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.
Over 60% of the Alabama population is medically underserved, including the entire population of many Alabama counties. These counties are generally rural and have transportation barriers, thus a lack of access to healthcare results in poor cancer outcomes. These healthcare gaps, in addition to lower education levels and mistrust towards researcher/healthcare providers, highlight the challenges but also the need to make a difference in this underserved and understudied population. In general, recruitment for human genetic research studies presents major challenges, and, despite federal mandates to include women and minorities in federally funded research, African Americans (AAs) remain underrepresented in cancer genetic research. Recruitment of participants requires extensive efforts and strategic planning in order to overcome the difficulties, such as distrust towards medical research and logistical challenges of recruiting under-served and under-represented individuals. These considerations led to the establishment of two IRB-approved protocols, hospital recruitment (#14-232) and community-based recruitment (CBR; #15-111) to recruit cancer individuals/families from Alabama and identify genetic risk factors. Hospital recruitment was established through a partnership with East Alabama Medical Center (EAMC), and CBR targets medically underserved individuals through a mechanism aimed to educate and build trust in the community. Through connections fostered by community-partners, CBR team members travel to rural communities all over Alabama to be introduced to, educate, and recruit patients/survivors and their family members. All CBR team members are phlebotomy trained. Recruitment particularly focuses on cancer associated with Hereditary Breast and Ovarian Cancer (HBOC) Syndrome since there are two disparities within the AA population that may be genetically linked. Firstly, AA women are generally diagnosed with a more aggressive and less treatable breast cancer (BC) sub-type and have a higher incidence rate of BC under the age of 40 compared to Caucasians. Secondly, AA males are generally diagnosed with prostate cancer (PC) at a younger age and with larger tumors compared to Caucasians. Considering that (1) an early age of onset is a hallmark of hereditary cancer, (2) hereditary BC is associated with an increased risk of ovarian cancer (OvC) and PC, and (3) the Black Women's Health Study has demonstrated there is a strong familial component of AA BC, inherited and potentially overlapping genetic risk factors may explain these disparities. Thus, the study enrollment criteria include individuals (1) diagnosed with BC, OvC, or PC under the age of 45 and/or (2) diagnosed with BC, OvC, or PC with have a cancer family history. Ultimately, in an effort to recruit informative families for genetic study, both cancer-affected and unaffected family members of study participants can join the study. To date, 133 DNA samples from 74 cancer families are stored in the Merner DNA Bank; 33 and 41 probands have been recruited through EAMC and CBR, respectively. CBR has been the most effective mechanism of AA BC recruitment (20/36) compared to hospital recruitment (5/32). Probands are screened for known and candidate susceptibility genes using the BRAP (BReast And Prostate) gene-screening panel. This aims to provide insight towards the true contribution of mutations in known susceptibility genes, and identify non-mutation individuals/families for novel HBOC susceptibility gene discovery efforts. Additionally, this study offers each participant the option to receive her/his confidential research-based gene screening results and aims to translate those results to the clinic by providing free UAB telegenetic counseling to underserved individuals through the use of telemedicine carts at equipped Alabama County Health Departments. Citation Format: Nancy Merner, Madison Chandler, Amber Davis, Ebony Jackson, Erin Bilgili, Cameron Turner, Kasey Shepp, Stephanie Spina, Brandon Johnson. Cancer genetics research in Alabama: Recruitment mechanisms to reach the underserved. [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 A47.
The cover image, by Madison R. Bishop et al., is based on the Original Article Establishment of the Alabama Hereditary Cancer Cohort ‐ strategies for the inclusion of underrepresented populations in cancer genetics research, DOI: 10.1002/mgg3.443. Image Credit: Nancy Merner, Principle Investigator – The Gene Machine.
African American (AA) women are diagnosed with breast cancer (BC) at a higher rate under the age of 40 compared to Caucasian women and are more often diagnosed with triple-negative (TN) BC, a less treatable and more aggressive BC sub-type. Since an early age of onset is a key characteristic of hereditary BC, genetic risk factors are likely contributing towards these BC disparities. Genes that harbor genetic risk variants are referred to as BC susceptibility genes. Prior to searching for novel BC susceptibility genes, previously identified BC susceptibility genes should initially be excluded. Since the introduction of next-generation sequencing, gene-screening panels have been implemented; this innovative approach involves designing probes for target-capture of genes of interest, amplification, and sequencing on a massively parallel array. AA BC genetics is understudied; however, recently, Churpek et al. published the first article to screen AA hereditary/early onset/TN BC cases for a panel of known BC susceptibility genes. This study identified 68 pathogenic germline mutations in 65 of 289 (22%) AA cases; 18% had a BRCA1 or BRCA2 mutation. The authors acknowledged the paucity of their study and that more gene panel screening studies are needed. Currently, it appears that the majority and spectrum of BC susceptibility genes/risk variants that contribute towards the disproportionate number of aggressive and young onset AA BCs remain to be identified. Our group has custom-designed an Agilent Technologies (AT) HaloPlex probe kit, named BRAP (BReast And Prostate) that targets 87 known and candidate BC and prostate cancer (PC) susceptibility genes using the AT SureDesign program. PC genes were included on the panel since AA males are frequently diagnosed with PC in BC families, more susceptible to PC compared to Caucasians, and normally diagnosed at a younger age with larger tumors. Furthermore, men carrying BRCA1/2 mutations have a higher risk of PC, so further genetic overlap will likely be detected through BRAP screening. Ultimately, the probes were designed to generate 100 base pair (bp) reads on an Illumina platform. All coding exons as well as the 5' and 3' untranslated regions of the 87 genes were targeted, totaling 499.5 kbp. The designed probes covered 98.9% of the targeted region. Forty-six seemingly unrelated individuals (24 AA and 22 Caucasians) from Alabama who were diagnosed with BC under the age of 45 and/or had a BC family history were selected for the initial BRAP capture; the HaloPlex HS Target Enrichment System For Illumina Sequencing Protocol (Version C0) was followed. Each individually prepared and indexed library was quantified using a Bioanalyzer 2100. The targeted DNA from 44 of the 46 individuals were successfully captured and amplified. The successful samples were pooled for sequencing; the sample was loaded onto one flow cell lane and run on an Illumina HiSeqTM 2500 at the HudsonAlpha Genomic Services Laboratory. The sequencing data was downloaded and is being processed using an in-house, bioinformatics pipeline. Two of the screened individuals served as positive controls since upon recruitment one reported a mutation in BRCA1 and the other a mutation in BRCA2. The pipeline has been optimized using the control with BRCA1 p.M1775R, which has been successfully identified. Variant calling files are being processed for the remaining screened individuals. This data provides great insight towards the array of mutations in known BC and PC susceptibility genes that contributes towards hereditary AA BC. Furthermore, non-mutation individuals/families identified through BRAP screening will be whole-genome sequenced in order to identify novel, BC susceptibility genes that may contribute towards disease disparity. Citation Format: Madison R. Chandler, Kasey J. Shepp, Stephanie M. Spina, Nancy D. Merner. A breast cancer susceptibility gene screening panel for variant discovery and gene exclusion in an African American cohort from Alabama. [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 B35.
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