Risk Of Melanoma Skin Cancer Research Articles

A two-step, two-sample Mendelian randomization analysis investigating the interplay between gut microbiota, immune cells, and melanoma skin cancer.

This study aims to rigorously explore the potential causal relationships among gut microbiota (GM), immune cells, and melanoma skin cancer among participants from Europe, where this disease exhibits significant prevalence and profound societal impact. Using the genome-wide association analysis database, a double-sample Mendelian randomization (MR) analysis was drawn upon to investigate GM, immune cells, and melanoma skin cancer. The inverse variance weighted approach was applied to estimate the causal connections among these variables. A two-step MR analysis was employed to quantitatively gauge the impact of immune cells mediated GM on melanoma skin cancer. To address potential sources of bias, such as pleiotropy and heterogeneity, multiple analytical techniques were integrated. The MR analysis pinpointed 6 GM taxa related to either an augmented or declined risk of late-stage melanoma skin cancer. In the same vein, 32 immune cell phenotypes were noticed as correlates with modified risk of melanoma skin cancer. Our study also implies that the probable association between GM and melanoma could be facilitated by 5 immune cell phenotypes. The findings of our study underline certain GM taxa and immune cells as potential influencers on the onset and development of melanoma skin cancer. Importantly, our results spotlight 5 immune cell phenotypes as potential agents mediating this association.

Hormone replacement therapy and the risk of melanoma in post-menopausal women.

Is hormone replacement therapy (HRT) associated with an increased risk of melanoma skin cancer or prognostic outcomes amongst post-menopausal women? Whilst we found evidence of an association with melanoma risk, the lack of dose-response and associations observed with recent use, localised disease and intravaginal oestrogens suggests this is a non-causal association. Evidence on HRT and melanoma risk remains inconclusive, with studies providing conflicting results. Furthermore, evidence on melanoma survival is sparse, with only one previous study reporting protective associations with HRT use, likely attributable to immortal time bias. We conducted a nation-wide population-based case-control study and a retrospective cohort study utilising the Danish healthcare registries. Case-control analyses included 8279 women aged 45-85 with a first-ever diagnosis of malignant melanoma between 2000 and 2015, matched by age and calendar time to 165 580 population controls. A cohort of 6575 patients with a diagnosis of primary malignant melanoma between 2000 and 2013 and followed through 2015 was examined to determine if HRT use had an impact on melanoma survival outcomes. Based on prescriptions dispensed since 1995, ever-use of HRT was defined as having filled at least one prescription for HRT prior to the index date. In total, 2629 cases (31.8%) and 47 026 controls (28.4%) used HRT. Conditional logistic regression was used to calculate odds ratios (ORs) for melanoma risk according to HRT use, compared with non-use, adjusting for potential confounders. For cohort analyses, Cox proportional hazards models was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for second melanoma incidence and all-cause mortality associated with HRT. High use of HRT was associated with an OR of 1.21 (95% CI 1.13-1.29) for melanoma risk, with no evidence of a dose-response pattern. Results were most pronounced amongst recent high users (OR, 1.28; 95% CI 1.17-1.41), for localised disease (OR, 1.25; 95% CI 1.15-1.36) and for intravaginal oestrogen therapy (OR, 1.38; 95% CI 1.13-1.68). Compared with non-use, there was no evidence of an association for secondary melanoma for post-diagnostic new-use (fully adjusted HR, 1.56; 95% CI 0.64-3.80) or continuous HRT use (fully adjusted HR, 1.26; 95% CI 0.89-1.78). Similar associations were observed for all-cause mortality. Despite the large sample size and the use of robust population-based registries with almost complete coverage, we lacked information on some important confounders including sun exposure. Whilst we cannot rule out an association between HRT use and melanoma risk, the associations observed are also compatible with increased healthcare utilisation and thus increased melanoma detection amongst HRT users. No association between HRT use and melanoma survival outcomes was observed. This should provide some reassurance to patients and clinicians, particularly concerning the use of HRT in patients with a history of melanoma. B.M.H. is funded by a Cancer Research UK Population Research Postdoctoral Fellowship. The funding source had no influence on the design or conduct of this study. A.P. reports participation in research projects funded by Alcon, Almirall, Astellas, Astra-Zeneca, Boehringer-Ingelheim, Servier, Novo Nordisk and LEO Pharma, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this article. The other authors have no competing interests to declare. N/A.

