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Introduction: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors., Methods: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases., Results: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%)., Conclusions: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis., Competing Interests: Conflicts of interest This study was partly sponsored by the European Academy of Dermatology and Venerology (EADV), however this did not affect the content of the manuscript. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Genome-wide association studies (GWAS) have identified a number of risk loci for cutaneous melanoma. Cutaneous melanoma shares overlapping genetic risk (genetic correlation) with a number of other traits, including its risk factors such as sunburn propensity. This genetic correlation can be exploited to identify additional cutaneous melanoma risk loci by multitrait analysis of GWAS (MTAG). We used bivariate linkage disequilibrium-score regression score regression to identify traits that are genetically correlated with clinically confirmed cutaneous melanoma and then used publicly available GWAS for these traits in a multitrait analysis of GWAS. Multitrait analysis of GWAS allows GWAS to be combined while accounting for sample overlap and incomplete genetic correlation. We identified a total of 74 genome-wide independent loci, 19 of them were not previously reported in the input cutaneous melanoma GWAS meta-analysis. Of these loci, 55 were replicated (P < 0.05/74, Bonferroni-corrected P-value in two independent cutaneous melanoma replication cohorts from Melanoma Institute Australia and 23andMe, Inc. Among the, to our knowledge, previously unreported cutaneous melanoma loci are ones that have also been associated with autoimmune traits including rs715199 near LPP and rs10858023 near AP4B1. Our analysis indicates genetic correlation between traits can be leveraged to identify new risk genes for cutaneous melanoma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Organ transplant recipients have over 100-fold higher risk of developing skin cancer than the general population and are in need of further preventive strategies. We assessed the possible preventive effects of omega-3 polyunsaturated fatty acid (PUFA) intake from food on the two main skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in kidney and liver transplant recipients., Methods: Adult kidney or liver transplant recipients transplanted for at least 1 year and at high risk of skin cancer were recruited from the main transplant hospital in Queensland, 2012-2014 and followed until mid-2016. We estimated their dietary total long-chain omega-3 PUFAs and α-linolenic acid intakes at baseline using a food frequency questionnaire and ranked PUFA intakes as low, medium, or high. Relative risks (RRs adj ) of skin cancer adjusted for confounding factors with 95% confidence intervals (CIs) were calculated., Results: There were 449 transplant recipients (mean age, 55 years; 286 (64%) male). During follow-up, 149 (33%) patients developed SCC (median 2/person; range 1-40) and 134 (30%), BCC. Transplant recipients with high total long-chain omega-3 PUFA compared with low intakes showed substantially reduced SCC tumour risk (RR adj 0.33, 95% CI 0.18-0.60), and those with high α-linolenic acid intakes experienced significantly fewer BCCs (RR adj 0.40, 95% CI 0.22-0.74). No other significant associations were seen., Conclusion: Among organ transplant recipients, relatively high intakes of long-chain omega-3 PUFAs and of α-linolenic acid may reduce risks of SCC and BCC, respectively.

Patients' phenotypic characteristics might be associated with melanoma aggressiveness, but the evidence is scarce. This study examined the associations be-tween pigmentary characteristics, naevi and melanoma thickness. Data from the Norwegian Women and Cancer (NOWAC) study were analysed. By 2014, 1,243 women were diagnosed with a primary melanoma, and 1,140 had information on thickness. Using ordinal logistic regression models, the probability of being diagnosed with a specific thickness category was calculated by pigmentary score and naevi. Fair pigmentary score was associated with thinner trunk melanomas (probabilities of being diagnosed with a tumour ≤1.0 mm thickness were 74%, 66%, and 51% for fair, medium and dark pigmentary scores, respectively), but not the other sites. High number of naevi was associated with thicker nodular melanoma (NM) but not with super-ficial spreading melanoma. These findings suggest the need for greater overall vigilance and skin checks among women with fair pigmentary score. The association between naevi and NM suggest possible biological mechanisms.

Purpose: To quantify the prevalence of anxiety or depression (overall; melanoma-related) among people with high-risk primary melanoma, their related use of mental health services and medications, and factors associated with persistent new-onset symptoms across 4 years post-diagnosis., Methods: A longitudinal study of 675 patients newly diagnosed with tumor-stage 1b-4b melanoma. Participants completed the Hospital Anxiety and Depression Scale and answered questions about fear of cancer recurrence, use of medication, and support, serially over 4 years. We identified anxiety and depression trajectories with group-based trajectories models and factors associated with persistent symptoms with logistic regression., Results: At diagnosis, 93 participants (14%) had melanoma-related anxiety or depression, and 136 (20%) were affected by anxiety and/or depression unrelated to melanoma. After 6 months, no more than 27 (5%) reported melanoma-related anxiety or depression at any time, while the point prevalence of anxiety and depression unrelated to melanoma was unchanged (16-21%) among the disease-free. Of 272 participants reporting clinical symptoms of any cause, 34% were taking medication and/or seeing a psychologist or psychiatrist. Of the participants, 11% (n = 59) had new-onset symptoms that persisted; these participants were more likely aged < 70., Conclusions: Melanoma-related anxiety or depression quickly resolves in high-risk primary melanoma patients after melanoma excision, while prevalence of anxiety or depression from other sources remains constant among the disease-free. However, one-in-ten develop new anxiety or depression symptoms (one-in-twenty melanoma-related) that persist., Implications for Cancer Survivors: Chronic stress has been linked to melanoma progression. Survivors with anxiety and depression should be treated early to improve patient and, potentially, disease outcomes.

Importance: UV radiation emissions from indoor tanning devices are carcinogenic. Regulatory actions may be associated with reduced exposure of UV radiation at a population level., Objective: To estimate the long-term health and economic consequences of banning indoor tanning devices or prohibiting their use by minors only in North America and Europe compared with ongoing current levels of use., Design, Setting, and Participants: This economic analysis modeled data for individuals 12 to 35 years old in North America and Europe, who commonly engage in indoor tanning. A Markov cohort model was used with outcomes projected during the cohort's remaining life-years. Models were populated by extracting data from high-quality systematic reviews and meta-analyses, epidemiologic reports, and cancer registrations., Main Outcomes and Measures: Main outcomes were numbers of melanomas and deaths from melanoma, numbers of keratinocyte carcinomas, life-years, and health care and productivity costs. Extensive sensitivity analyses were performed to assess the stability of results., Results: In an estimated population of 110 932 523 in the United States and Canada and 141 970 492 in Europe, for the next generation of youths and young adults during their remaining lifespans, regulatory actions that ban indoor tanning devices could be expected to gain 423 000 life-years, avert 240 000 melanomas (-8.2%), and avert 7.3 million keratinocyte carcinomas (-7.8%) in North America and gain 460 000 life-years, avert 204 000 melanomas (-4.9%), and avert 2.4 million keratinocyte carcinomas (-4.4%) in Europe compared with ongoing current levels of use. Economic cost savings of US $31.1 billion in North America and €21.1 billion (US $15.9 billion) in Europe could occur. Skin cancers averted and cost savings after prohibiting indoor tanning by minors may be associated with one-third of the corresponding benefits of a total ban., Conclusions and Relevance: Banning indoor tanning may be associated with reduced skin cancer burden and health care costs. Corresponding gains from prohibiting indoor tanning by minors only may be smaller.

