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BACKGROUND: It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D-binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear. METHODS: We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression. RESULTS: In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P = .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (Pinteraction = .003). CONCLUSIONS: Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma-specifically from thicker, higher-risk melanoma-than individuals without this Gc1f haplotype.

MDM2-SNP309 (rs2279744), a common genetic modifier of cancer incidence in Li-Fraumeni syndrome, modifies risk, age of onset, or prognosis in a variety of cancers. Melanoma incidence and outcomes vary by sex, and although SNP309 exerts an effect on the estrogen receptor, no consensus exists on its effect on melanoma. MDM2 and MDM4 restrain p53-mediated tumor suppression, independently or together. We investigated SNP309, an a priori MDM4-rs4245739, and two coinherited variants, in a population-based cohort of 3663 primary incident melanomas. Per-allele and per-haplotype (MDM2_SNP309-SNP285; MDM4_rs4245739-rs1563828) odds ratios (OR) for multiple-melanoma were estimated with logistic regression models. Hazard ratios (HR) for melanoma death were estimated with Cox proportional hazards models. In analyses adjusted for covariates, females carrying MDM4-rs4245739*C were more likely to develop multiple melanomas (ORper-allele = 1.25, 95% CI 1.03-1.51, and Ptrend = 0.03), while MDM2-rs2279744*G was inversely associated with melanoma-death (HRper-allele = 0.63, 95% CI 0.42-0.95, and Ptrend = 0.03). We identified 16 coinherited expression quantitative loci that control the expression of MDM2, MDM4, and other genes in the skin, brain, and lungs. Our results suggest that MDM4/MDM2 variants are associated with the development of subsequent primaries and with the death of melanoma in a sex-dependent manner. Further investigations of the complex MDM2/MDM4 motif, and its contribution to the tumor microenvironment and observed associations, are warranted.

BackgroundGenome-wide association studies have reported that genetic variation at ANRIL (CDKN2B-AS1) is associated with risk of several chronic diseases including coronary artery disease, coronary artery calcification, myocardial infarction, and type 2 diabetes mellitus. ANRIL is located at the CDKN2A/B locus, which encodes multiple melanoma tumor suppressors. We investigated the association of these variants with melanoma prognostic characteristics.MethodsThe Genes, Environment, and Melanoma Study enrolled 3,285 European origin participants with incident invasive primary melanoma. For each of ten disease-associated SNPs at or near ANRIL, we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and ORs for presence of ulceration and tumor-infiltrating lymphocytes (TIL). We also assessed effect modification by tumor NRAS/BRAF mutational status.ResultsRs518394, rs10965215, and rs564398 passed false discovery and were each associated (P ≤ 0.005) with TILs, although only rs564398 was independently associated (P = 0.0005) with TILs. Stratified by NRAS/BRAF mutational status, rs564398*A was significantly positively associated with TILs among NRAS/BRAF mutant, but not wild-type, cases. We did not find SNP associations with Breslow thickness or ulceration.ConclusionsANRIL rs564398 was associated with TIL presence in primary melanomas, and this association may be limited to NRAS/BRAF-mutant cases.ImpactPathways related to ANRIL variants warrant exploration in relationship to TILs in melanoma, especially given the impact of TILs on immunotherapy and survival.

This article discusses a feasibility study on the use of mobile teledermoscopy for monitoring high-risk melanoma patients. The study involved 75 patients from two Australian tertiary centers who used a portable teledermoscope compatible with their mobile phones. The study found that mobile teledermoscopy was effective in detecting skin cancers, with the potential to fast-track 37% of visits for concerning lesions. Participants aged ≤40 years and those with tertiary education provided more reliable transmissions. The study also noted a small additional cost to the healthcare system. The authors of a letter to the editor discuss the study and suggest that mobile teledermoscopy can be used to support conventional practice for high-risk patients under certain criteria. The study was supported by the NHMRC Centre of Research Excellence in Melanoma and the Melanoma Institute of Australia. [Extracted from the article]

