Risk Factor For Melanoma Research Articles

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.

Sunlamp use is a risk factor for uveal melanoma: a meta-analysis

ObjectiveAdvancements in the treatment of uveal melanoma have not improved survival; therefore, identifying modifiable risk factors is critical to improving outcomes. This study aims to investigate the association between sunlamp use and the development of uveal melanoma. DesignThis study is designed as a meta-analysis. MethodsLiterature was searched and reviewed through the MEDLINE (with both OVID and PubMed), EMBASE, MD Consult, and Web of Science databases. These databases were searched from 1966 to 2019 using the following keywords to identify articles examining risk factors for uveal melanoma: ultraviolet, sun, sunlight, uveal melanoma, eye cancer, eye melanoma, nevus, and risk factor. All articles were evaluated for inclusion based on methodology and data reporting association between sunlamp use and uveal melanoma. The Meta-analysis of Observational Studies in Epidemiology guidelines and the Newcastle-Ottawa Scale were used to assess data quality and validity. A random effects model was employed. ResultsA total of 5 studies, enrolling a total of 1753 uveal melanoma cases and 3399 controls were included in this meta-analysis. The results of this study showed a positive association between sunlamp use and uveal melanoma (odds ratio = 2.15; 95% confidence interval 1.27–3.64). Meta-regression of between study heterogeneity did not reveal a statistically significant association when publication year, site latitude, melanoma tissue location (specifically, inclusion of iris tumors), or control type (population versus clinic) were evaluated. ConclusionThis meta-analysis identified a statistically significant association between sunlamp use and uveal melanoma, supporting sunlamp use as a modifiable risk factor for uveal melanoma.

Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity<0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity=0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

Melanoma and the Gastrointestinal (GI) Tract: Maintaining a High Index of Suspicion

Malignant melanoma is a life-threatening malignant tumor deriving from melanocytes, regarded as the most lethal form of skin cancer. One of the attributing factors to this fact is its propensity to metastasize to all organs of the human body. The strongest risk factors for melanoma include exposure to UV rays, family history of melanoma, and a prior history of melanoma. Malignant melanoma is thought to metastasize first to the local lymph nodes and then to secondary sites, most commonly skin, lung, and to the brain. This case highlights the severity of melanoma and its negative impact on the gastrointestinal tract. Patients with metastatic melanoma to the gastrointestinal tract can present with nonspecific, generalized gastrointestinal symptoms such as abdominal pain or constipation. Here we discuss the pathology, symptomatology, management options, and prognosis of metastatic melanoma of the gastrointestinal tract. The aim of this case is to promote a high index of suspicion of gastrointestinal metastasis in melanoma patients with gastrointestinal symptoms.

Association between melanoma and exposure to sex hormones in puberty: A possible window of susceptibility (Review)

The risk factors for melanoma in adolescents are similar to those in adults; however, it remains unclear whether these risk factors are also associated with melanoma in children. Epidemiological studies in the literature have reported a logarithmic increase in melanoma incidence after the age of 10 years. This may, in part, reflect the acute and chronic exposure to solar ultraviolet (UV) radiation during childhood. However, it appears unlikely that the cumulative exposure to UV radiation alone could explain such a sharp increase in melanoma incidence at the beginning of adolescence. It has been suggested that circulating sex hormones, the levels of which increase during puberty, may play a role in melanoma initiation and progression in predisposed individuals through binding to specific sex steroid receptors. The association between a longer cumulative exposure to sex hormones and the risk of melanoma may be supported by the reported epidemiological association between melanoma and several other sex hormone-related types of cancer, such as breast and prostate cancer, in which the enhanced exposure to androgens and estrogens was found to be directly associated with pubertal onset. Therefore, determining the association between pubertal onset and melanoma development may improve the current understanding of melanoma pathophysiology.

