Exploring biorepository donation patterns, experiences, and recommendations: a mixed-methods study among Appalachian adults enrolled in a sugary drink reduction program.

Background: Under-represented subgroups in biomarker research linked to behavioral health trials may impact the promise of precision health. This mixed methods study examines biorepository donations across an Appalachian sample enrolled in a sugary drink reduction intervention trial. Methods: Participants enrolled in the behavioral trial were asked to join an optional biomarker study and were tracked for enrollment and biospecimen returns (stool and/or buccal sample). At 6 months, participants completed a summative interview on decision-making process, experiences collecting samples, and recommendations to encourage biospecimen donation. Return rates were analyzed across demographics (i.e., age, gender, race, education, income, health literacy status, and rurality status) using chi-squares. Qualitative data were content coded with differences compared by biomarker study enrollment and donation choices. Results: Of the 249 invited participants, 171 (61%) enrolled, and 63% (n = 157) returned buccal samples and 49% (n = 122) returned stool samples. Metro residing participants were significantly more likely (56%) to return stool samples compared to non-metro (39%) counterparts [x2(1) = 6.61; p = 0.01]. Buccal sample return had a similar trend, 67 and 57%, respectively for metro vs. non-metro [x2(1) = 2.84; p = 0.09]. An additional trend indicated that older (≥40 years) participants were more likely (55%) to donate stool samples than younger (43%) participants [x2(1) = 3.39; p = 0.07]. No other demographics were significantly associated with biospecimen return. Qualitative data indicated that societal (66-81%) and personal (41-51%) benefits were the most reported reasons for deciding to donate one or both samples, whereas mistrust (3-11%) and negative perceptions of the collection process (44-71%) were cited the most by those who declined one or both samples. Clear instructions (60%) and simple collection kits (73%) were donation facilitators while challenges included difficult stool collection kits (16%) and inconveniently located FedEx centers (16%). Recommendations to encourage future biorepository donation were to clarify benefits to science and others (58%), provide commensurate incentives (25%), explain purpose (19%) and privacy protections (20%), and assure ease in sample collection (19%). Conclusion: Study findings suggest the need for biomarker research awareness campaigns. Researchers planning for future biomarker studies in medically underserved regions, like Appalachia, may be able to apply findings to optimize enrollment.

Potential role of fructose on human colon DNA methylation in racial disparities observed for colorectal cancer risk.

Background and aims: An increasing body of observational studies has linked fructose intake to colorectal cancer (CRC). African Americans (AAs) are significantly more likely than European Americans to consume greater quantities of fructose and to develop right-side colon cancer. Yet, a mechanistic link between these two associations remains poorly defined. We aimed to identify differentially methylated regions (DMRs) associated with dietary fructose consumption measures obtained from food frequency questionnaires in a cohort of normal colon biopsies derived from AA men and women (n=79). Methods: DNA methylation data from this study was obtained using the Illumina Infinium MethylationEPIC kit and is housed under accession GSE151732. DMR analysis was carried out using DMRcate in right and matched left colon, separately. Secondary analysis of CRC tumors was carried out using data derived from TCGA-COAD, GSE101764 and GSE193535. Differential expression analysis was carried out on CRC tumors from TCGA-COAD using DESeq2 . Results: We identified 4,263 right-side fructose-DMRs. In contrast, only 24 DMRs survived multiple testing corrections (FDR<0.05) in matched, left colon. To identify targets by which dietary fructose drives CRC risk, we overlaid these findings with data from three CRC tumor datasets. Remarkably, almost 50% of right-side fructose-DMRs overlapped regions associated with CRC in at least one of three datasets. TNXB and CDX2 ranked among the most significant fructose risk DMRs in right and left colon respectively that also displayed altered gene expression in CRC tumors. Conclusions: Our mechanistic data support the notion that fructose has a greater CRC-related effect in right than left AA colon, alluding to a potential role for fructose in contributing to racial disparities in CRC.