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Skin phenotype, host genotype and ultraviolet (UV) damage play a role in the development of melanoma.To ascertain whether the level of UV damage at the site of melanomas was associated with genetic polymorphisms.Deep phenotyping was performed on 1244 individuals; 281 with multiple primary melanomas (MPMs), 304 with single primary melanoma (SPM) and 659 convenience controls. Genotype data was generated using the Illumina CoreExome microarray platform, assaying over 500 000 single-nucleotide polymorphisms. A subset of variants were combined to assess a polygenic risk score (PRS) for melanoma.Most MPM cases were diagnosed in patients aged40 years, in sites with visible chronic UV damage. Women and those diagnosed at age ≤ 40 years were less likely to have perilesional UV damage. Patients with MPM had higher frequencies of MITF E318K, MC1R R-alleles and the ASIP risk haplotype. Individuals who had melanoma in a visibly UV-damaged site were more likely to carry MC1R rs75570604 [odds ratio (OR) 2·5], 9q31.2 rs10816595 (OR 1·4) and MTAP rs869329 (OR 1·4). These same alleles were more common in patients with MPM who were diagnosed at age ≤ 40 years. The mean PRS was significantly higher in MPM than in SPM and controls. Naevus count was comparable in early-onset MPM cases and those diagnosed at age40 years.Our cohort demonstrated higher frequencies of previously reported alleles associated with melanoma. MPM melanomas more commonly occur in UV-damaged areas, and these individuals are more likely to carry MC1R red hair colour alleles. Awareness of the interplay of genetic vulnerability with UV damage can stratify risk and guide recommendations for melanoma screening. What's already known about this topic? Skin phenotype, host genotype and ultraviolet (UV) damage all play a role in melanoma development. One of the main risk factors is a personal history of melanoma; second and subsequent primary melanomas account for over 20% of all melanomas registered in Queensland. Multiple loci are associated with melanoma risk, including many low-penetrance loci, which may have a cumulatively significant risk. Population-wide screening programmes for melanoma are not yet economically viable. What does this study add? Patients diagnosed with melanoma at age ≤ 40 years were more likely than older patients to have melanomas in non-UV-damaged sites. Patients with multiple melanomas had higher frequencies of MITF E318K, MC1R R-alleles, and the ASIP extended risk haplotype than patients with single melanoma. CDKN2A, MC1R and MTAP variants were more frequent in patients who developed melanomas at a younger age, but also in those whose melanomas were all on visibly UV-damaged sites. What is the translational message? Incorporating these genetic findings into the known risk factors of skin phenotype and visible UV damage may allow for a more customized and economically feasible approach to early detection of melanoma, particularly in younger patients. Plain language summary available online.

Background: Mobile teledermoscopy is a rapidly advancing technology that promotes early detection and management of skin cancers. Whilst the use of teledermoscopy has proven to be effective and has a role in the detection of skin cancers, patients’ attitudes towards the multiple ways in which this technology can be utilised has not been explored. Methods: Data were obtained from a large randomised controlled trial comparing mobile teledermoscopy-enhanced skin self-examinations (SSEs) with naked-eye SSE. A semi-structured interview guide was developed by the investigators with questions focusing on people’s previous skin screening behaviours and 2 of the major pathways which can be utilised in mobile teledermoscopy: (i) direct-to-consumer and (ii) doctor-to-doctor. All interviews were tape-recorded and transcribed verbatim. Thematic analysis was undertaken by 2 independent researchers. Results: Twenty-eight participants were interviewed. Eighty-six percent of participants (n = 24/28) had previously had a clinical skin examination. Only 18% of participants (n = 5/28) visited the same doctor for each clinical skin examination. Five main themes were identified in the interviews that affected how people felt about the integration of mobile teledermoscopy into skin screening pathways: history of clinical skin examinations, continuity of the doctor-patient relationship, convenience of the direct-to-consumer teledermoscopy, expedited review enhancing the doctor-to-doctor setting and mobile teledermoscopy as a partner-assisted task. Conclusions: Overall mobile teledermoscopy was viewed positively for both direct-to-consumer and doctor-to-doctor interaction. Continuity of care in the doctor-patient relationship was not found to be a priority for clinical skin examination with most participants visiting several doctors throughout their clinical skin examination history.

Background: Screening for skin cancer can be cost‐effective if focused on high‐risk groups. Risk prediction tools have been developed for keratinocyte cancers and melanoma to optimize advice and management. However, few have been validated in a clinical setting over the past few years.Objectives: To assess the clinical utility of risk assessment tools to identify individuals with prevalent skin cancers in a volunteer‐based screening clinic.Methods: Participants were adults presenting for a skin check at a volunteer‐based skin cancer screening facility. We used previously published tools, based on questionnaire responses, to predict melanoma and keratinocyte cancers [KCs; basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] and classified each participant into one of five risk categories. Participants subsequently underwent a full skin examination by a dermatologist. All suspicious lesions were biopsied, and all cancers were histopathologically confirmed.Results: Of 789 people who presented to the clinic, 507 (64%) consented to the study. Twenty‐two BCCs, 19 SCCs and eight melanomas were diagnosed. The proportion of keratinocyte cancers diagnosed increased according to risk category from