Lack of association of metastasis-associated lung adenocarcinoma transcript 1 variants with melanoma skin cancer risk.

The long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in melanoma. Polymorphisms in MALAT1 may play a vital role in the progress of melanoma by its regulative function. However, potential genetic variants in MALAT1 affecting the risk of melanoma onset have not been explored. In this study, two single nucleotide polymorphisms (rs3200401 and rs619586) in MALAT1 were selected for genotyping of 334 melanoma patients and 291 cancer-free controls in an Italian population. The results showed that MALAT1 rs3200401 and rs619586 were not associated with melanoma risk. A further breakdown analysis by sex stratification also indicated a lack of association between these polymorphisms and melanoma. In addition, we tested 450 bp of the proximal 5´ flanking region of the gene for the presence of polymorphisms that could be associated with melanoma risk and found no variants in 96 melanoma patients. In conclusion, our results suggest that there is no contribution of MALAT1 rs3200401 and rs619586 polymorphisms or polymorphisms in the core promoter that could be associated with the risk of melanoma skin cancer in this specific study setting. Further validation will be required in larger studies involving different settings/larger populations in order to reach conclusive results.

Melanoma risk modeling from limited positive samples

The key to effective cancer treatment is early detection. Risk models built from routinely collected clinical data have the opportunity to improve early detection by identifying high-risk patients. In this study, we explored various machine learning techniques for building a melanoma skin cancer risk model. The dataset contains records of routine dermatology office visits from 9,531,408 patients spread throughout the United States. Of these patients, 17,246 (0.18%) developed melanoma. We conducted extensive experiments to effectively learn from this dataset with limited positive samples. We derived datasets with more severe class imbalance and tested several classifiers with different data sampling techniques to build the best possible model. Additionally, we explored various properties of the datasets to determine relationships between class distributions and model performance. We found that randomly removing negative cases from the training datasets significantly improved model performance. K-means clustering of different groups of instances shows that there is greater homogeneity in negative samples, and the model results reflect that removing these samples increases overall model performance. This experiment provides a reference framework for future risk models, since most datasets will have a plethora of healthy patients, but only a few key patients that are at high risk for developing a disease.

Follow-up study of skin cancer in a U.K. paediatric transplant population

It is well-known that adults who undergo liver or kidney transplantation are more likely to develop skin cancer. This is because medicines given to prevent rejection of the transplanted organ also lower the body's resistance to cancer. Less is known about the skin cancer risk in children who have undergone organ transplantation (paediatric organ transplant recipients, POTRs). In this study, researchers in Birmingham, U.K. examined 45 patients for skin cancer following liver or kidney transplantation in childhood. The same patients had been examined 10 years earlier, when no skin cancers were found. Their average age was now 24 years, and time since transplantation ranged from 15 to 26 years. Ethnically, 34 were white, while 7 had racially pigmented skin. Again, there were no skin cancers or suspicious lesions, but 41 of the 45 had significantly more moles than 10 years earlier, 71% in sun-exposed sites, particularly arms. Eleven had more than 50 moles, an excessively high number indicating an increased risk of melanoma skin cancer. Despite previous advice about sun-protection because of the skin cancer risk, 78% had experienced sunburn, particularly those who took holidays abroad, and 22% admitted using sunbeds. Those who had been sunburnt more often had more moles on the legs and back. Curiously those with more moles on the arms had used more sunscreen, but perhaps not enough for their amount of sun exposure. The lack of skin cancer in these POTRs at 15-26 years post-transplant is encouraging and compares well with other studies showing first cancers in POTRs at 12-19 years. However, it is no cause for complacency: these young people remain at risk and clearly need better, age-appropriate education about sun-protection.