Low sun exposure habits is associated with a dose-dependent increased risk of hypertension: a report from the large MISS cohort

In prospective observational cohort studies, increasing sun exposure habits have been associated with reduced risk of cardiovascular mortality. Our aim was to assess possible observational mechanisms for this phenomenon. A written questionnaire was answered by 23,593 women in the year 2000 regarding risk factors for melanoma, including factors of possible interest for hypertension, such as detailed sun exposure habits, hypertension, marital status, education, smoking, alcohol consumption, BMI, exercise, and chronic high stress. Hypertension was measured by the proxy “use of hypertension medication” 2005–2007, and high stress by “need of anti-depressive medication”. Sun exposure habits was assessed by the number of `yes’ to the following questions; Do you sunbath during summer?, During winter vacation?, Do you travel south to sunbath?, Or do you use sun bed? Women answering ‘yes’ on one or two questions had moderate and those answering ‘yes’ on three or four as having greatest sun exposure. The main outcome was the risk of hypertension by sun exposure habits adjusted for confounding. As compared to those women with the greatest sun exposure, women with low and moderate sun exposure were at 41% and 15% higher odds of hypertension (OR 1.41, 95% CI 1.3‒1.6, p < 0.001 and OR 1.15, 95% CI 1.1‒1.2, p < 0.001), respectively. There was a strong age-related increased risk of hypertension. Other risk factors for hypertension were lack of exercise (OR 1.36), a non-fair phenotype (OR 1.08), chronic high stress level (OR 1.8), and lack of university education (OR 1.3). We conclude that in our observational design sun exposure was associated with a dose-dependent reduced risk of hypertension, which might partly explain the fewer deaths of cardiovascular disease with increasing sun exposure.

Melanoma Prevention: Comparison of Different Screening Methods for the Selection of a High Risk Population.

Background: Guidelines recommend limiting melanoma screening in a population with known risk factors, but none indicates methods for efficient recruitment. The purpose of this study is to compare three different methods of recruiting subjects to be screened for melanoma to detect which, if any, is the most efficient. Methods: From 2010 to 2019, subjects were recruited as follows: (1) regular skin examinations (RS), mainly conducted through the Associazione Contro il Melanoma network; (2) occasional melanoma screening (OS), during annual public campaigns; (3) and selective screening (SS), where people were invited to undergo a skin check after filling in a risk evaluation questionnaire, in cases where the assigned outcome was intermediate/high risk. Melanoma risk factors were compared across different screening methods. Generalized Linear Mixed Models were used for multivariable analysis. Results: A total of 2238 subjects (62.7% women) were recruited, median age 44 years (2–85), and 1094 (48.9 %) records were collected through RS, 826 (36.9 %) through OS, and 318 (14.2 %) through SS. A total of 131 suspicious non-melanoma skin cancers were clinically diagnosed, 20 pathologically confirmed, and 2 melanomas detected. SS performed significantly better at selecting subjects with a family history of melanoma and I-II phototypes compared to OS. Conclusions: Prior evaluation of melanoma known risk factors allowed for effective selection of a population to screen at higher risk of developing a melanoma.

Validation of the “knowledge about melanoma early detection scale” in a sample of melanoma survivors

The purpose of this study was to describe the development and preliminary testing of a new scale assessing knowledge about melanoma risk factors and early detection/secondary prevention. Data was drawn from a longitudinal study assessing barriers and facilitators of skin self- examination among patients diagnosed with melanoma. For the current analysis, 191 patients who completed the new 9-item Knowledge About Melanoma Early Detection Scale and other study measures were included. Exploratory factor analysis with were conducted, which identified a robust scale comprised of 6 items with factor loadings ranging from .56 to .81. Higher scores on the Knowledge About Melanoma Early Detection Scale were associated with younger age and more positive attitudes about melanoma prevention, but not with biological sex, education, melanoma stage, or past self-administered and physician-provided skin checks. Further studies are needed to replicate these findings and to further establish the predictive validity of this scale and its usefulness for health research.