Background: Lung transplant recipients (LTRs) are at very high risk of skin cancer. Omega-3 fatty acids (FAs) are anti-inflammatory and immune-modulating and could potentially reduce this risk. We assessed the feasibility of omega-3 FA supplementation to reduce skin cancer among these patients., Methods: LTRs aged 18 + years, at least 1 year post-transplant, were recruited from the outpatient clinic of The Prince Charles Hospital, Brisbane. Participants were randomly allocated to 4-times-daily supplements containing either omega-3 FA (3.36 eicosapentaenoic acid [EPA] + docosahexaenoic acid) or placebo (4 g olive oil) for 12 months. Primary outcomes were rates of recruitment, retention, adherence (assessed by plasma omega-3 FA), and safety. Secondary outcomes were incident skin cancers., Results: Among 106 eligible lung transplant recipients, 49 consented to take part (46%) with 25 allocated to omega-3 FA and 24 to placebo supplements. Of these, 22 (88%) and 20 (83%), respectively, completed the trial. After 12 months, median plasma EPA increased substantially in the intervention group (125.0 to 340.0 µmol/L), but not the placebo group (98.0 to 134.5 µmol/L). In the intervention group, 6 patients developed skin cancers compared with 11 in the placebo group, giving an odds ratio (95% confidence interval) of 0.34 (0.09 to 1.32). There were no serious, active intervention-related adverse events., Conclusions: This pilot trial among LTRs showed acceptable recruitment and high retention and adherence. We demonstrated a signal for reduction of new skin cancer cases in those taking omega-3 FA supplements, which supports the notion that a larger, more definitive trial is warranted., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A proportion of cutaneous melanomas display neval remnants on histologic examination. Converging lines of epidemiologic and molecular evidence suggest that melanomas arising from nevus precursors differ from melanomas arising de novo. In a large, population-based study comprising 636 cutaneous melanomas subjected to dermatopathology review, we explored the molecular, host, and environmental factors associated with the presence of neval remnants. We found that nevus-associated melanomas were significantly associated with younger age at presentation, non-brown eye color, trunk site, thickness of less than 0.5 mm, and BRAF V600E mutation. Compared with patients with de novo melanomas, those with nevus-associated tumors were more likely to self-report many moles on their skin as a teenager (odds ratio = 1.94, 95% confidence interval = 1.01-3.72) but less likely to report many facial freckles (odds ratio = 0.49, 95% confidence interval = 0.25-0.96). They also had high total nevus counts (odds ratio = 2.18, 95% confidence interval = 1.26-3.78). On histologic examination, nevus-associated melanomas exhibited less dermal elastosis in adjacent skin compared with de novo melanomas (odds ratio = 0.55, 95% confidence interval = 0.30-1.01). These epidemiologic data accord with the emerging molecular paradigm that nevus-associated melanomas arise through a distinct sequence of causal events that differ from those leading to other cutaneous melanomas., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Published findings on the associations between smoking and the incidence of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are inconsistent. We aimed to generate prospective evidence on these relationships overall and by anatomical site., Methods: We followed 1,223,626 women without prior cancer by electronic linkage to national cancer registration data. Questionnaire information about smoking and other factors was recorded at recruitment (1996-2001) and every 3-5 years subsequently. Cox regression yielded adjusted relative risks (RRs) comparing smokers versus never-smokers., Results: After 14 (SD4) years follow-up per woman, 6699 had a first registered cutaneous SCC and 48,666 a first BCC. In current versus never-smokers, SCC incidence was increased (RR = 1.22, 95% CI 1.15-1.31) but BCC incidence was decreased (RR = 0.80, 0.78-0.82). RRs varied substantially by anatomical site; for the limbs, current smoking was associated with an increased incidence of SCC (1.55, 1.41-1.71) and a decreased incidence of BCC (0.72, 0.66-0.79), but for facial lesions there was little association of current smoking with either SCC (0.93, 0.82-1.06) or BCC (0.92, 0.88-0.96). Findings in meta-analyses of results from this and seven other prospective studies were largely dominated by the findings in this study., Conclusions: Smoking-associated risks for cutaneous SCC and BCC are in the opposite direction to each other and appear to vary by anatomical site.

