Risk Factor For Cutaneous Melanoma Research Articles

The potential impact of dietary choices on melanoma risk: an anti-inflammatory diet

The role of inflammation in the aetiology of cancer is recognized. However, no study yet examined the association between an anti-inflammatory diet and cutaneous melanoma and explored whether it could be modified by genetic variations in cyclooxygenase-2 (COX-2), a key enzyme in inflammation. A case-control study was conducted in the IDI-IRCCS hospital in Rome, Italy with 273 cases of primary cutaneous melanoma and 269 controls frequency matched to cases. Information on socio-demographic and pigmentary characteristics, medical history, sun exposure and dietary habits were collected for all subjects. The − 765G > C polymorphism was identified in DNA extracted from blood samples. An anti-inflammatory diet score was created. Logistic regression models were fitted to obtain odds ratios (ORs) and 95% confidence intervals (CIs). A high anti-inflammatory diet score (≥ 8 anti-inflammatory dietary items) was associated with a decreased risk of cutaneous melanoma (OR: 0.29; 95%CI: 0.17–0.49, Ptrend < 0.0001) after adjusting for sex, age, education, number of common nevi, skin photo-type, solar lentigines and sunburns in childhood. COX-2 -765 G > C polymorphism was not an independent risk factor for cutaneous melanoma. Although interaction between − 765G > C genotypes and anti-inflammatory diet score was not statistically significant (p = 0.25), when stratified by -765 G > C genotypes the effect of the anti-inflammatory diet was slightly more pronounced for participants carrying – 765GG (OR: 0.17; 95%CI: 0.06–0.47, Ptrend < 0.001). Our study findings suggest that adherence to an anti-inflammatory diet is associated with a decreased risk of developing cutaneous melanoma. These results suggest the potential impact of dietary choices on melanoma risk.

Clinical features and prognosis of cutaneous melanoma

Objective: To analyze the clinical features and prognosis of patients with cutaneous melanoma. Methods: The clinical data and follow-up data of 125 patients with cutaneous malignant melanoma (CMM) treated in the Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology between February 2008 and August 2019 were collected. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox proportional risk regression model was used for impact factor analysis. Results: Among the 125 patients, 12 were stage Ⅰ, 62 were stage Ⅱ, 30 were stage Ⅲ, and 21 were stage Ⅳ; 76 were acral and 49 were non-acral. The median survival time was 44 months, and the 1-, 2-, and 5-year survival rates were 85.4%, 63.2% and 38.7%, respectively. Kaplan-Meier univariate survival analysis showed that Karnofsky performance status score, tumor stage, primary site, vascular infiltration, Ki-67, BRAF, lactate dehydrogenase (LDH), and surgical treatment were related to the prognosis of patients (P<0.05). The median overall survival (OS) time of patients receiving interferon treatment was 53 months, which was better than 40 months of patients not receiving interferon treatment, but the difference was not statistically significant (P=0.448). Among stage Ⅲ patients, the median OS time of patients receiving interferon therapy was 40 months, which was better than 17 months of patients not receiving interferon therapy (P=0.012). Among stage Ⅱ patients, the 1-, 2-, and 5-year survival rates of acral patients were 97.1%, 84.7%, and 65.8%, and the 1-, 2-, and 5-year survival rates of non-acral patients were 93.3%, 70.0% and 17.0%. The prognosis of patients with stage Ⅱ acral type was better than that of non-acral type (P=0.043). The median survival time of stage Ⅲ patients with acral type was 32 months, better than 17 months of non-acral type, but the difference was not statistical significance (P=0.164). The median survival time of acral type and non-acral type was 8 months and 11 months respectively (P=0.458). Cox multivariate analysis showed that tumor stage and preoperative LDH level were independent prognostic risk factors for cutaneous melanoma. Conclusions: Interferon treatment can improve the prognosis of patients with stage Ⅲ, and stage Ⅱ acral type patients have better prognosis than that of non-acral type patients. Tumor stage and preoperative LDH level were independent prognostic risk factors for cutaneous melanoma.

