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.
Background Three genes clustered together on chromosome 12 comprise a group of hydroxycarboxylic acid receptors (HCARs): HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently, HCARs have been functionally associated with breast cancer proliferation/survival; HCAR2 has been described as a tumor suppressor and HCAR1 and HCAR3 as oncogenes. Thus, we sought to identify germline variants in HCAR1, HCAR2, and HCAR3 that could potentially be associated with breast cancer risk. Methods Two different cohorts of breast cancer cases were investigated, the Alabama Hereditary Cancer Cohort and The Cancer Genome Atlas, which were analyzed through nested PCRs/Sanger sequencing and whole-exome sequencing, respectively. All datasets were screened for rare, non-synonymous coding variants. Results Variants were identified in both breast cancer cohorts, some of which appeared to be associated with breast cancer BC risk, including HCAR1 c.58C > G (p.P20A), HCAR2 c.424C > T (p.R142W), HCAR2 c.517_518delinsAC (p.G173T), HCAR2 c.1036A > G (p.M346V), HCAR2 c.1086_1090del (p.P363Nfs*26), HCAR3 c.560G > A (p.R187Q), and HCAR3 c.1117delC (p.Q373Kfs*82). Additionally, HCAR2 c.515C > T (p.S172L), a previously identified loss-of-function variant, was identified. Conclusions Due to the important role of HCARs in breast cancer, it is vital to understand how these genetic variants play a role in breast cancer risk and proliferation and their consequences on treatment strategies. Additional studies will be needed to validate these findings. Nevertheless, the identification of these potentially pathogenic variants supports the need to investigate their functional consequences.
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.
Background: Gastrointestinal stromal tumors are rare in pregnancy, and typically present in the second trimester with sizegreater-than-dates, abdominal pain, or nonspecific symptoms.Case: A 31-year-old gravida 1 female presented in the postpartum period with weight loss, cachexia, an abdominal mass, and persistent unexplained tachycardia. She was found to have a recurrent metastatic gastrointestinal stromal tumor and pulmonary emboli. She was anticoagulated and treated with neoadjuvant imatinib therapy with excellent initial response. Unfortunately, she died one year later due to complications of her disease and treatment. Conclusion:Malignancy should be considered in a pregnant woman with size-greater-than-dates or with an abdominal mass, especially when associated with unexplained weight loss and a history of a gastrointestinal stromal tumor, as the recurrence rate is high without continued maintenance therapy. Delivery at 35 to 37 weeks is recommended, and involvement of a multidisciplinary team improves outcomes.
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