Objective: Because melanoma patients are at high risk of further disease, we aimed to study their melanoma prevention behaviours., Methods: In a large cohort of patients newly diagnosed with high-risk melanoma in Queensland, Australia, we assessed clustering of preventive behaviours using latent class analysis. We assessed associated factors with prevalence proportion ratios (PPRs) and 95% confidence intervals (CIs) estimated by Poisson regression and also if preventive behaviour was associated with better tumour prognosis at diagnosis., Results: Among 789 primary melanoma patients (57% male; 21% with previous melanoma), we identified 4 different behaviour clusters: "no/ low prevention" (34% of cohort), "sun protection only" (25%), "skin checks only" (25%), and "sun protection and skin checks" (17%). Prevalence of clusters differed between males and females and also the component behaviours. Preventive behaviours were associated with having skin that burned and past cutaneous cancer, and for males, combined sun protective and skin checking behaviour was associated with higher education and non-smoking. In patients with no past history of cutaneous cancer, males in the "skin checks only" cluster had significantly reduced chances of a thick (poor prognosis) melanoma (PPR = 0.79, 95% CI 0.68, 0.91) and females in the "sun protection and skin checks" cluster were significantly less likely to have an ulcerated melanoma (PPR = 0.85, 95% CI 0.74, 0.98) compared with the "no/ low prevention" cluster., Conclusion: These findings allow tailoring of preventive advice to melanoma patients to reduce their risk of future primary and recurrent disease., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Several new members of the human polyomavirus (HPyV) family that infect human skin and are potentially oncogenic have been identified in the last decade., Objectives: To investigate prospectively the seroprevalence and stability of 13 PyVs, and possible associations with different risk factors and cutaneous squamous cell carcinoma (cSCC)., Study Design: In this Australian population-based longitudinal study sera were collected at baseline in 1992 or during the next 4 years from 688 people. Of the 688, 226 developed a new cSCC between blood collection and the final follow up in 2003. The remaining 462 served as controls. Among the 462 controls, 161 had a second serum sample from 2003 analysed. Seroprevalence of 10 human PyVs (BKV, JCV, KIV, WUV, MCV, TSV, HPyV6, HPyV7, HPyV9 and HPyV10) and three non-human PyVs (SV40, LPV and ChPyV) was assessed using multiplex serology., Results: There was no significant difference in PyV seroprevalence between people who developed cSCC during follow-up compared to those who did not. WUV and HPyV10 showed the highest serostability (93%) and JCV VP1 and SV40 VP1 the lowest (84%) over a 9-year time period (range 7-11 years)., Conclusions: We found no evidence that HPyV seroprevalence is associated with subsequent development of cSCC and observed variable stability of antibodies to polyomaviruses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sunlight is the principal environmental risk factor for keratinocyte cancers, but other carcinogens have also been implicated, including tobacco smoke. Findings have been conflicting, however. We investigated associations between cigarette smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained through data linkage and verified by histopathology reports. We restricted analyses to white participants who at baseline reported no past history of skin cancer excisions and no more than five destructively treated actinic skin lesions. We fitted Cox proportional hazards models, adjusted for known confounders. Compared with never smokers, current smokers had significantly lower risks of BCC (hazard ratio = 0.6; 95% confidence interval = 0.4-0.9) but significantly higher risks of SCC (hazard ratio = 2.3; 95% confidence interval = 1.5-3.6). Former smokers had similar risks for BCC and SCC as never smokers. Among smokers, we observed no dose-response trends with duration of smoking, intensity, or time since quitting. On further analysis, current smokers had fewer skin examinations and procedures than never smokers, suggesting greater opportunities for detection among never smokers. Strengths include large sample size, prospective design, and virtually complete follow-up; however, histologic details were missing for a proportion of excised tumors. In conclusion, current smokers had a lower incidence of BCC (possibly because of detection bias) but higher rates of SCC., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to describe variations in unmet supportive care needs of patients diagnosed with localised melanoma at high risk of recurrence and factors associated with initial and persisting moderate-to-high needs., Methods: We ascertained 386 patients diagnosed with clinical stage IB-II melanoma and administered surveys every 6 months for 2 years. The proportion experiencing at least one moderate-to-high need was assessed among salient subgroups: 306 patients with no previous melanoma and 80 with previous melanoma at enrolment, 30 who experienced disease recurrence during follow-up and 31 who developed another primary. Baseline factors associated with (a) needs at enrolment and (b) persistent needs over 2 years (or as long as disease-free) were identified by logistic regression analyses., Results: The proportion of patients with needs substantially declined over the first 6 months (if no previous melanoma, from 48 to 22 %, p < 0.001; previous melanoma, 35 to 17 %, p = 0.007), and in those remaining disease-free, needs declined further by 24 months (to 14 and 6 % respectively). By contrast, 50 % of those experiencing recurrence, and 39 % of those who developed another primary, reported needs. Stressful life events and anxiety were associated with needs at enrolment. At least one need, mainly fear of recurrence, persisted in 22 % of disease-free participants. Persistent needs were predicted by age, depression, anxiety and other stressful life events., Conclusions: Melanoma patients' needs peak when first diagnosed and if disease recurs. Younger people or those experiencing additional stressful events, anxiety or depression are more likely to experience persistent needs and may benefit from tailored support.

Clinicians are concerned that treatment of rheumatoid arthritis (RA) with tumour necrosis factor alpha antagonists (TNFα biologics) may increase patients' risk of melanoma compared with treatment with nonbiologic disease-modifying antirheumatic drugs (nbDMARDS). We aimed to assess the risk of melanoma in RA patients treated with TNFα biologics compared with RA patients treated with nbDMARDS. A secondary aim was to quantify the risk of melanoma in RA patients treated with TNFα biologics compared with the general population. We carried out a systematic review and meta-analysis searching Medline, Embase and the ISI Science Citation Index databases to January 2016. Cohort studies that enabled a quantitative assessment of the risk of melanoma in RA patients treated with TNFα biologics compared with either RA patients treated with nbDMARDS or the general population or both were included. Data were pooled using a random-effects model. From 812 articles, we identified six that fulfilled the inclusion criteria. Four studies reported on the risk of melanoma in RA patients treated with TNFα biologics compared with those treated with nbDMARDS, with a pooled effect estimate of 1.60 (95% confidence interval 1.16-2.19). Five reported on the risk of melanoma in RA patients treated with TNFα biologics compared with the general population, and the pooled effect estimate was 1.87 (95% confidence interval 1.53-2.30). There was no significant heterogeneity in either analysis. This systematic review and meta-analysis does not allay clinician's fears and, while awaiting further evidence from large collaborative studies, this patient population may benefit from regular skin checks and counselling to avoid excessive sun exposure.

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The potential influence of measured body weight and height on keratinocyte skin cancer risk has scarcely been studied. Some evidence indicates melanoma risk increases as self-reported height increases, but an association with body mass index (BMI) is less certain., Methods: We measured body weight and height of 1171 Australian men and women in a community-based skin cancer study in Queensland and prospectively examined the association of BMI, body surface area (BSA) and height and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma while accounting for skin phenotype, sun exposure, clinical/cutaneous signs of chronic photodamage and other risk factors., Results: During 16 years of follow-up, 334 and 188 participants newly developed BCC and SCC, respectively; 28 participants were diagnosed with primary melanoma. BMI and BSA were unrelated to skin cancer incidence. After full adjustment, height was significantly associated with SCC development in men (relative risk (RR)=1.66; 95% confidence interval (CI)=1.11-2.48, for ≥175cm vs ≤171cm, Ptrend=0.017), and BCC in women (Ptrend=0.043). Melanoma in men, was similarly positively associated with height (RR per 5cm increment=1.55; 95%CI 0.97-2.47, P=0.067) though not significantly., Conclusion: This study shows that after adjusting for sun exposure tall stature may be a risk factor for the most common types of skin cancer BCC, SCC, and melanoma, while body mass and surface area appear unrelated to risk., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Using a large (N= 25 493) population-based cohort from Queensland, Australia, we compared melanoma survival among cases with a single invasive melanoma only against those who also had a diagnosis of a single in situ melanoma. After adjustment for sex, age, body site, clinicopathological subtype, thickness and ulceration, it was found that there was no difference (P = 0.99) in 10-year melanoma-specific mortality following a diagnosis of an invasive lesion, whether or not an in situ melanoma was also present. We conclude that in situ melanomas do not alter the prognosis of an invasive melanoma., (© 2016 The Australasian College of Dermatologists.)