Higher susceptibility to sunburn is associated with decreased plasma glutamine and increased plasma glutamate levels among US women: An analysis of the Nurses' Health Study I and II

Higher susceptibility to sunburn is associated with decreased plasma glutamine and increased plasma glutamate levels among US women: An analysis of the Nurses' Health Study I and II

Risk factors for thick melanoma among veterans: A cross-sectional study

Risk factors for thick melanoma among veterans: A cross-sectional study

Frequency of Trauma, Physical Stress, and Occupation in Acral Melanoma: Analysis of 313 Acral Melanoma Patients in Korea.

BackgroundTraumatic events are thought to be a cause of acral melanoma. However, little is known about the role of mechanical trauma or physical stress in the development of acral melanoma.ObjectiveIn our study, we evaluated the frequency of trauma, physical stress, and occupation in patients with acral melanoma and aimed to identify any pathological correlates of these factors.MethodsWe conducted a retrospective study of 313 acral melanoma patients from Chonnam National University Hospital. We mapped melanoma-developed anatomical sites of acral areas and assessed patients' history of trauma, physical stress, and occupation.ResultsAmong the 313 acral melanoma patients, many reported a traumatic event (84 of 313; 26.8%) or physical stress (91 of 313; 29.1%) before the melanoma developed. The most common anatomical sites in these patients were on the borders of the foot (136 of 313; 43.5%). Trauma was more commonly associated with the fingernails and toenails than other sites. The frequency of each type of physical stress depended on the site of the lesion. Farmer and fisherman were the most common occupations (130 of 313; 41.5%) of the acral melanoma patients.ConclusionOur results demonstrate that traumatic events, physical stress, and certain occupations are common in acral melanomas. Further studies are needed to establish whether these are risk factors for acral melanomas.

Cul4b Promotes Progression of Malignant Cutaneous Melanoma Patients by Regulating CDKN2A

Although several molecular targeted therapy and immunotherapy have been developed, cutaneous melanoma prognosis is still not satisfying. Cul4b promotes the progression of several malignant tumors by regulating cell proliferation. However, its prognostic role in malignant cutaneous melanoma has not been evaluated. In this study, immunohistochemistry was performed to assess the expression of Cul4b in a consecutive patient cohort. The prognostic role of Cul4b was estimated with univariate and multivariate analysis. Cul4b was knocked down in melanoma cell line to evaluate its role in promoting cell proliferation. The results revealed that Cul4b was highly expressed in some of the cutaneous malignant melanoma patients and high expression of Cul4b was associated with poor melanoma-specific overall survival and poor disease-free survival. Cul4b expression was associated with Breslow categories, Clark level, and Ki67 expression. Univariate and multivariate analysis revealed that Cul4b is an independent prognosis risk factor of cutaneous melanoma. Downregulation of Cul4b inhibited the proliferation ability of melanoma cells and downregulated the expression of CDKN2A. These results suggest that Cul4b plays an essential role in cutaneous melanoma progression and may serve as a promising treatment target.

Semi-automated total body photography supports robust delivery of skin cancer monitoring services during the SARS-COV2/COVID-19 pandemic

The SARS-CoV-2/COVID-19 pandemic dramatically impacted the delivery of healthcare, including dermatological services. In the initial stages of the pandemic, reduced patient flow produced a dramatic drop in the volume of skin cancer screening. Consistent with COVID-19 precautions, our practice conducted visual skin examinations (VSE) utilizing semi-automated total body photography (TBP). A cross-sectional study of patient characteristics and self-reported melanoma risk factors associated with TBP usage was conducted on all patients from May to November 2020 in a single practitioner private dermatology setting. The process and histopathology-confirmed outcomes were compared to those in the same 6-month period in 2019. For the May-November 2020 timeframe, those who opted for the home TBP (35%) compared to clinic TBP were younger, had higher self-reported skin cancer risk, and were more likely to have had previous TBP sessions. Overall, the number of TBP sessions increased, while dermoscopy usage and biopsy number decreased. There was no change in the number and distribution of skin cancer diagnoses compared to the same period in 2019. The Melanoma-In-Situ:Invasive Melanoma (MIS:INV) ratio was above the U.S. ratio reported for 2020 of 0.95:1 (95,710 MIS:100,350 INV). Semi-automated TBP was successfully implemented during the pandemic without affecting skin cancer detection.