Association of UV Radiation Exposure, Diagnostic Scrutiny, and Melanoma Incidence in US Counties

Although UV radiation exposure is the conventionally reported risk factor for cutaneous melanoma, an alternative exposure is diagnostic scrutiny: the more physicians look for and biopsy moles, the more melanoma they find. To assess the association of proxies for UV radiation exposure and diagnostic scrutiny with geographical patterns of melanoma incidence. This was a cross-sectional ecological analysis of the 727 continental US counties reporting to the Surveillance, Epidemiology, and End Results (SEER) Program (among a total of 3108 counties). Environmental data relevant to UV radiation exposure (from a variety of sources), Health Resources and Services Administration data relevant to diagnostic scrutiny, and SEER data on melanoma incidence among the non-Hispanic White population diagnosed with melanoma from 2012 through 2016 were combined. Data analysis was performed between January 2020 and July 2022. Three UV radiation proxies (UV daily dose, cloud variability, and temperature variability) and 3 diagnostic scrutiny proxies (median household income, dermatologists, and primary care physician supply). Melanoma incidence (in situ and invasive cancers). In total, 235 333 melanomas were diagnosed. Proxies for UV radiation exposure changed gradually across geography, while melanoma incidence and proxies for diagnostic scrutiny changed abruptly across contiguous counties. The UV daily dose, a variable the National Cancer Institute specifically developed for melanoma analyses, was uncorrelated with incidence (r = 0.03; P = .42). For context, smoking prevalence was highly correlated with lung cancer incidence in the same counties (r = 0.81; P < .001). Melanoma incidence was correlated with median household income (r = 0.43; P < .001). Counties with no dermatologists and shortages of primary care physicians had the lowest incidence, while counties amply supplied with both had the highest, despite having lower mean UV daily dose. There was little association between melanoma incidence and melanoma mortality (r = 0.09; P = .05), while the analogous association in lung cancer was strong (r = 0.96; P < .001). In this cross-sectional ecological study, the current geographical pattern of melanoma incidence across US counties was less associated with proxies for UV radiation exposure and more so with proxies for diagnostic scrutiny. Incidence-the fundamental epidemiologic measure of disease frequency-now had little association with the feared outcome of melanoma: death.

Melanoma-specific survival before and after inclusion in a familialmelanoma dermatologic surveillance program in CDKN2A mutation carriers and non-carriers.

Inherited mutations in the CDKN2A gene are among the strongest known risk factors for cutaneous melanoma. Further, previous studies have reported inferior melanoma-specific survival in CDKN2A mutation carriers. Here, the melanoma-specific survival was studied, depending on CDKN2A carrier status and if the melanomas had been diagnosed before or after families were included in a surveillance program. Melanoma-prone families participating in this study were identified through a nationwide preventive program starting in 1987. Information on melanoma tumours and deaths was obtained through the Swedish Cancer Registry and Cause of Death Registry. Kaplan-Meier and Cox proportional hazards regression models were used to assess melanoma-specific survival in four defined cohorts, CDKN2A mutation (MUT) carriers with first invasive melanoma before or after inclusion [MUT-pre (n=53) and MUT-post (n=43)] and likewise in CDKN2A wild type (WT) cases [WT-pre (n=255) and WT-post (n=122)]. The MUT-pre and MUT-post cases were diagnosed with their first invasive melanoma at a significantly younger ages (38 and 42 years, respectively) than the WT-pre and WT-post cases (48 and 57 years, respectively). The melanomas in the MUT-pre had significantly higher T stage compared with MUT-post (p=0.006), whereas no such difference was seen comparing WT-pre with WT-post (p=0.849). MUT-pre had compared with WT-pre, significantly worse melanoma-specific survival, unadjusted (HR 2.33, 95% CI 1.33-4.08, p=0.003) adjusted (HR 2.70, 95% CI 1.46-5.00, p=0.001). However, the MUT-post cases had compared with the WT-post cases, no significant survival differences. This study is the first to address the impact on survival from introducing a dermatologic surveillance program to familial melanoma cases with or without CDKN2A mutations. The CDKN2A-mut carriers appeared to have a clear benefit with less advanced melanomas diagnosed and better melanoma-specific survival after inclusion. Among the CDKN2A-wt cases, the effect of the inclusion on the studied outcomes was less evident.