Background: Evidence for an association between aspirin or other nonsteroidal antiinflammatory drug (NSAID) use and basal cell carcinoma (BCC) has been inconsistent., Objective: We conducted a systematic review and metaanalysis to assess the effect of oral NSAIDs on BCC., Methods: PubMed, Web of Science, and Embase databases were searched up to December 3, 2014. A random effects model metaanalysis was used to calculate summary estimates of the effects of aspirin, nonaspirin NSAIDs, or any (aspirin or nonaspirin) NSAID use in patients with BCC., Results: The summary estimates from 11 studies (1 randomized controlled trial, 5 cohort studies, and 5 case control studies) found a 10% risk reduction of BCC among those using any NSAID (relative risk [RR], 0.90 [95% confidence interval {CI}, 0.84-0.97]). A similar but not statistically significant inverse association was observed for nonaspirin NSAIDs (RR, 0.93 [95% CI, 0.86-1.02]), while aspirin use was more weakly associated (RR, 0.95 [95% CI, 0.91-1.00]). The strongest inverse associations were noted among those with either a history of skin cancers or a high prevalence of actinic keratoses., Limitations: Dose-effect estimates could not be calculated because the available data were too heterogeneous to pool., Conclusion: The intake of NSAIDs may help prevent BCC, particularly in high-risk populations. A large randomized controlled trial is required to confirm these findings., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Transplant recipients have a raised risk of melanoma but the relative magnitude is uncertain. We undertook a systematic review by searching major databases for relevant publications to June 2014. Cohort studies quantifying the association between transplantation and melanoma were included and data were pooled using the weighted average method. Among 20 eligible studies the pooled relative risk (pRR) of melanoma was 2.71 (95% confidence interval (CI), 2.23-3.30) with significant heterogeneity (p < 0.001). There was no indication of publication bias. Sub-group analyses by study design, follow-up period, adjustment for confounding and quality score did not materially alter results. Among liver and heart transplant patients pRR for melanoma was 5.27 (95% CI 4.50-6.62), higher than the pRR of 2.54 (95% CI 2.18-2.96) among kidney transplant patients. Transplant recipients are at more than double the risk of melanoma overall compared with the general population.

White populations in Australia and England share many genetic and phenotypic characteristics due to common ancestry, but Australians experience far higher rates of melanoma due to higher ambient ultraviolet radiation (UVR) levels. To gain insight into the role of UVR on melanoma development early in life, we used national cancer registration data and compared recent incidence rates and long-term trends of primary invasive cutaneous melanoma in Australian and English youth aged 0-24 years diagnosed 1990-2010. Incidence rates and standardized rate ratios (SRRs) with 95% confidence intervals (CIs) for 2006-2010 were calculated and incidence trends across the whole period were examined using JoinPoint regression. In Australian youth, overall melanoma incidence was double that in English youth (2.2 and 1.1 per 100,000, respectively). While melanoma rates were similarly rare among children <10 years in both countries, in subsequent 5-year age groups, incidence was significantly higher in Australia compared to England. Melanoma incidence among 15-24 year olds significantly increased by more than 2% per year in both sexes in England. However, after an initial non-significant increase, Australian rates for this older age group significantly decreased by 6.0% (95% CI, -8.2 to -3.8) per year in females from 1997 and decreased by 12.4% (95% CI, -20.3 to -3.8) per year in males from 2004. Long-standing primary prevention strategies targeted at curbing UVR exposure appear to have been effective in mitigating incidence trends in Australian youth, but decreases in incidence in English youth are yet to be observed., (© 2015 UICC.)

Background: Knowledge of variation in diagnosis and surgery in high-risk primary melanoma patients is limited. We assessed frequency and determinants of diagnostic procedures, wide local excision (WLE) and sentinel lymph node biopsy (SLNB)., Methods: People in Queensland newly diagnosed with melanoma, clinical stage 1b or 2, were recruited prospectively. Patient information was collected from questionnaires and pathology records. Differences in surgical procedures in relation to host and tumor characteristics were assessed., Results: In 787 participants, primary melanoma was diagnosed by surgical excision (74%), shave (14%), punch (12%) or incisional (1%) biopsy. General practitioners (GPs) diagnosed 80%. Diagnostic procedure differed by remoteness of residence, health sector, treating doctor's specialty and melanoma site and thickness. 766 patients had WLE, 86% by surgeons. Of 134 residual melanomas, 13 (10%) were ≤ 1 mm at diagnosis but > 1 mm at WLE, mostly after shave biopsy. SLNB was performed in 261 (33%) patients. SLNB was more common in those under 50, in remoter locations or treated by GP initially, and less common with head and neck melanoma., Conclusion: Diagnostic and surgical procedures for primary melanoma vary substantially and partial biopsy can influence initial tumor microstaging. Patient, tumor and doctor characteristics influence SLNB practice., (© 2015 Wiley Periodicals, Inc.)

While actinic keratoses (AKs) have a known association with cutaneous squamous cell carcinoma (SCC), the relation of actinic field change to SCC has not been quantified. This study investigated the presence of field change and AKs in renal transplant recipients (RTRs) and estimated SCC risk. In May 2010 to October 2011, a dermatologist examined 452 white RTRs (mean age 53 years) at two hospitals in Manchester, UK, counting AKs and recording field change presence by body site and SCCs arising during the study period. Of the participants 130 (29%) had AKs at examination. In 60 (13%) RTR patients with AKs but no field change, 4 (7%) developed SCCs, compared with 15 (21%) of the 70 (15%) with AKs and field change. SCCs developed directly within field change areas in 11/15 (73%) RTRs. This study confirms that RTRs with widespread confluent actinic skin damage are at very high risk of SCC and should be monitored closely.

Importance: Primary prevention and early detection are integral strategies to reduce the burden of skin cancer., Objectives: To describe the prevalence of sun protection and skin examination practices in a population exposed to high levels of ambient solar radiation and to identify associated factors., Design, Setting, and Participants: Cross-sectional analyses of baseline data from a prospective cohort of 40,172 adults aged 40 through 69 years from Queensland, Australia, recruited in 2011. We obtained data on all melanoma diagnoses through 2009 via record linkage with the Queensland Cancer Registry (notifications have been mandatory since 1982)., Main Outcomes and Measures: We calculated prevalence proportion ratios to compare prevalence of sun protection and skin examination practices in 3 separate groups: those with a history of melanoma (group 1), those with a self-reported history of treated actinic lesions (group 2), and those without either (group 3). We used multivariate generalized linear models to identify factors associated with each practice., Results: Participants with a previously confirmed melanoma (group 1; n = 1433) and/or treated actinic lesions (group 2; n = 24,006) were more likely than those without (group 3; n = 14,733) to report sun protection practices, including regular use of sunscreen (53.3%, 45.1%, and 38.1%, respectively) and wearing hats (74.7%, 68.2%, and 58.2%, respectively). They were also more likely to have had a whole-body skin examination by a physician in the past 3 years (93.7%, 83.4%, and 52.1%, respectively). Within all 3 groups, the strongest association with sun protection practices was with sun-sensitive skin type. Within group 3 (no history of treated skin lesions), the strongest factor associated with clinical skin examinations was self-reported nevus density at 21 years of age, whereas a family history of melanoma was a significant factor in groups 2 and 3., Conclusions and Relevance: In this large sample exposed to high levels of ambient solar radiation, sun protection and skin examination practices were most frequent among those with a history of treated skin lesions or sun-sensitive skin types.

