Background
Consumer engagement is increasingly recognized as an instrumental component of health research, with many institutions and international bodies mandating it as part of the research and ...funding process. Given an increasing utilization of consumer engagement in health research, it is critical to identify the literature which support its value and tools that capture successful outcomes. To develop an overview of the literature, we conducted an umbrella scoping review exploring important outcomes of consumer engagement in health research combined with a scoping review of relevant frameworks. Specifically, we aimed to capture outcomes which reflect authentic and meaningful consumer engagement.
Methods
Four databases (PubMed, Embase, CINAHL and Cochrane Library) were searched using key search terms. Records were included if they were review articles or frameworks that addressed outcomes of consumer engagement in health research. Data was analyzed using descriptive statistics and an inductive qualitative content analysis. Identified outcomes were sorted based on the three most relevant stakeholder groups (consumer, researcher, institution).
Results
A total of twenty articles that explored a variety of health disciplines were included. We identified fifteen measurable outcomes of consumer engagement in health research. Eight core outcomes were relevant to all stakeholder groups, and were considered fundamental to authentic consumer engagement including (1) trust, (2) empowerment, (3) respect, (4) confidence in the outcomes of the research, (5) transparency of the research process, (6) satisfaction with the consumer engagement program, (7) knowledge and experiences of consumers, and (8) degree of consumer engagement. Outcomes pertaining to specific stakeholder groups included representativeness and diversity of the consumer groups, research relevance to consumers, funding opportunities, quality/validity of the research, recruitment/retention rates, translation and dissemination of research, and interpretation of results.
Conclusion
This review identified key measurable outcomes that could be captured when evaluating the impacts of consumer engagement on health research and the success of consumer engagement programs. All outcomes identified were relatively underexplored within the literature, and inadequately and/or inconsistently evaluated amongst studies. Future research should consult all stakeholder groups to identify outcomes perceived to be reflective of optimal consumer engagement.
While ultraviolet radiation is a known risk factor, twin studies have shown that 58% of melanoma risk is heritable.2 Specifically, 10% of melanoma cases have a positive family history and 1% are ...diagnosed with familial melanoma (≥3 melanoma-affected individuals who are first and/or second relatives).3 4 Between 20% and 40% of familial melanoma cases carry a pathogenic/likely pathogenic germline variant in a high-penetrance melanoma gene (CDKN2A, CDK4, BAP1, TERT, TERF2IP, POT1, ACD, POLE).4 5 CDKN2A is the primary high-risk gene for familial melanoma, accounting for ~90% of mutation-positive cases.4 Genome-wide association studies and candidate gene studies have also revealed moderate melanoma susceptibility loci and variants (MC1R, MITF, EBF3, NEK11, GOLM1).3 4 Golgi-phosphoprotein-2/Golgi-membrane-protein-GP73 (GOLM1) encodes a Golgi transmembrane protein localised in epithelial lineage cells. Specifically, the highly conserved 56aa-152aa region is critical for GOLM1 dimerisation.6 One study discovered inhibiting GOLM1 expression resulted in upregulation of epithelial-mesenchymal transition promoting migration and invasion of cancer cells.7 In addition, increased GOLM1 protein expression has been shown to drive oncogenesis in melanoma cell lineages, with increased tumour thickness, ulceration and higher rates of metastasis reported.8 A GOLM1 non-synonymous variant (p.S307L) has been reported to segregate with autosomal dominant cutaneous melanoma across three generations in one family.1 Furthermore, the same study showed an increased frequency of the p.S307L in melanoma cases as compared with controls.1 When reporting GOLM1 p.S307L, Teerlink et al hypothesised that the p.S307L impacts the p.S308 phosphorylation site thereby adversely affecting protein–protein interactions.1 However, there has been no functional validation of the p.S307L variant or reporting of any other GOLM1 variants to date. In this study, whole-exome sequencing was performed on a cohort of 384 unrelated individuals previously diagnosed with primary melanoma: n=230 multiple primary melanoma (MPM) and n=154 single primary melanoma (SPM).9 After excluding individuals positive for pathogenic variants in high-penetrance melanoma genes (CDKN2A, CDK4, BAP1, TERF2IP, POT1, ACD, POLE), exome data were filtered to identify rare (minor allele frequency (MAF) <0.005) variants in GOLM1 which were predicted to alter protein function using in-silico prediction tools.10 Eleven individuals carried five missense GOLM1 variants (2.9%) (table 1). None of these were previously reported in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) in association with disease.Table 1 Rare/novel variants of interest in GOLM1 (n=5) identified in 11 of 384 high-risk individuals diagnosed with single or multiple primary melanoma ID Variant MAF VarSome Number of melanomas 70509 c.C920T (p.S307L) 0.003 Benign SPM (>40 years) 70510 MPM (>40 years) 70511 SPM (<40 years) 70512 SPM (<40 years) 70513 SPM (<40 years) 70514 SPM (<40 years) 70515 SPM (<40 years) 70516 c.G518A (p.R173Q) 0.000003 LB MPM (<40 years) 70517 MPM (>40 years) 70518 c.G412A (p.V138I) 0.00004 LB MPM (>40 years) c.G991A (p.E331K) 0.000003 LB 70519 c.A266G (p.N89S) 0.00005 LB SPM (<40 years) LB, likely benign; MAF, minor allele frequency; MPM, multiple primary melanoma; SPM, single primary melanoma.