Background Amelanotic/hypomelanotic melanoma is associated with poorer outcomes due to a more advanced disease stage at diagnosis. Objective To determine phenotypic risks and genotypic associations with amelanotic/hypomelanotic melanoma to develop a clinical and genetic profile that could assist in identifying high-risk individuals. Methods The Brisbane Naevus Morphology Study conducted from 2009 to 2016 has recruited a core of 1254 participants. Participants were drawn from a combination of volunteers from dermatology outpatient clinics, private dermatology clinics, the Brisbane Longitudinal Twin Study and QSkin study. Case participants had a personal history of melanoma and control participants no personal history of melanoma. We specifically examined seven known candidate pigmentation and melanoma genes and pigmentary phenotypic characteristics in participants with amelanotic/hypomelanotic melanoma compared to pigmented melanomas. This assayed single nucleotide polymorphisms in MC1R, TYR, HERC/OCA2, IRF4, MTAP, PLA2G6 and MITF. Results Forty-seven participants had at least one amelanotic/hypomelanotic melanoma, and 389 had pigmented melanomas, with amelanotic/hypomelanotic melanoma patients significantly older than pigmented melanoma participants (63.3 +/- 13.0 vs. 54.6 +/- 15.3 years; P < 0.001). Amelanotic/hypomelanotic melanoma patients were more likely than pigmented melanoma patients to have red hair (34% vs. 15%; P = 0.01), severe hand freckling (13% vs. 5%; P = 0.01) and propensity to sunburn (63% vs. 44%; P = 0.01). MC1R R/R genotype was much more frequent in our amelanotic/hypomelanotic melanoma population (31.1% vs. 11%; P < 0.001; OR 26.4 vs. 5.9; control 1.0). Amelanotic/hypomelanotic melanoma was associated with TYR rs1126809*A/A [OR (CI 95%) 2.7 (1.1-6.8) vs. 1.2 (0.8-1.9)] and PLA2G6 rs11570734*A/A [OR (CI 95%) 3.7 (1.0-13.6) vs. 1.3 (0.9-2.0)]. The MTAP melanoma risk SNP genotype, associated with darker pigmentation, (rs4636294*A/A) was less common in amelanotic/hypomelanotic melanoma patients [OR (CI 95%) 0.8 (0.3-2.1) vs. 2.0 (1.3-3.1)]. Conclusions Knowledge of phenotypic and genotypic associations of amelanotic/hypomelanotic melanoma can help predict risks and associations of this difficult to diagnose melanoma, which may ultimately assist clinical management and patient skin self-examination.

Melanoma incidence continues to increase across many populations globally and there is significant mortality associated with advanced disease. However, if detected early, patients have a very promising prognosis. The methods that have been utilised for early detection include clinician and patient skin examinations, dermoscopy (static and sequential imaging) and total body photography via 2D imaging. Total body photography has recently witnessed an evolution from 2D imaging with the ability to now create a 3D representation of the patient linked with dermoscopy images of individual lesions. 3D total body photography is a particularly beneficial screening tool for patients at high risk due to their personal or family history or those with multiple dysplastic naevi – the latter can make monitoring especially difficult without the assistance of technology. In this perspective, we discuss clinical examples utilising 3D total body photography, associated advantages and limitations, and future directions of the technology. The optimal system for melanoma screening should improve diagnostic accuracy, be time and cost efficient, and accessible to patients across all demographic and socioeconomic groups. 3D total body photography has the potential to address these criteria and, most importantly, optimise crucial early detection.

Background: Breslow thickness is recognised as one of the most important prognostic tumour features in melanoma. In a recent pooled international study, the interferon regulatory factor-4 (IRF4) intron 4 rs12203592*T single nucleotide polymorphism (SNP) was associated with increased Breslow thickness [1]. Objective: Investigate whether this observation could be extended to include the analysis of IRF4 rs12203592 in nodular melanoma (NM), which is associated with a greater Breslow thickness at diagnosis compared with superficial spreading melanomas. Methods: Participants were recruited as part of the Brisbane Naevus Morphology Study. 432 melanoma case participants, with a personal history of one or more primary melanomas, were analysed along with 662 control individuals with no personal history of melanoma. All participants had genomic DNA extracted from 2ml of saliva collected using an Oragene-DNA selfcollection kit. Results: The IRF4 rs12203592*T allele had a frequency of 36.3% (n= 40) in the NM group compared to cutaneous melanoma group of 24.9% (n= 188), and 22.1% (n=293) in the control group (genotype P =0.015). The odds ratio for carrying the T allele in the NM group was 1.64 (95% confidence interval: 1.09–2.46) compared to the other melanoma patient group. We examined SNPs within an additional seven candidate genes associated with pigmentation, naevogenesis and melanoma (MITF, BNC2, MTAP, TYR, KITLG, HERC2/ OCA2 and PLA2G6) [2] and found no significant association with NM. Conclusions: Our findings report IRF4 as a potentially significant melanoma risk loci in NMs, which is consistent with Gibbs and colleagues findings indicating that the rs12203592* T SNP is associated with increased Breslow thickness in melanoma.