Self-Assessment Questionnaire on Patient-Physician Concordance on Nevus Self-Count and Models Development to Predict High-Risk Phenotype >50 Nevi

Background: Cutaneous melanoma accounts for the majority of skin cancer-related deaths. Readily identifiable phenotypic characteristics and total body nevus count (TBNC) >50 are among the most important risk factors for cutaneous melanoma. Implementation of nevus self-count procedures and self-assessment of phenotypic traits as part of skin self-examination could be an excellent screening tool for identifying an at-risk target population. Objectives: Objectives of the study were to assess the skills of a central Italian and eastern Spanish population sample to recognize their skin lesions via the submission of a self-assessment questionnaire and to explore which self-assessment questionnaire item combination best predicts the high-risk condition of TBNC >50. Methods: Patients aged ≥18 years filled a self-assessment questionnaire, autonomously and prior to the dermatological visit. Subsequently, dermatologists performed total body skin examination and reported patients’ skin lesions on a separate questionnaire. Results: We reported fair to moderate patient-dermatologist agreement for skin lesion self-assessment. The item number of nevi on the back was the single questionnaire item most accurately predicting TBNC >50. The high-sensitivity and high-specificity classification and regression tree models for the prediction of TBNC >50 displayed different items combinations; the item nevus on the back was always the first and most important predictor in both our models. Conclusions: Patients were partially able to provide correct estimation of their whole-body nevus self-count. The item nevi on the back seems to be the first and most important predictor of TBNC >50 across our models. Delivery of high-sensitivity and high-specificity prediction models based on our questionnaire item combination may help defining a high-risk target population.

Ambient UVR and Environmental Arsenic Exposure in Relation to Cutaneous Melanoma in Iowa.

Intermittent sun exposure is the major environmental risk factor for cutaneous melanoma (CM). Cumulative sun exposure and other environmental agents, such as environmental arsenic exposure, have not shown consistent associations. Ambient ultraviolet radiation (UVR) was used to measure individual total sun exposure as this is thought to be less prone to misclassification and recall bias. Data were analyzed from 1096 CM cases and 1033 controls in the Iowa Study of Skin Cancer and Its Causes, a population-based, case-control study. Self-reported residential histories were linked to satellite-derived ambient UVR, spatially derived environmental soil arsenic concentration, and drinking water arsenic concentrations. In men and women, ambient UVR during childhood and adolescence was not associated with CM but was positively associated during adulthood. Lifetime ambient UVR was positively associated with CM in men (OR for highest vs. lowest quartile: 6.09, 95% confidence interval (CI) 2.21–16.8), but this association was not as strong among women (OR for highest vs. lowest quartile: 2.15, 95% CI 0.84–5.54). No association was detected for environmental soil or drinking water arsenic concentrations and CM. Our findings suggest that lifetime and adulthood sun exposures may be important risk factors for CM.

Differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents.

It is not known if children and adolescents with atypical Spitz tumour and cutaneous melanoma differ in terms of etiological factors. The aim of this study was to explain differences in individual and environmental factors between cutaneous melanoma and atypical Spitz tumour. In the context of a study on melanocytic lesions, all subjects aged under 20years with either cutaneous melanoma or atypical Spitz tumour were included (N = 105). Information on socio-demographic characteristics, individual and environmental factors were collected for both mother and child. The Fisher's exact test and the Mann-Whitney U test were used for categorical variables and continuous variables respectively. A multivariate logistic model was used to explain differences in outcome by differences in explanatory variables. In comparison to patients with cutaneous melanoma, patients with atypical Spitz tumour had less freckles (p = 0.020), lower number of common nevi (p = 0.002), and lower body mass index (p = 0.001) and experienced less sunburns episodes (p = 0.008). However, in the multivariate analysis, only a low number of common nevi remained statistically significant. Children and adolescents with cutaneous melanoma have a high number of nevi in comparison to the same-age group with atypical Spitz tumour.Conclusion: The results of this study suggest that the only difference in individual and environmental risk factors between cutaneous melanoma and atypical Spitz tumour in children and adolescents is the number of nevi. What is Known: •Atypical Spitz tumours and cutaneous melanoma in children and adolescents are clinically similar, but compared with melanoma, they have a good overall prognosis. •Risk factors for cutaneous melanoma in children and adolescents are similar to the ones found in adults in the literature What is New: •Differences in individual and environmental risk factors for atypical Spitz tumour in children and adolescents are described for the first time in this study. •Individual and environmental factors for atypical Spitz tumour in children and adolescents are comparable to cutaneous melanoma, except for the presence of low number of nevi.

A narrative review on the outcome of primary cutaneous melanomas arising in solid organ transplant recipients.