Risk Factors for Malignant Melanoma in Romania

In all ages of population in the recent decades, Malignant melanoma is the most dangerous type of skin cancer in the whole world. Its incidence has increased worldwide and that for and earlier diagnosis programs, who reduce the morbidity and mortality of the malignant disease . The Parisian physician Rene Laennac’s was the first who reported 200 years ago, the presence of melanoma in Europe

Diagnosis of Melanoma Based on the Sparse Auto-Encoder for Feature Extraction

Aims: Skin cancer is a fairly critical disease all over the world and especially in Western countries and America. However, if it is perceived and treated early, it is quite often curable. The main risk factors for melanoma are exposure to UV rays, the presence of many moles, and heredity. For this reason, this work focuses on the issue of automatic diagnosis of melanoma. The aim is to extract significant features from pixels of the images based on an unsupervised deep learning technique which is the sparse autoencoder method.&#x0D; Methodology: A preprocessing phase is required to remove the artifacts and enhance the contrast of the images before proceeding with the feature extraction. Once the characteristics are extracted automatically, the support vector machine classifier and the k-nearest neighbors are applied for the classification phase. The objective is to differentiate between 3 categories: melanoma, suspected case, and non-melanoma. Finally, the PH2 database is used to test the proposed approaches (200 images are presented in this dataset: 80 atypical nevi, 80 common nevi, and 40 melanoma).&#x0D; Results: The obtained results in terms of specificity, accuracy, and sensitivity present noticeable performances with the support vector machine classifier (achieved 94 % overall accuracy) and the k-nearest neighbors (92 %).&#x0D; Conclusion: This study's experimental findings showed that the best performance was obtained by the approach based on a deep sparse autoencoder combined with support vector machine.

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

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Associations between ultraviolet radiation, tree cover and adolescent sunburns

BackgroundSunburn is the strongest risk factor for melanoma and non-melanoma skin cancers. Adolescent sunburns are related to higher risk of developing melanoma later in life. Little is known about the association of sunburns and shade, particularly tree cover, around adolescent homes and schools. This linkage study assessed associations of adolescent self-reported sunburns with ambient ultraviolet radiation (UV) and tree cover.MethodsWe analyzed a U.S. national sample of parent–child dyads (n = 1333) from the 2014 Family Life, Activity, Sun, Health, and Eating (FLASHE) study conducted by the National Cancer Institute. The outcome was adolescent sunburns reported for the previous 12 months. GIS buffers around geocoded home and school addresses were used to summarize UV and tree cover. A sensitivity analysis assessed different UV measures and tree cover buffer distances. Logistic regression models estimated the adjusted odds of any sunburns for five models: (1) no environmental variables; (2) spatial variables of latitude and longitude; (3) UV; (4) tree cover; and, (5) a combined model with UV and tree cover. Covariates included common sunburn-related items such as sun protective behaviors, socio-demographics, and latitude. Model residuals were assessed for spatial dependency and clustering.ResultsOverall, 44% of adolescents reported any sunburns in the previous 12 months. For the bivariate associations, lower categories of UV were associated with any reported sunburns (p-trend = 0.002). Home tree cover was not associated with any reported sunburns (p-trend = 0.08), whereas schools with lower categories of tree cover were associated with sunburns (p-trend = 0.008). The adjusted odds of any sunburns by UV tertiles, as a linear tread, was 0.89 (0.76–1.05) (p = 0.17); school tree cover was: 0.91 (0.78–1.07) (p = 0.25). Neither UV nor tree cover, in a combined model, were significant. Sensitivity analyses resulted in the optimal buffer size of 200 m for summarizing tree cover. Spatial dependence of residuals was not significant and clustering was significant for about 6% or less of the sample in each model.ConclusionsWe did not find significant relationships between UV or tree cover and adolescent sunburns, when adjusted by sunburn-related covariates. Better contextual data about where sunburns occurred is needed to identify environmental correlates of sunburn.

