isaac McNeely, Anna Huskey. Getting proximate: Facing the truth about African American hereditary breast cancer research – insight from Alabama [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B043.
Breast cancer (BC) is a very serious health concern being the second most commonly diagnosed cancer among American women. Although the overall incidence rate of BC in African American (AA) and European American women converged in 2012, AA women are reported to have a higher mortality rate at every age, and a higher incidence rate under the age of 45, which is a hallmark of hereditary BC. Characteristics of hereditary BC include a family history of the disease, early ages of onset, bilateral BC, male BC, as well as the occurrence of other associated cancers such as ovarian and prostate. Cancer incidences in these families are influenced by inherited risk factors; currently, mutations in known susceptibility genes, including BRCA1/2, explain ~20-30% of hereditary cases, leaving up to ~70% genetically unsolved. Despite the universal need to decipher the currently unexplained cases, it is important to note that these statistics are mainly the result of studying individuals of European descent. The mutational landscape that explains AA hereditary BC is more obscure since, comparatively, it has been vastly understudied. Recognizing this knowledge gap, our group is committed to adding to the current limited resources necessary to better understand AA BC genetics. We are doing this through a strategic community-based recruitment protocol to enroll underrepresented individuals in Alabama, adding to the Alabama Hereditary Cancer Cohort. With over 150 AAs enrolled to date, we have ascertained some impressive AA BC families. Of those families, Family 1CAD is one of the largest with over 15 family members enrolled. Their participation was fostered through an invitation to their family reunion. There, it was disclosed that a deceased family member had a pathogenic BRCA1 mutation (p.M1796R). Therefore, all participating family members were first screened for the BRCA1 mutation through polymerase chain reactions and Sanger sequencing; interestingly, not all cancer-affected individuals screened positive for this mutation. Therefore, five cancer-affected individuals (three mutation-positive and two mutation-negative) were selected and screened using an exploratory research-based gene panel that targets genes that have been suggested, predicted, or clinically proven to be associated with BC and associated cancers. Firstly, this screening confirmed each individual’s mutation status. It also provided additional insight; for example, all three cancer-affected individuals who have BRCA1 M1796R also share a truncation variant in a candidate gene on the panel, which plays an important role in cell cycle regulation (GeneX). A preliminary analysis using AA BC cases from The Cancer Genome Atlas and ethnic-specific controls from the Exome Variant Server, suggests that truncation variants in GeneX are associated with AA BC risk. We are in the process of validating these findings and determining how this truncation variant modifies risk in BRCA1 mutation carriers. Citation Format: Sophonie Omeler-Fenaud, Madison Bishop, Elizabeth Stallworth, Isaac McNeely, Nancy Merner. Complexities of hereditary breast cancer: Investigating a large African American family [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C041.
Our group has established the Alabama Hereditary Cancer Cohort and primarily investigates breast cancer genetics in African American, an underrepresented group in biomedical research. Alabama has double the national percentage of African Americans and is the location of the infamous and unethical Tuskegee Syphilis Study. Therefore, strategic protocols were developed to break research participation barriers, effectively recruiting African American hereditary breast cancer cases and families. Our initial recruitment strategies involved both hospital-based and community-based recruitment; the latter involved our recruitment bus, the Gene Machine, and focused on African American engagement. Since our initial publication, our community-based recruitment protocol has been modified. Many of the modifications were due to the pandemic, limiting in-person community engagement. In-person education seminars and enrollment sessions transitioned to virtual meetings, using various video-conferencing platforms. Regarding virtual enrollments, upon agreement to proceed with the virtual consent process, study participants are mailed an enrollment kit containing study consent forms, saliva collection kits, return mailing materials, and instructions. Once received, an enrollment appointment is made, and the consent process follows the procedure for in-person study enrollment, concluding with the saliva sample collection. Once collected, the sample is packaged with the consent forms and returned to our laboratory in the postage-paid mailer. Community-based recruitment has also been enhanced by partnering with the Alabama Department of Public Health to identify study participants through the Alabama Statewide Cancer Registry, similar to the very successful Carolina Breast Cancer Study. Furthermore, Research Champions have been added to the protocol, defined as primary healthcare providers and specialists who aid in recruitment by identifying individuals who fit the study criteria. The concept of Research Champions was developed after recognizing that the requirements to execute hospital-based recruitment are arduous on partnering hospitals. Thus, the sole function of a Research Champion is identifying prospective study participants, relieving the burden on physicians and hospital staff. Lastly, our Gene Machine Facebook page and newly designed website, tailored towards laypeople/study participants, facilitate additional engagement through ads, videos, and photos. Ultimately, these processes reduce the travel burden, aid in social distancing, and expand our reach, enhancing recruitment and enrollment efforts and breaking barriers to African American research. Citation Format: Nancy Merner, Elizabeth Stallworth, Erica Reasor, Katia Khoury, Lily Gutnik, Meagan Farmer, Brandon Johnson. The Alabama Hereditary Cancer Cohort – New strategies for African American recruitment [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B088.
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