Chronic immunosuppression is a risk factor for cutaneous melanoma, as indicated by the increased incidence among solid organ transplant recipients (OTRs). The outcome of post-transplant melanomas has not frequently been investigated. The aim of this narrative review was to investigate overall survival (OS) and melanoma-specific mortality (MSM) of primary cutaneous melanomas (CM) among OTRs compared to the outcome of cutaneous melanomas arising in immunocompetent patients. A systematic literature search was conducted in PubMed to identify studies reporting on primary CM among OTRs and their outcome. The search was restricted to the English language and included investigations through to April 1st, 2019. Of the seven articles included, all except one reported a lower OS for primary CM among OTRs compared to immunocompetent patients. In these six investigations, MSM was increased, but not relative to Clark level, Breslow thickness or American Joint Committee on Cancer (AJCC) stage. A lower OS can be expected among OTRs with primary CM. There is still much heterogeneity in MSM adjusted for Breslow thickness, AJCC staging and Clark level, with no conclusive answers. Prospective studies are needed to clarify MSM for this specific patient group.

Efficacy of BRAF and MEK Inhibition in Patients with BRAF-Mutant Advanced Melanoma and Germline CDKN2A Pathogenic Variants.

Simple SummaryIn our study, we retrospectively collected data of patients with germline CDKN2A pathogenic variants who received targeted therapy for advanced melanoma across four European centers. Since loss of CDKN2A function may intrinsically limit the activity of MAPK-directed targeted therapy, we decided to assess whether patients with germline CDKN2A pathogenic variants may achieve suboptimal results with BRAF and MEK inhibitors. To the best of our knowledge, this is the first study reporting on patients with BRAF-mutant advanced melanoma and a germline CDKN2A pathogenic variant who received treatment with BRAF with or without MEK inhibitors. Despite the limitations of our study, mostly due to the rare frequency of CDKN2A pathogenic variants, a challenge for the conduction of prospective trials with proper sample size, our results support treatment with targeted therapy in this subset of patients.Inherited pathogenic variants (PVs) in the CDKN2A tumor suppressor gene are among the strongest risk factors for cutaneous melanoma. Dysregulation of the p16/RB1 pathway may intrinsically limit the activity of MAPK-directed therapy due to the interplay between the two pathways. In our study, we assessed, for the first time, whether patients with germline CDKN2A PVs achieve suboptimal results with BRAF inhibitors (BRAFi)+/−MEK inhibitors (MEKi). We compared the response rate of nineteen CDKN2A PVs carriers who received first-line treatment with BRAFi+/−MEKi with an expected rate derived from phase III trials and “real-world” studies. We observed partial response in 16/19 patients (84%), and no complete responses. The overall response rate was higher than that expected from phase III trials (66%), although not statistically significant (p-value = 0.143; 95% CI = 0.60–0.97); the difference was statistically significant (p-value = 0.019; 95% CI = 0.62–0.97) in the comparison with real-world studies (57%). The clinical activity of BRAFi+/−MEKi in patients with germline CDKN2A PV was not inferior to that of clinical trials and real-world studies, which is of primary importance for clinical management and genetic counseling of this subgroup of patients.

CDKN2A genetic testing in melanoma-prone families in Sweden in the years 2015–2020: implications for novel national recommendations

Background: Inherited pathogenic variants (PVs) in the CDKN2A gene are among the strongest known risk factors for cutaneous melanoma. Carriers are at high risks to develop multiple primary melanomas and other cancers, in particular pancreatic cancer. In this study, the CDKN2A testing, carried out in Sweden in the years 2015–2020, was evaluated. Materials and methods: Included families had (1) three or more cases of melanoma and/or pancreatic cancer, (2) two melanomas in first-degree relatives, the youngest case <55 years or (3) individuals with three or more multiple primary melanomas, the first before the age of 55 years, and no other affected family members. The included families had at least one affected member that had been tested for CDKN2A PVs. Results: In total, 403 families were included, whereof 913 family members had been diagnosed with cutaneous melanoma and 129 with pancreatic cancer, 33 (8.2%) were found to have PVs in CDKN2A. Frequencies ranged from 0.9% in families with only two melanomas to 43.2% in families with three or more melanoma cases and pancreatic cancer (p < 0.001). The frequency of PVs ranged from 2.1% to 16.5% in families where the youngest case was ≥55 years or <35 years (p = 0.040). In families with or without CDKN2A PVs, 37.6% and 10.0% had melanoma cases that had died from melanoma, respectively (p < 0.001). Discussion: Significant differences were seen in the frequencies of CDKN2A PVs, dependent on numbers or age at diagnosis of melanomas and diagnoses of pancreatic cancers in the family. Further, melanoma cases belonging to families that tested positive for CDKN2A PVs had a significantly higher mortality. To summarize, the current evaluation shows that, with adequately selected criteria to guide genetic testing, CDKN2A PVs are identified at significant frequencies. Identification of carrier families is of importance to ensure that members are enrolled in a preventive surveillance program.