Human research ethics committees (HRECs) are evaluating increasing quantities of genomic research applications with complex ethical considerations. Genomic confidence is reportedly low amongst many ...non-genetics-experts; however, no studies have evaluated genomic confidence levels in HREC members specifically. This study used online surveys to explore genomic confidence levels, predictors of confidence, and genomics resource needs of members from 185 HRECs across Australia. Surveys were fully or partially completed by 145 members. All reported having postgraduate 94 (86%) and/or bachelor 15 (14%) degrees. Participants consisted mainly of researchers (n = 45, 33%) and lay members (n = 41, 30%), affiliated with either public health services (n = 73, 51%) or public universities (n = 31, 22%). Over half had served their HREC Formula: see text3 years. Fifty (44%) reviewed genomic studies Formula: see text3 times annually. Seventy (60%) had undertaken some form of genomic education. While most (94/103, 91%) had high genomic literacy based on familiarity with genomic terms, average genomic confidence scores (GCS) were moderate (5.7/10, n = 119). Simple linear regression showed that GCS was positively associated with years of HREC service, frequency of reviewing genomic applications, undertaking self-reported genomic education, and familiarity with genomic terms (p < 0.05 for all). Conversely, lay members and/or those relying on others when reviewing genomic studies had lower GCSs (p < 0.05 for both). Most members (n = 83, 76%) agreed further resources would be valuable when reviewing genomic research applications, and online courses and printed materials were preferred. In conclusion, even well-educated HREC members familiar with genomic terms lack genomic confidence, which could be enhanced with additional genomic education and/or resources.
MITF E318K moderates melanoma risk. Only five MITF E318K homozygous cases have been reported to date, one in association with melanoma. This novel report uses 3D total‐body‐photography (TBP) to ...describe the dermatological phenotype of a homozygous MITF E318K individual. The case, a 32‐year‐old male, was diagnosed with his first of six primary melanomas at 26 years of age. Five melanomas were located on the back and one in the groin. Two were superficial spreading. Three arose from pre‐existing naevi and one was a rare naevoid melanoma. 3D‐TBP revealed a high naevus count (n = 162) with pigmentation varying from light to dark. Most naevi generally (n = 90), and large (>5 mm diameter) and clinically atypical naevi specifically were located on the back where sun damage was mild. In contrast, naevi count was low (n = 25 total) on the head/neck and lower limbs where sun damage was severe. Thus, melanoma location correlated with naevi density, rather than degree of sun damage. In addition to the MITF E318K homozygosity, there was heterozygosity for four other moderate‐risk variants, which may contribute to melanoma risk. Further research is warranted to explore whether melanomas in E318K heterozygous and other homozygotes coincide with regions of high naevi density as opposed to sun damage. This could inform future melanoma screening/surveillance.
Melanomas occuring in regions of high naevus density in MITF E318K Homozygous individual.
This study aimed to systematically review current models for communicating polygenic scores (PGS) and psycho-behavioral outcomes of receiving PGSs.
Original research on communicating PGSs and ...reporting on psycho-behavioral outcomes was included. Search terms were applied to 5 databases and were limited by date (2009-2021).
In total, 28 articles, representing 17 studies in several disease settings were identified. There was limited consistency in PGS communication and evaluation/reporting of outcomes. Most studies (n = 14) presented risk in multiple ways (ie, numerically, verbally, and/or visually). Three studies provided personalized lifestyle advice and additional resources. Only 1 of 17 studies reported using behavior change theory to inform their PGS intervention. A total of 8 studies found no evidence of long-term negative psychosocial effects up to 12 months post result. Of 14 studies reporting on behavior, 9 found at least 1 favorable change after PGS receipt. When stratified by risk, 7 out of 9 studies found high PGS was associated with favorable changes including lifestyle, medication, and screening. Low-risk PGS was not associated with maladaptive behaviors (n = 4).