This scoping review aims to systematically gather evidence from personalized cancer-screening studies across various cancers, summarize key components and outcomes, and provide implications for a future personalized melanoma-screening strategy. Peer-reviewed articles and clinical trial databases were searched for, with restrictions on language and publication date. Sixteen distinct studies were identified and included in this review. The studies' results were synthesized according to key components, including risk assessment, risk thresholds, screening pathways, and primary outcomes of interest. Studies most frequently reported about breast cancers (n = 7), followed by colorectal (n = 5), prostate (n = 2), lung (n = 1), and ovarian cancers (n = 1). The identified screening programs were evaluated predominately in Europe (n = 6) and North America (n = 4). The studies employed multiple different risk assessment tools, screening schedules, and outcome measurements, with few consistent approaches identified across the studies. The benefit–harm assessment of each proposed personalized screening program indicated that the majority were feasible and effective. The establishment of a personalized screening program is complex, but results of the reviewed studies indicate that it is feasible, can improve participation rates, and screening outcomes. While the review primarily examines screening programs for cancers other than melanoma, the insights can be used to inform the development of a personalized melanoma screening strategy. [ABSTRACT FROM AUTHOR]

Objectives: Skin cancer is highly preventable through primary prevention activities such as avoiding ultraviolet radiation exposure during peak times and regular use of sun protection. General practitioners (GPs) and primary care nurses have key responsibilities in promoting sustained primary prevention behaviour. We aimed to review the evidence on skin cancer primary prevention activities in primary care settings, including evidence on feasibility, effectiveness, barriers and enablers. Study type: Rapid review and narrative synthesis. Methods: We searched published literature from January 2011 to October 2022 in Embase, Medline, PsychInfo, Scopus, Cochrane Central and CINAHL. The search was limited to skin cancer primary prevention activities within primary care settings, for studies or programs conducted in Australia or countries with comparable health systems. Analysis of barriers and enablers was informed by an implementation science framework. Results: A total of 31 peer-reviewed journal articles were included in the review. We identified four main primary prevention activities: education and training programs for GPs; behavioural counselling on prevention; the use of novel risk assessment tools and provision of risk-tailored prevention strategies; and new technologies to support early detection that have accompanying primary prevention advice. Enablers to delivering skin cancer primary prevention in primary care included pairing preventive activities with early detection activities, and access to patient resources and programs that fit with existing workflows and systems. Barriers included unclear requirements for skin cancer prevention counselling, competing demandswithin the consultation and limited access to primary care services, especially in regional and remote areas. Conclusions: These findings highlight potential opportunities for improving skin cancer prevention activities in primary care. Ensuring ease of program delivery, integration with early detection and availability of resources such as risk assessment tools are enablers to encourage and increase uptake of primary prevention behaviours in primary care, for both practitioners and patients. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence of melanoma in Australia, highlighting the need for evidence-based approaches to skin cancer detection. It emphasizes the importance of organized screening programs to improve early detection and reduce mortality rates. The text also addresses the challenges of accurate melanoma screening, the use of diagnostic technologies, and the necessity of tailored screening intervals based on individual risk factors. Additionally, it calls for increased investment in education, workforce upskilling, and equitable access to quality skin checks to enhance skin cancer prevention and detection. [Extracted from the article]

Background: Full‐body skin examination (FSE) is a vital practice in the diagnosis of cutaneous malignancy. Precisely how FSE should be conducted with respect to concealed site inclusion remains poorly elucidated. Objective: To establish the approach of Australian dermatologists to concealed site examination (CSE). Methods: A cross‐sectional study was performed consisting of an online self‐administered 11‐question survey delivered to fellows of the Australasian College of Dermatologists. Results: There were 237 respondents. Anogenitalia was the least often examined concealed site (4.6%), and 59.9, 32.9, and 14.3% reported always examining the scalp, breasts, and oral mucosa, respectively. Patient concern was the most frequently cited factor prompting examination, while many cited low incidence of pathology and limited chaperone availability as the main barriers to routine examination of these sites. Conclusion: Most Australian dermatologists do not routinely examine breasts, oral mucosal, or anogenital sites as part of an FSE. Emphasis should be made on identifying individual patient risk factors and education regarding self‐examination of sensitive sites. A consensus approach to the conduct of the FSE, including concealed sites, is needed to better delineate clinician responsibilities and address medicolegal implications. [ABSTRACT FROM AUTHOR]