Challenges and Controversy in Determining UV Exposure as a Risk Factor for Cutaneous Melanoma in Skin of Color

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Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population

Ultraviolet light exposure and cutaneous pigmentation are important host risk factors for cutaneous melanoma (CM), and it is well known that inherited ability to produce melanin varies in humans. The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. ADCY3 c.675+9196T>G, CREB1 c.303+373G>A, and MITF c.938-325G>A were selected for data validation among 74 SNVs. Individuals with CREB1 GA or AA genotype and allele “A” were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of CREB1 AA and MITF AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with ADCY3 TT had 1.89 more chances of presenting CM progression, and those with MITF GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in ADCY3, CREB1, and MITF pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients’ clinicopathological features.

Serum Total 25-Hydroxyvitamin D Levels in Patients With Cutaneous Malignant Melanoma: A Case-Control Study in a Low-Risk Southern European Population.

Recent data have shown an inverse association between serum 25-hydroxyvitamin D concentration and incidence of several cancers, including cutaneous malignant melanoma (CMM). In addition, lower serum 25-hydroxyvitamin D levels have been associated with thicker or higher stage melanomas and worse survival in observational studies. Ninety-nine patients diagnosed with primary CMM and 97 matched healthy controls entered the study. Demographic characteristics, risk factors for CMM, and clinical and histological characteristics were recorded for patients with primary CMM. Total serum 25-hydroxyvitamin D levels of melanoma patients measured by fully automated chemiluminescent vitamin D total immunoassay (Elecsys vitamin D total, Roche) at the time of diagnosis were compared with those of healthy controls. In addition, we tested the association of serum total 25-hydroxyvitamin D levels at melanoma diagnosis with known risk and prognostic factors for CMM. Of the melanoma patients, 49 (49.49%) had deficient serum total 25-hydroxyvitamin D levels (<20 ng/mL), 23 (23.23%) had insufficient levels (21-29 ng/mL), and 27 (27.27%) had adequate levels (>30 ng/mL). The median serum total 25-hydroxyvitamin D levels were significantly lower in melanoma patients (20.62 ng/mL) compared with healthy controls (24.71 ng/mL), but statistical significance was not reached (chi-square test, P = 0.051) No statistically significant association was found between serum total 25-hydroxyvitamin D levels and demographic characteristics; risk factors for CMM; prognostic factors, such as Breslow thickness and ulceration; as well as clinical characteristics, such as melanoma stage, clinical type, and location. Lower serum 25-hydroxyvitamin D levels were found in our Greek cohort of melanoma patients compared with healthy controls, without reaching, however, statistical significance; these levels were not statistically associated with established risk and prognostic factors for CMM.

Insulin Resistance as a Risk Factor for Cutaneous Melanoma. A Case Control Study and Risk-Assessment Nomograms.

Insulin resistance and obesity are suggested to have a key role in the molecular pathogenesis of various disorders, including several malignancies. Moreover, insulin resistance has recently been found to be associated with cutaneous and uveal melanoma, while a variable positive correlation between obesity and the risk of cutaneous melanoma was also found at least in men. The present trial aims at confirming whether insulin resistance, assessed with the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI), is a risk factor for cutaneous melanoma. One hundred and thirty patients diagnosed with cutaneous melanoma and 130 age-, sex-, and skin phototype-matched controls were evaluated. At the univariate and multivariate analysis, the diagnosis of cutaneous melanoma was inversely related with insulin resistance (HOMA-IR) and positively with BMI (p = 0.0014 and p = 0.008, respectively). Consistently, insulin sensitivity (QUICKI) and BMI resulted positively associated with the diagnosis of cutaneous melanoma (p = 0.0001 and p = 0.0026, respectively). The results obtained are partially in agreement with those reported in the literature. By comparing our data with those generated by other studies, inconsistencies in key features among subgroups of different trials have emerged, possibly affecting final correlations. Based on insulin resistance/sensitivity, fasting insulinemia/glycemia, and BMI values collected from patients who participated in the present trial, two nomograms potentially assessing the risk of cutaneous melanoma have been generated. Molecular aspects sustain a role for insulin resistance in the carcinogenesis of cutaneous melanoma, but clinical data remain uncertain. Larger, well-balanced, correlative trials are still needed to define the potential role of insulin resistance in the carcinogenesis of cutaneous melanoma.