Objective: The aim of this paper is to determine levels of supportive care needs, anxiety, depression and symptoms amongst patients newly diagnosed with localised invasive primary melanoma and if these varied amongst patients who had a sentinel lymph node biopsy (SLNB). We also considered quality of life compared with general population norms., Methods: Patients newly diagnosed with clinical stage IB-II invasive melanoma were ascertained through Queensland hospitals, specialist clinics and pathology laboratories. Validated surveys measured 46 need items (Supportive Care Needs Survey-Short Form + melanoma subscale), anxiety and depression (Hospital Anxiety and Depression Scale) and quality of life and symptoms (Functional Assessment of Cancer Therapy-Melanoma). Regression models compared outcomes according to whether or not participants had a SLNB., Results: We surveyed 386 patients, 155 before and 231 after wide local excision, of whom 46% reported ≥1 moderate-level or high-level unmet need. The three highest needs were for help with fears about cancer spreading (17%), information about risk of recurrence (17%) and outcomes when spread occurred (16%). Those who had a SLNB were more likely to report a moderate or high unmet need for help with uncertainty about the future or with lymphoedema (p < 0.05). Overall, 32% of participants had anxiety and 15% had depression regardless of performance of SLNB. Melanoma-specific symptoms were worse in SLNB patients (p = 0.03). Compared with the general population, emotional well-being was lower amongst melanoma patients., Conclusions: A substantial proportion of newly diagnosed patients with localised invasive melanoma need further melanoma-specific information and support with psychological concerns. Patients who have a SLNB clear of disease may need help with symptoms after surgery., (Copyright © 2014 John Wiley & Sons, Ltd.)

Cutaneous melanomas are postulated to arise through at least two causal pathways, namely the "chronic sun exposure" and "nevus" pathways. While chronic sun exposure probably causes many head/neck melanomas, its role at other sites is unclear. In a population-based, case-case comparison study conducted in Brisbane, Australia, we determined the prevalence and epidemiologic correlates of chronic solar damage in skin adjacent to invasive, incident melanomas on the trunk (n = 418) or head/neck (n = 92) among patients aged 18-79 in 2007-2010. Participants self-reported information about environmental and phenotypic factors, and a dermatologist counted nevi and actinic keratoses. Dermatopathologists assessed solar elastosis adjacent to each melanoma using a four-point scale (nil, mild, moderate, marked), and noted the presence or absence of adjacent neval remnants. We measured associations between various factors and solar elastosis using polytomous logistic regression. Marked or moderate solar elastosis was observed in 10% and 27%, respectively, of trunk melanomas, and 60% and 17%, respectively, of head/neck melanomas. At both sites, marked elastosis was positively associated with age (p(trend)  < 0.0001) and inversely associated with neval remnants (p(trend)  < 0.001). For trunk melanomas, marked elastosis was associated with highest quartiles of total sun exposure [odds-ratio (OR) = 5.47, 95% confidence interval (CI) = 1.08-27.60] and facial freckling (OR = 2.98, 95% CI = 1.17-7.56), and inversely associated with deeply tanning skin (OR = 0.29, 95% CI = 0.08-1.11) and high nevus counts (OR = 0.08, 95% CI = 0.01-0.66). Mostly similar associations were observed with moderate solar elastosis. About one in three trunk melanomas in Queensland have evidence of moderate-to-marked sun damage, and they differ in risk associations from those without., (© 2014 UICC.)

Identifying people at high risk of melanoma is important for targeted prevention activities and surveillance. Several tools have been developed to classify melanoma risk, but few have been independently validated. We assessed the discriminatory performance of six melanoma prediction tools by applying them to individuals from two independent data sets, one comprising 762 melanoma cases and the second a population-based sample of 42,116 people without melanoma. We compared the model predictions with actual melanoma status to measure sensitivity and specificity. The performance of the models was variable with sensitivity ranging from 97.7 to 10.5% and specificity from 99.6 to 1.3%. The ability of all the models to discriminate between cases and controls, however, was generally high. The model developed by MacKie et al. (1989) had higher sensitivity and specificity for men (0.89 and 0.88) than women (0.79 and 0.72). The tool developed by Cho et al. (2005) was highly specific (men, 0.92; women, 0.99) but considerably less sensitive (men, 0.64; women, 0.37). Other models were either highly specific but lacked sensitivity or had low to very low specificity and higher sensitivity. Poor performance was partly attributable to the use of non-standardized assessment items and various differing interpretations of what constitutes "high risk".

Nonsteroidal anti-inflammatory drugs (NSAIDS) have received increasing attention as potential chemopreventive agents of skin cancer, but evidence is inconsistent. To investigate whether the use of aspirin and other NSAIDS reduces the risk of squamous cell carcinoma (SCC), we conducted a systematic review on the basis of published epidemiologic studies and calculated summary estimates for aspirin, nonaspirin NSAIDS, and any NSAIDS use. Summary estimates from nine studies (five case-control, three cohort, and one intervention) indicated significantly reduced risks of SCC among users of nonaspirin NSAIDS (relative risk (RR) 0.85, 95% confidence interval (CI) 0.78-0.94) and among users of any NSAIDS (RR 0.82, 95% CI 0.71-0.94) compared with nonusers with the effect seen particularly in those with previous actinic skin tumors. A reduced risk was also observed among aspirin users, although with borderline statistical significance (RR 0.88 95% CI 0.75-1.03). There was significant heterogeneity between studies regarding SCC risk estimates for aspirin use and any NSAIDS use. These findings suggest that NSAIDS collectively have the potential to prevent the development of cutaneous SCC.

Whether susceptible people develop both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) or one type exclusively during life is unknown. We investigated this in an Australian community cohort of 1,191 adults aged 25-75 years by recording all new BCCs and SCCs for 16 years in people with no previous keratinocyte cancer. Among those who developed multiple skin cancers, age- and sex-specific incidence rates per 100,000 were calculated for those who developed BCC exclusively, SCC exclusively, or BCC and SCC. Corresponding relative risks (and 95% confidence intervals) were estimated by Poisson regression. During follow-up, 116 people developed multiple keratinocyte cancers: 65 (56%) developed BCC exclusively (range 2-8 per person); 18 (16%) developed SCC exclusively (2-5 per person); and 28% developed both types. Of the 116, 88 had a BCC first, of whom 74% subsequently developed only BCCs, and 28 had SCC first, of whom 64% subsequently developed only SCCs. Incidence rates did not differ by sex in the BCC-only, SCC-only, or mixed groups, but they increased significantly with age especially in the SCC-only group. These findings suggest that the majority of people are prone to develop one type rather than a mix of keratinocyte cancers.