PGS has the potential to benefit health behavior. High variability among studies emphasizes the need for developing standardized guidelines for communicating PGSs and evaluating psycho-behavioral outcomes. Our findings call for development of best communication practices and evidence-based interventions informed by behavior change theories.
Oculocutaneous albinism (OCA) is a rare condition characterized by hypopigmentation. A female proband and her sister, both with primary amelanotic/hypopigmented melanoma, underwent three-dimensional ...total-body photography and dermoscopy. Both sisters had exome sequencing along with their brother, who had OCA but no history of melanoma. Imaging analysis was consistent with OCA in terms of individual typology angle scores, degree of sun damage, and high naevus counts. Exome data filtered for variants in known OCA and melanoma/naevi susceptibility genes (n = 98) found all siblings were compound heterozygous for TYR mutations (Arg402Ter and Val275Phe), previously reported as causative OCA variants. A rare missense variant in PARP1 (p.Pro377Ser) was solely present in the melanoma-unaffected brother, which is noteworthy as this was previously reported as potentially protective in a familial melanoma pedigree positive for CDKN2A mutations. Evaluation and confirmation of functional impact in larger cohorts could personalize melanoma screening in OCA.
Background:
Melanoma genetic testing reportedly increases preventative behaviour without causing psychological harm. Genetic testing for familial melanoma risk is now available, yet little is known ...about dermatologists’ perceptions regarding the utility of testing and genetic testing ordering behaviours.
Objectives:
To survey Australasian Dermatologists on the perceived utility of genetic testing, current use in practice, as well as their confidence and preferences for the delivery of genomics education.
Methods:
A 37-item survey, based on previously validated instruments, was sent to accredited members of the Australasian College of Dermatologists in March 2021. Quantitative items were analysed statistically, with one open-ended question analysed qualitatively.
Results:
The response rate was 56% (256/461), with 60% (153/253) of respondents between 11 and 30 years post-graduation. While 44% (112/252) of respondents agreed, or strongly agreed, that genetic testing was relevant to their practice today, relevance to future practice was reported significantly higher at 84% (212/251) (
t =
-9.82,
p
< 0.001). Ninety three percent (235/254) of respondents reported rarely or never ordering genetic testing. Dermatologists who viewed genetic testing as relevant to current practice were more likely to have discussed (
p
< 0.001) and/or offered testing (
p
< 0.001). Respondents indicated high confidence in discussing family history of melanoma, but lower confidence in ordering genetic tests and interpreting results. Eighty four percent (207/247) believed that genetic testing could negatively impact life insurance, while only 26% (63/244) were aware of the moratorium on using genetic test results in underwriting in Australia. A minority (22%, 55/254) reported prior continuing education in genetics. Face-to-face courses were the preferred learning modality for upskilling.
Conclusion:
Australian Dermatologists widely recognise the relevance of genetic testing to future practice, yet few currently order genetic tests. Future educational interventions could focus on how to order appropriate genetic tests and interpret results, as well as potential implications on insurance.
Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair ...colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored.
To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K- individuals.
Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank).
The cohort comprised 1165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P < 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P < 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele odds ratio (OR) 2.04 (95% confidence interval 1.67-2.49); P = 0.01, while the r allele risk was comparable with the wt allele OR 0.78 (0.54-1.14) vs. 1.00, respectively. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt OR 0.52 (0.20-1.38). Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P < 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals.
RHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.
As genetic testing becomes increasingly utilized in health care, consumer awareness and understanding is critical. Both are reported to be low in Australia, though there are limited studies to date. ...A consumer survey assessed perceived knowledge, awareness and attitudes toward genetic medicine, prior to consumers’ genomics forums in Queensland in 2018 and 2019. Data was analyzed using
t
-test and Mann-Whitney
U
tests analysis to detect any associations between sociodemographic factors and familiarity or attitudes. This highly educated and experienced health consumer cohort reported they were significantly more familiar with the healthcare system generally than genetic medicine specifically (
p
< 0.0001). Consumers perceived that genetic testing would be significantly more important in the future than it is currently (
p
< 0.00001). Consumers agreed that genetic testing should be promoted (91.4%), made available (100%), better funded (94.2%), and offered to all pregnant women (81.6%). The preferred learning modality about genetics was internet sites (62.7%) followed by talks/presentations (30.8%). Benefits of genetic testing, reported in qualitative responses, included the potential for additional information to promote personal control and improve healthcare. Perceived concerns included ethical implications (including privacy and discrimination), and current limitations of science, knowledge and/or practice. This study demonstrates that even knowledgeable consumers have little familiarity with genetic medicine but are optimistic about its potential benefits. Ethical concerns, particularly concerns regarding genetic discrimination should inform legislation and policy. Consumers are supportive of online resources in increasing genomic literacy.
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