Background: Cancer screening that is tailored to individual risk has the potential to improve health outcomes and reduce screening-related harms, if implemented well. However, successful implementation depends on acceptability, particularly as this approach will require GPs to change their practice. Aim: To explore Australian GPs' views about the acceptability of risk-tailored screening across cancer types and to identify barriers to and facilitators of implementation. Design and setting: A qualitative study using semi-structured interviews with Australian GPs. Method: Interviews were carried out with GPs and audio-recorded and transcribed. Data were first analysed inductively then deductively using an implementation framework. Results: Participants (n = 20) found risk-tailored screening to be acceptable in principle, recognising potential benefits in offering enhanced screening to those at highest risk. However, they had significant concerns that changes in screening advice could potentially cause confusion. They also reported that a reduced screening frequency or exclusion from a screening programme for those deemed low risk may not initially be acceptable, especially for common cancers with minimally invasive screening. Other reservations about implementing risk-tailored screening in general practice included a lack of high-quality evidence of benefit, fear of missing the signs or symptoms of a patient's cancer, and inadequate time with patients. While no single preferred approach to professional education was identified, education around communicating screening results and risk stratification was considered important. Conclusion: GPs may not currently be convinced of the net benefits of risk-tailored screening. Development of accessible evidence-based guidelines, professional education, risk calculators, and targeted public messages will increase its feasibility in general practice. [ABSTRACT FROM AUTHOR]

Background Compared with the general population, people with a previous melanoma are at increased risk of developing another primary melanoma. Understanding the risk factors associated with multiple primary melanomas can inform patient education and tailored surveillance. Objectives To examine the risk factors for subsequent primary melanoma in people with a previous melanoma, by conducting a systematic review and meta-analysis of the available data. Methods A systematic literature search was conducted in CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase and MEDLINE. Studies that reported a risk estimate or raw frequencies and conducted between 1982 and August 2022 were included. Adjusted risk estimates were prioritized over univariable risk estimates. PRISMA reporting guidelines were followed. Random effects meta-analysis was conducted to derive pooled estimates. Quality assessment was conducted by two researchers using the Newcastle-Ottawa scale. GRADE was used to rate the certainty and quality of the evidence. Results Data from 27 studies involving 413 181 participants were pooled and analysed. Risk factors assessed included age and sex, environmental, lifestyle, phenotypic, genetic and histopathological factors, and there was wide variation in how they were categorized and analysed. Independent risk factors identified from pooled analyses included male sex [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.40–1.53], increasing age per 10 years (HR 1.19, 95% CI 1.14–1.24), light skin colour (HR 1.44, 95% CI 1.23–1.70), family history [odds ratio (OR) 1.79, 95% CI 1.25–2.56], CDKN2A mutation (OR 5.29, 95% CI 2.70–10.37), a high or moderate naevus count [OR 2.63 (95% CI 1.61–4.30) and OR 1.64 (95% CI 1.07–2.51), respectively], one or more atypical naevi (OR 3.01, 95% CI 1.52–5.97), first lesions occurring on the head or neck, lentigo maligna subtype (HR 1.16, 95% CI 1.15–1.17), other subtype (HR 1.14, 95% CI 1.03–1.27) and inadequate sun protection (HR 1.85, 95% CI 0.98–3.50). Based on the GRADE criteria, there was high to very low confidence in the pooled effect estimates. Conclusions This meta-analysis identified several consistent, independent risk factors for the development of subsequent primary melanoma. These findings will help stratify the risk of subsequent melanoma, tailor skin-check schedules and inform patient education. [ABSTRACT FROM AUTHOR]