Cutaneous melanoma is a relatively common cancer in adolescents and young adults in Australia, but detailed information about occurrence patterns and prognosis is limited. We evaluated incidence trends from 1982 to 2010 and recent survival rates in those aged 15-24 years in the state of Queensland. In situ and invasive melanoma cases were identified from the Queensland Cancer Registry. Incidence rates were age-standardised to the 2000 World population and trends calculated using joinpoint regression. Five-year relative survival was estimated by the period method and Poisson models were used to produce adjusted mortality hazard ratios. Average annual incidence rates for the 5-year period 2006-2010 were 6.3 per 100,000 [95% confidence interval (CI) 5.4, 7.2] for in situ and 10.1 per 100,000 (95% CI 9.0, 11.3) for invasive melanoma. Since the mid-1990s, incidence rates for in situ melanomas have been stabilizing while invasive melanoma has decreased in both sexes, mainly owing to declining rates of thin tumours (≤1 mm) (-5.4% per year, 95% CI -8.3%, -2.4%). Incidence rates of melanomas >1 mm in thickness have remained relatively unchanged since 1991 however. In the period 2006-2010, relative 5-year survival of 15-24 year olds with invasive melanoma was 95.7% (95% CI 92.9%, 97.5%). The subgroup with tumours >1 mm was nearly six times more likely to die within 5 years than those with thin tumours (adjusted hazard ratio = 5.53, 95% CI 1.72, 17.80). Incidence of thin melanoma in young people in Queensland is declining, suggesting benefits of primary prevention efforts are being realised., (© 2014 The Authors Published by Wiley Periodicals, Inc. on behalf of UIC.)

Tea consumption has been shown to protect against skin carcinogenesis in laboratory-based studies; however, epidemiological evidence is limited and inconsistent. This prospective study examined the association between black tea consumption and the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Usual black tea consumption was estimated from food frequency questionnaires completed in 1992, 1994, and 1996 by 1,325 Australian adults. All histologically confirmed skin cancers diagnosed in participants from 1997 to 2007 were recorded. Relative risks (RRs) and 95% confidence intervals (CIs) were assessed using generalized linear models with Poisson and negative binomial distributions and adjusted for confounding factors including skin phenotype and sun exposure. Compared with never drinking black tea, drinking ≥4 cups/day was not associated with BCC (RR = 1.03, 95% CI: 0.70-1.53; P-trend = 0.74) or SCC (RR = 1.25, 95% CI: 0.71-2.19; P-trend = 0.29) in person-based analyses. Stratification by previous history of skin cancer as well as tumor-based analyses also showed no significant associations between black tea intake and incidence of BCC or SCC tumors. Our results do not support the hypothesis that high black tea consumption reduces risk of skin cancer, including in people with a previous history of skin cancer.

Background: Organ transplant recipients (OTRs) have a high risk of skin cancer, and excessive sun exposure is a major contributing factor., Objective: To document the prevalence of sun protection and associated factors in OTRs in Queensland, Australia., Methods: Cross-sectional study of the frequency of wearing hats, long sleeves and using sunscreens among OTRs and factors associated with regular use. Adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression models., Results: Among 446 OTRs, 66, 49 and 39% wore a hat, sunscreen and long sleeves, respectively, mostly when outdoors. 52% regularly practiced multiple sun protection measures while 19% did not. Sunburn-prone skin (PR = 1.43, 95% CI = 1.06-1.93) and frequent whole-body skin examinations (PR = 1.48, 95% CI = 1.19-1.84) were independently associated with regular use of multiple sun protection measures., Conclusion: Findings are consistent with sun-conscious OTRs also having more regular skin screening and that having frequent skin examinations promotes sun-protective habits., (© 2015 S. Karger AG, Basel.)

Introduction: Cutaneous squamous cell carcinoma is a malignant tumour of keratinocytes arising in the epidermis, with histological evidence of dermal invasion. Incidence varies by country, skin colour, and outdoor behaviour, and is as high as 400/100,000 in Australia. People with fair skin colour who have high sun exposure and sunburn easily with little or no tanning, people with xeroderma pigmentosum, and people who are immunosuppressed are most susceptible to squamous cell carcinoma., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: Does the use of sunscreen help prevent cutaneous squamous cell carcinoma and actinic (solar) keratosis? What is the optimal margin for primary excision of cutaneous squamous cell carcinoma (non-metastatic)? Does radiotherapy after surgery affect local recurrence of cutaneous squamous cell carcinoma in people with squamous cell carcinoma of the skin (non-metastatic)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2013 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found five studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: sunscreens, primary excision, and radiotherapy after surgery.

Objective: Following the introduction of highly active antiretroviral therapy (HAART) the risk of AIDS-defining cancers decreased but incidence of many non-AIDS-defining cancers has reportedly increased in those with HIV/AIDS. Whether melanoma risk has also changed in HIV/AIDS patients post-HAART is unknown and therefore we evaluated this in comparison with the risk before HAART., Design: Systematic review and meta-analysis., Methods: We searched Medline, Embase and ISI science citation index databases to April 2013. All cohort studies of patients diagnosed with HIV/AIDS that permitted quantitative assessment of the association with melanoma were eligible. Detailed quality assessment of eligible studies was conducted, focussing particularly on adjustment for ethnicity, a priori considered essential for an unbiased assessment of melanoma risk. Data were pooled using a random effects model., Results: From 288 articles, we identified 21 that met the inclusion criteria, 13 presenting data for the post-HAART era and 8 for the pre-HAART era. Post-HAART the pooled relative risk (pRR) for the association between HIV/AIDS and melanoma was 1.26 (95% CI, 0.97-1.64) and 1.50 (95% CI 1.12-2.01) among studies that accounted for ethnicity, with evidence of significant heterogeneity (P = 0.004, I2 = 55.5). Pre-HAART pRRs were 1.26 (95% CI 1.11-1.43; P het = 0.82) and 1.28 (95% CI 1.10-1.49) among studies adjusted for ethnicity., Conclusions: People with HIV/AIDS remain at a significantly increased risk of developing melanoma in the post-HAART era. White skinned people with HIV/AIDS should be screened regularly and counselled against excessive sun exposure.

Application of sunscreen to the skin is widely used as an adjunct strategy, along with wearing protective clothing and seeking shade, to protect against skin cancer and photoaging that result from excessive sun exposure. Many epidemiological studies of case-control and cohort study design have studied the effects of sunscreen use on skin cancer, and more recently photoaging, but their findings have been mostly uninformative. This review of results of randomized controlled trials shows that the evidence, though limited, supports beneficial effects of sunscreen application on the occurrence of skin cancers and skin photoaging., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Caffeine may repair skin damage induced by excessive exposure to ultraviolet light. The purpose of this study was to investigate the association between caffeine intake and incidence of basal cell (BCC) and squamous cell carcinoma (SCC). We also assessed the associations between coffee consumption and incidence of these skin cancers., Methods: Caffeine intake and consumption of coffee were estimated from food frequency questionnaires assessed in 1992, 1994, and 1996 among 1,325 randomly selected adult residents of a subtropical Australian community. All histologically confirmed tumours of BCC and SCC occurring between 1997 and 2007 were recorded. Associations with BCC and SCC were assessed using Poisson and negative binomial regression models and were adjusted for confounders including skin type and indicators of past sun exposure., Results: There was no association between total caffeine intake and incidence of BCC or SCC. Participants with prior skin cancers, however, had a 25% lower risk of BCC if they were in the highest tertile of total caffeine intake (equivalent to daily consumption of four cups of regular coffee) compared with the lowest tertile (multivariable RR 0.75; 95% CI 0.57-0.97, P trend = 0.025). There was no dose-response relationship with SCC. Consumption of neither caffeinated nor decaffeinated coffee was associated with BCC or SCC., Conclusions: Among people with prior skin cancers, a relatively high caffeine intake may help prevent subsequent BCC development. However, caffeine intake appears not to influence the risk of SCC.