Eruptive Cherry Angiomas and Skin Melanoma: Further Insights into an Intriguing Association

Background: Some risk factors for malignant melanoma (MM) are recognized. Objective: To compare the strength of association between MM and eruptive cherry angiomas (CAs) with that of other well-known associations. Methods: This cross-sectional study included all subjects referred to the Outpatient Dermatology-Oncology and Dermoscopy Units of the Universities of Ferrara and Bologna, Italy, over a 5-month period and submitted to total body skin examination. We recorded: age, sex, cutaneous and non-cutaneous malignancies, presence of CAs, arbitrarily considered as “eruptive” when >10, >40 common melanocytic naevi or >2 clinically atypical naevi. The strength of association between the possible risk factors and MM was calculated by odds ratio in both the whole population and age quartiles. Variables associated with MM were included in multiple logistic regression analysis. Results: 1,190 subjects were included; 615 had malignant skin tumours, 462 MM, 85 extracutaneous tumours. Five hundred and eighty-seven subjects had eruptive CAs, 485 subjects >40 melanocytic naevi and 368 more than 2 atypical melanocytic naevi. Eruptive CAs, especially in subjects younger than 70, and >2 atypical melanocytic naevi, mostly in subjects older than 50, were significantly associated with MM. The strength of these 2 associations was similar. The presence of >40 melanocytic naevi was not associated with MM. Conclusions: These findings confirmed an association between MM and eruptive CAs, which was as strong as the one between MM and >2 atypical melanocytic naevi. CAs seem an intriguing model of interaction between heterogeneous variables, like immunocompetence, stimuli inducing endothelial cell proliferation, and oncogenesis, which deserves further investigation.

15947 Inaccuracy of self-reported family history of melanoma in high-risk patients

Family history of melanoma is a known major risk factor for melanoma. However, self-reported family histories for numerous cancers, including melanoma, are commonly inaccurate. Three large melanoma studies have explored this with positive predictive values (PPVs), 28%-83%. Given these wide variations, we explored this question in individuals at high-risk of melanoma, and thus, more likely to be aware of their family history of melanoma. We queried the Utah Population Database (UPDB), a unique, extensive family history database linking >11,000,000 individuals with public records (driver’s license, marriage/divorce records), medical records and death records. This offers a more complete multi-generational dataset for a much larger cohort than would be feasible through manual chart review and is the largest cohort study to date. Charts from 1780 high-risk patients (having at least one melanoma risk factor) were reviewed to quantify self-reported family history of melanoma. These data were combined with UPDB and Utah Cancer Registry data serving as the “gold standard.” Self-reported family history of melanoma in first- and second-degree relatives had an overall sensitivity of 62%, specificity of 67%, PPV of 31%, and NPV of 89%, with increased accuracy for first-degree relatives. A personal history of melanoma was the only factor associated with increased accuracy in self-reported family history of melanoma. Age, sex, number of nevi, and number of prior personal melanomas were not significant. Dermatologists should educate patients on the differences between melanoma, nonmelanoma skin cancer and pre-cancers. Confirming self-reported family history of melanoma will limit over-screening of otherwise low-risk patients.

15665 UV exposure and the risk of cutaneous melanoma in skin of color

Background: Although the evidence for UV exposure as a risk factor of cutaneous melanoma has been established in light skinned populations, the evidence for the relationship in people with skin of color is less certain.