Melanoma risk stratification of individuals with a high-risk naevus phenotype - A pilot study.

High a naevus counts and atypical naevi are risk factors for cutaneous melanoma. However, many individuals with a high-risk naevus phenotype do not develop melanoma. In this study, we describe the clinical and dermoscopic attributes of naevi associated with melanoma in a high-risk naevus phenotype population. This single-centre, hospital-based case-control study included 54 prospectively enrolled adult patients ≥18 years old with a high-risk naevus phenotype (18 cases with a history of melanoma and 36 age- and gender-matched controls without a history of melanoma). We analysed clinical and dermoscopic images of the 20 largest naevi for each participant. Cases had a higher mean age than controls (48.2 vs. 39.1 years, P = 0.007) but there was no difference in the male-to-female ratio between groups. Nearly, all participants (97%) were Fitzpatrick skin type II or III. Naevi in cases were more likely to be truncal, (72.6% vs. 53.6%, P = 0.01), particularly anterior truncal, (29.2% vs. 14.4%, P < 0.001) and larger than 8 mm (17.4% vs. 7.8%%, P = 0.01) compared to controls. CASH score of naevi did not differ between groups. Naevi in cases were more likely to have a multicomponent dermoscopic pattern than in controls (18.4% vs. 12.6%, P = 0.02). Larger naevi, truncal naevi, and naevi, with a multicomponent dermoscopic pattern may be risk factors for melanoma among individuals with a high-risk naevus phenotype. Further studies are needed to validate these findings.

Global burden of cutaneous melanoma attributable to ultraviolet radiation in 2012.

Ultraviolet radiation (UVR) is a strong and ubiquitous risk factor for cutaneous melanoma, emitted naturally by the sun but also artificial sources. To shed light on the potential impact of interventions seeking to reduce exposure to UVR in both high and low risk populations, we quantified the number of cutaneous melanomas attributable to UVR worldwide. Population attributable fractions and numbers of new melanoma cases in adults due to ambient UVR were calculated by age and sex for 153 countries by comparing the current melanoma burden with historical data, i.e., the melanoma burden observed in a population with minimal exposure to UVR. Secondary analyses were performed using contemporary melanoma incidence rates in dark-skinned African populations with low UVR susceptibility as reference. Globally, an estimated 168,000 new melanoma cases were attributable to excess UVR in 2012, corresponding to 75.7% of all new melanoma cases and 1.2% of all new cancer cases. This burden was concentrated in very highly developed countries with 149,000 attributable cases and was most pronounced in Oceania, where 96% of all melanomas (representing 9.3% of the total cancer burden) were attributable to excess UVR. There would be approximately 151,000 fewer melanoma cases worldwide were incidence rates in every population equivalent to those observed in selected low-risk (dark-skinned, heavily pigmented) reference populations. These findings underline the need for public health action, an increasing awareness of melanoma and its risk factors, and the need to promote changes in behavior that decrease sun exposure at all ages.

High serum vitamin D level correlates with better prognostic indicators in primary melanoma: A pilot study.

Sunlight is a major risk factor for cutaneous melanoma. However, its interaction with melanoma is complex. In particular, vitamin D is a UVB-derived hormone that has been shown to have anti-cancer effects. In this retrospective pilot study we sought to determine an association between the clinicopathological features of melanoma and the patients' corresponding serum vitamin D level. In total, 109 primary melanomas diagnosed between 2001 and 2013 were retrospectively identified from our institutional database with a corresponding 25-hydroxyvitamin D3 level estimated within 6 months of diagnosis. Tumour, clinical (age, sex, tumour location) and pathological (thickness, mitosis, ulceration, Clark level, subtype, metastatic status) parameters were correlated with vitamin D. For statistical analysis, an unpaired Student's t-test and anova was used for categorical variables, and Spearman's correlation for continuous variables. Vitamin D level was inversely associated with Breslow thickness as a dichotomous, categorical and continuous variable. The association remained significant when controlled for patient's age and sex (P = 0.026). Vitamin D was higher in non-ulcerated tumours compared with ulcerated tumours (P = 0.006) and in tumours with mitotic rate <1/mm2 compared with ≥1/mm2 (P = 0.036). A significant association was found between vitamin D level and tumour histological subtype (P = 0.019). On subgroup analysis, significant associations were found between superficial spreading melanoma (SSM) and nodular melanoma (P = 0.026), and SSM and acral lentiginous melanoma (P = 0.007). A high vitamin D status may benefit prognosis in patients diagnosed with primary melanoma. A prospective cohort analysis with a large sample and controlled for other vitamin D confounders would validate these findings.

BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy.

Objective: To investigate whether vitamin D receptor gene (VDR) BsmI-rs1544410 and FokI-rs2228570 polymorphisms, smoking duration, and body mass index (BMI) are risk factors for cutaneous melanoma, especially metastatic melanoma. Methods: We studied 120 cutaneous melanoma cases [68 stage I and II non-metastatic melanoma (NMetM) patients, plus 52 Stage III and IV metastatic melanoma (MetM) patients], and 120 matching healthy controls from northeast Italy. VDR polymorphisms were measured by restriction fragment length polymorphism analysis. Absence or presence of BsmI and FokI restriction sites was denoted by " B” and " F” or by " b” and " f,” respectively. Results: VDR-BsmI bb genotype was more frequent among MetM (32.7%) than among NMetM cases (13.2%), with odds ratio (OR)=3.18. Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.43); ≥20 years of smoking combined with bb (OR=4.78), Bb+bb (OR=2.30), Ff (OR=3.04), and Ff+ff (OR=3.08); obesity (BMI>30 kg/m2) alone (OR=3.54); and obesity combined with Bb+bb (OR=3.52), Ff (OR=4.78), and Ff+ff (OR=6.56). Comparison of MetM vs NMetM patients revealed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.39), ≥20 years of smoking combined with bb (OR=5.13), Bb+bb (OR=3.07), and Ff+ff (OR=2.66); and obesity combined with Bb+bb (OR=5.27), Ff (OR=6.28), and Ff+ff (OR=9.18). Triple combination of ≥20 years of smoking, obesity, and Bb+bb yielded OR=9.65 for melanoma patients vs healthy controls and OR=12.2 for MetM vs. NMetM patients. Conclusions: Risk factors for cutaneous MetM include two VDR polymorphisms combined with smoking duration and obesity. Results suggest gene-environment implications in melanoma susceptibility and severity. Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.

Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma

Background:The rate of interval cancers is an established indicator for the performance of a cancer-screening programme.Methods:We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4–24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999–2002), extracted from the cancer registry.Results:The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82–1.05; in situ: 1.61 (1.32–1.95), invasive: 0.71 (0.60–0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent.Interpretation:The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

Non-genetic risk factors for cutaneous melanoma and keratinocyte skin cancers: An umbrella review of meta-analyses

BackgroundSkin cancers have a complex disease mechanism, involving both genetic and non-genetic risk factors. Numerous meta-analyses have been published claiming statistically significant associations between non-genetic risk factors and skin cancers without applying a thorough methodological assessment. ObjectiveThe present study maps the literature on the non-genetic risk factors of skin cancers, assesses the presence of statistical biases and identifies the associations with robust evidence. MethodsWe searched PubMed up to January 20, 2016 to identify systematic reviews and meta-analyses of observational studies that examined associations between non-genetic factors and skin cancers. For each meta-analysis, we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We also assessed the between-study heterogeneity (I2 metric), evidence for small-study effects and excess significance bias. ResultsForty-four eligible papers were identified and included a total of 85 associations. Twenty-one associations were significant at P<10−6. Fifty-two associations had large or very large heterogeneity. Evidence for small-study effects and excess significance bias was found in fifteen and thirteen associations, respectively. Overall, thirteen associations (actinic keratosis, serum vitamin D, sunburns, and hair color for basal cell carcinoma and density of freckles, eye color, hair color, history of melanoma, skin type, sunburns, premalignant skin lesions, common and atypical nevi for melanoma) presented high level of credibility. ConclusionThe majority of meta-analyses on non-genetic risk factors for skin cancers suffered from large between-study heterogeneity and small-study effects or excess significance bias. The associations with convincing and highly suggestive evidence were mainly focused on skin photosensitivity and phenotypic characteristics.