Background: Cutaneous melanomas have been hypothesized to arise through different pathways according to phenotype, body site, and sun exposure. To further test this hypothesis, we explored associations between phenotype and melanoma at different sites using a case-case comparative approach., Methods: Melanoma patients (n = 762) aged 18 to 79 years and diagnosed from 2007 to 2010 were ascertained from pathology laboratories in Brisbane, Australia. Patients reported phenotypic information and a dermatologist counted melanocytic nevi and solar keratoses. We compared data for patients with trunk melanoma (n = 541, the reference group), head/neck melanoma (n = 122), or lentigo maligna melanoma (LMM) of the head/neck (n = 69). ORs and 95% confidence intervals were calculated using classical or polytomous logistic regression models., Results: Compared with trunk melanoma patients, those with head/neck melanoma were significantly less likely to have high nevus counts (≥135: OR = 0.27; Ptrend = 0.0004). Associations between category of nevus count and LMM head/neck were weaker and significantly different (≥135: OR = 1.09; Ptrend = 0.69; Phomogeneity = 0.02). Patients with head/neck melanoma were more likely than those with truncal melanoma to have high solar keratosis counts (≥7: OR = 1.78, Ptrend = 0.04). Again, associations with LMM head/neck were weaker, albeit not significantly different (≥7: OR = 1.61; Ptrend = 0.42; Phomogeneity = 0.86)., Conclusion: Trunk melanomas are more strongly associated with nevus counts than head/neck melanomas, but are less strongly associated with number of solar keratoses, a marker of chronic sun exposure., Impact: These findings underscore the notion that melanomas on the trunk typically arise through a causal pathway associated with nevus propensity, whereas melanomas on the head/neck arise through a pathway associated with cumulative sun exposure., (©2013 AACR.)

Laboratory-based evidence suggests that omega-3 and omega-6 polyunsaturated fatty acids may affect skin photocarcinogenesis, but epidemiologic evidence is inconsistent. In 1,191 White Australian adults, we prospectively investigated associations between baseline plasma concentrations of omega-3 and omega-6 fatty acids and cutaneous basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). Relative risks (RR) and 95% confidence intervals (CI) were estimated on the basis of number of histologically confirmed tumors diagnosed during follow-up (1997-2007). Plasma eicosapentaenoic acid (EPA) concentrations and omega-3/-6 ratio showed significant inverse associations with SCC tumors, comparing higher tertiles with the lowest, in age- and sex-adjusted models (Ptrend = 0.02 and 0.03, respectively) which weakened after adjustment for past sun exposure. Associations between EPA and SCC were stronger among participants with a history of skin cancer at baseline (n = 378; highest vs. lowest tertile: RR = 0.50; 95% CI, 0.28-0.92; Ptrend = 0.01). Total omega-6 was inversely associated with BCC tumors in multivariate models (P = 0.04; highest vs. lowest tertile: RR = 0.71; 95% CI, 0.51-0.99), and more strongly in the subgroup with past skin cancer. Linoleic and linolenic acids were also inversely associated with BCC occurrence in this subgroup. When fatty acids were analyzed as continuous variables, however, there was no evidence of any linear or nonlinear associations. This study provides some support for reduced skin cancer risk with high plasma concentrations of omega-3 and omega-6 fatty acids, but results depended on how fatty acid data were modeled. Further investigation of these associations in larger datasets is needed.

Vitamin D may have anti-skin cancer effects, but population-based evidence is lacking. We therefore assessed associations between vitamin D status and skin cancer risk in an Australian subtropical community. We analyzed prospective skin cancer incidence for 11 years following baseline assessment of serum 25(OH)-vitamin D in 1,191 adults (average age 54 years) and used multivariable logistic regression analysis to adjust risk estimates for age, sex, detailed assessments of usual time spent outdoors, phenotypic characteristics, and other possible confounders. Participants with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) versus those below 75 nmol  l(-1) more often developed basal cell carcinoma (odds ratio (OR)=1.51 (95% confidence interval (CI): 1.10-2.07, P=0.01) and melanoma (OR=2.71 (95% CI: 0.98-7.48, P=0.05)). Squamous cell carcinoma incidence tended to be lower in persons with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) compared with those below 75 nmol  l(-1) (OR=0.67 (95% CI: 0.44-1.03, P=0.07)). Vitamin D status was not associated with skin cancer incidence when participants were classified as above or below 50 nmol  l(-1) 25(OH)-vitamin D. Our findings do not indicate that the carcinogenicity of high sun exposure can be counteracted by high vitamin D status. High sun exposure is to be avoided as a means to achieve high vitamin D status.

The QSkin Sun and Health Study comprises a cohort of 43 794 men and women aged 40-69 years randomly sampled from the population of Queensland, Australia in 2011. The cohort was established to study the development of skin cancer and melanoma in the population with the highest reported incidence of these diseases in the world. At baseline, besides demographic items and general medical history, information about standard pigmentary characteristics (including hair and eye colour, freckling tendency, tanning ability and propensity to sunburn), past and recent history of sun exposure and sunburns, sun protection behaviours, use of tanning beds and history of skin cancer was collected by self-completed questionnaire. Participants have given their consent for data linkage to the universal national health insurance scheme and for linkage to cancer registries and pathology databases, thus ensuring complete ascertainment of all future skin cancer and melanoma occurrences and medical treatments and other cancer events. Linkage to these registers will occur at predetermined intervals. Approval to access QSkin data can be obtained on application to the study investigators and submission of a formal research plan that has previous approval from the human research ethics committee of the applicant's institution.

Purpose: The 20-year survival rates are unknown for the majority of melanoma patients-those with thin melanomas. We determined 20-year survival rates of patients diagnosed with thin melanomas (≤ 1.00 mm) in the general population and also determined the main prognostic factors., Patients and Methods: Available clinical and histologic data from the Queensland Cancer Registry were obtained for all patients diagnosed with a single thin invasive melanoma from 1982 to 2006 and matched against national death registration data. Melanoma-specific survival estimates to December 31, 2007, were assessed, and subgroup differences in prognosis were determined by fitting multivariate Cox proportional hazard models., Results: Among 26,736 people in the state of Queensland diagnosed with thin melanomas, the 20-year survival was 96%. The most influential determinants of prognosis were tumor thickness ≥ 0.75 mm (adjusted hazard ratio [HR], 4.33; 95% CI, 2.8 to 6.8 compared with tumors < 0.25 mm) and patient age at diagnosis older than 65 years (HR, 2.8; 95% CI, 1.8 to 4.5) compared with age younger than 25 years. Acral lentiginous and nodular tumors, male sex, tumor site on the scalp or neck, or tumor invasion of the entire papillary dermis each independently increased the risk of dying from thin invasive melanoma., Conclusion: The outlook for patients with thin invasive melanoma is positive, although continued clinical vigilance is warranted for patients with nodular melanoma and those with the thickest tumors.

The objective of this study was to investigate the risk factors for melanoma on the arms and legs in comparison with well-known risk factors for trunk melanoma. The study was a population-based case-control study of 77 individuals with limb (25 arm; 52 leg) and 86 with trunk melanoma, who were representative of all the individuals newly-diagnosed with primary limb melanomas in Queensland during 1979-1980 and 232 controls. A single physician interviewed and examined all individuals and assessed complexion type, sun exposure history and other potential risk factors and clinical features. After multivariate analysis, the strongest risk factor for both limb and trunk melanomas was the presence of more than 10 naevi on the arm (odds ratio limb melanoma=41.4, 95% confidence interval 10.4-164), though on histology, a preexisting naevus was more strongly associated with trunk than limb melanoma (P<0.004). Associations with blonde/light brown hair, propensity to freckle and sunburn were similar for melanoma on both sites. A lifetime history of painful sunburns significantly raised the risk of trunk but not limb melanoma, whereas solar keratoses on the arm or face were more strongly associated with limb than with trunk melanoma (marginally significant, P(homogeneity)=0.056). High ambient solar ultraviolet radiation in adolescence was also a stronger risk factor for limb than for trunk melanoma. In conclusion, this population-based investigation into specific differences in causes of limb versus melanomas of other sites suggests that the risk factor profile is intermediate between the profiles for head/neck melanoma (mostly cumulative sun damage) and for trunk melanomas (most strongly related to naevi).

Objective: To investigate risk factors for lentigo maligna melanoma (LMM) compared with superficial spreading melanoma (SSM)., Design: Population-based case-control study in Queensland, Australia., Setting: General community., Participants: Population-based sample of 49 patients with LMM and 141 with SSM (in situ or invasive) aged 14 to 86 years at diagnosis in 1979 and 1980 and 232 control subjects. Response rates were 97.1% in cases and 91.8% in controls., Main Outcome Measures: Risks of both subtypes in relation to phenotypic and environmental factors, estimated by multinomial logistic regression., Results: The number of solar lentigines was the strongest determinant for LMM (odds ratio [OR], 15.93; P < .001 for trend) and significantly weaker for SSM (4.61; P < .001 for trend; P = .04 for homogeneity). Skin cancer history was significantly associated with LMM (OR, 2.84) but not with SSM (1.33; P = .07 for homogeneity). In contrast, the number of nevi was the strongest determinant for SSM (OR, 23.22; P < .001 for trend) while significantly weaker for LMM (3.60; P = .02 for trend; P < .001 for homogeneity). Multiple lifetime sunburns almost tripled the risk for SSM, whereas no association was detected with LMM (P = .04 for homogeneity). Shared risk factors for both subtypes were the number of solar keratoses (P < .001 for trend for both) and sun-sensitive complexion (ie, light eye/hair colors, sunburn propensity, and freckling) (2-fold to 5-fold increased risks)., Conclusions: A propensity to lentigines is a stronger predictor of LMM, whereas high nevus propensity is a stronger predictor of SSM. Skin cancer history appears to determine LMM risk only, whereas the number of lifetime sunburns determines SSM only. Prevention strategies could be tailored differently given these distinctive points of difference.

Intake of omega-3 and omega-6 fatty acids may modify the risk of basal and squamous cell carcinoma of the skin (BCC and SCC), but population-based evidence is limited and inconsistent. We examined prospectively associations between intake of omega-3 and omega-6 fatty acids estimated from food frequency questionnaires and BCC and SCC incidence among 1322 randomly selected adults in Nambour, Australia. Relative risks (RR) and 95% confidence intervals (CI) were estimated based on histologically confirmed tumors diagnosed between 1997 and 2007. Incidence of BCC was lowest in the middle third of both total omega-6 intake (RR(mv.adj) = 0.74, 95% CI = 0.56-0.97) and linoleic acid intake (RR(mv.adj) = 0.75, 95% CI = 0.57-0.99) compared with the lowest third of intake. Evidence for associations with SCC was weak, though persons with arachidonic acid intake in the middle third had a marginally increased risk of SCC (RR(mv.adj) = 1.42, 95% CI = 1.00-2.02). Consumption of omega-3 fatty acids was not associated with subsequent skin cancer risk. Suggestion that intake of arachidonic acid may be associated with increased SCC incidence and total omega-6 with reduced BCC from our study is still highly uncertain and may be due to chance. These data do not support an association between these fatty acids and risk of BCC or SCC.

Background: The relationship between physical activity and risk of cutaneous squamous cell carcinoma (SCC) is unknown and difficult to investigate due to confounding by sun exposure. We prospectively examined the association of recreational and occupational physical activity and incidence of SCC accounting for photoaging and other risk factors., Methods: We used available information on physical activity from the Australian population-based Nambour Skin Cancer Study comprising 1,171 adults aged 25-75 years at baseline (1992). In sex-stratified analyses (person-based and tumor-based) we estimated the associations between type of activity and incidence of SCC prospectively to 2007., Results: During 16 years of follow-up, 98 men and 90 women newly developed SCC. We found no significant association between recreational activity measures and SCC after controlling for potential confounding factors including indicators of sun exposure. In men, the observed risk pattern was however suggestive of elevated risk with increasing total hours of recreational activity (compared to inactive men, RR (95%CI) 0.89 (0.54, 1.46) for ≤ 1.5 hrs/wk; 1.29 (0.82, 2.04) for ≤ 4.0 hrs/wk; 1.33 (0.86, 2.05) > 4.0 hrs/wk), while among women, higher level of occupational activity (standing and manual versus sedentary work activities) was associated with a reduced incidence of SCC tumors (P trend = 0.03)., Conclusions: Despite some suggestion that recreational activity in men and occupational activity in women are related to occurrence of SCC, there is no firm support for a role of physical activity in the development of cutaneous SCC.

In this article, we will summarize some of the highlights of the third annual conference on skin cancer, with special emphasis on the the recent advances regarding melanoma and non-melanoma skin cancer epidemiology, diagnosis and treatment. Topics were particularly addressed to a newly developing medical branch in Australia, namely that of Primary Care Skin Cancer Practitioners, and focused on strategies to improve primary and secondary prevention and early detection of melanoma and non-melanoma skin cancer using dermoscopy. Controversies related to skin cancer screening programs and recent progresses for treating advanced melanoma were additionally discussed. Yet, besides its scientific goals, the conference aimed also to encourage research originating in primary care and relevant to primary care.