Inflammatory Bowel Disease and Skin Cancer: Adherence to Quality Measures

Introduction: Previous literature has reported poor documentation related to quality metrics in inflammatory bowel disease (IBD) patients, one of which is skin cancer surveillance. The increased risk for melanoma skin cancer (MSC) in IBD patients has been discussed in the literature prior to biologic therapies becoming available. A recent retrospective cohort study suggested that the use of anti-TNF agents increases the risk of developing MSC. A recent meta-analysis demonstrated a statistically significant 37% increased risk of developing MSC in IBD patients when compared to the general population. In addition, there is a known increased risk of non-MSC in IBD patients who have received thiopurines. In view of this, the American College of Gastroenterology (ACG) has released new clinical guidelines recommending skin cancer screening in IBD patients regardless of the use of biologic therapy. Methods: In an IRB-approved chart review we identified all patients aged 18+ seen at our hospital system between 1/2010 and 12/2015 with ICD-9 diagnosis code for UC (556.xx) or CD (555.xx). An abstraction was used to document clinical history and health maintenance metrics, including skin cancer screening. Characteristics were compared between those with and without skin cancer screening documentation using Chi-square and Wilcoxon Rank-Sum tests. 2-sided p-values of < 0.05 were considered statistically significant. Results: 184 patients were eligible for review (Table 1). The median age 44.5 (IQR 31.6, 58.8), 45% male, 81% white non-Hispanic. The most common diagnostic subtypes were CD penetrating (n=43, 32%), CD inflammatory (n=36, 26.9%) and UC pancolitis (n=29, 22%). About half of the patients (n=100, 54%) were either on a biologic (n=65, 35%) or immunomodulator agent (n=81, 44%). Of these, only 4 (4.0%, 95% CI 1.5%, 10.3%) had documented skin cancer screening (Table 2). Screened patients were older (median 63 years vs. 42 years, p=0.12, Wilcoxon rank-sum), and were more likely to be White (3/4 or 75%) versus Black/AA patients (0/4 or 0.0%) or Hispanic (0/4 or 0.0%) (p < 0.001).Table: Table. Characteristics of Patients in the Study (n=184)Table: Table. Characteristics of Patients on Immunomodulators/Biologics Screened for Skin Cancer vs. NotConclusion: We have conclusive data to support the association between IBD and its pharmacotherapies with an increased risks of skin cancer. It is critical to recognize IBD patients as high risk individuals for developing skin malignancies. Our data is in line with the national trend of poor adherence to skin cancer screening in IBD patients. Adherence to the ACG preventative care guidelines is of supreme importance.

Phosphodiesterase Type 5 Inhibitors and the Risk of Melanoma Skin Cancer

BackgroundThe association between phosphodiesterase type 5 inhibitors (PDE5-Is), drugs used in the treatment of erectile dysfunction (ED), and melanoma skin cancer is controversial. ObjectiveTo assess whether the use of PDE5-Is is associated with an increased risk of melanoma skin cancer. Design, setting, and participantsUsing the UK Clinical Practice Research Datalink, we assembled a cohort of men newly diagnosed with ED between 1998 and 2014 and followed until 2015. PDE5-I exposure was considered as a time-varying variable lagged by 1 yr for latency purposes. Outcome measurements and statistical analysisCox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident melanoma associated with PDE5-I use overall and by number of prescriptions and pills received. Identical analyses were conducted for basal and squamous cell carcinoma, two cancers for which PDE5-related pathways are not thought to be involved. Results and limitationsThe cohort included 142 983 patients, of whom 440 were newly diagnosed with melanoma during follow-up (rate: 63.0 per 100 000 person-years). Compared with nonuse, PDE5-I use was not associated with an overall increased risk of melanoma (rates: 66.7 vs 54.1 per 100 000 person-years; HR: 1.18; 95% CI, 0.95–1.47). The risk was significantly increased among those who had received seven or more prescriptions and ≥25 pills (HR: 1.30 [95% CI, 1.01–1.69] and 1.34 [95% CI, 1.04–1.72], respectively). In contrast, there was no overall association with basal and squamous cell carcinoma, with an unclear association with numbers of prescriptions and pills received. ConclusionsThe use of PDE5-Is was not associated with an overall increased risk of melanoma skin cancer. The increased risks observed in the highest prescription and pill categories require further validation. Patient summaryIn this study, the use of phosphodiesterase type 5 inhibitors was not associated with an increased risk of melanoma skin cancer.

The Epidemiology of Vitiligo

Vitiligo is a common condition seen in a dermatology office, which has a variety of comorbidities. Worldwide, the prevalence of vitiligo ranges from 0.4 to 2.0 %, with regions of greater or lesser prevalence. Most studies demonstrate slightly greater prevalence in females and 50 % onset in childhood, but exceptions to these rules exist. Childhood vitiligo has been associated with atopic diathesis, halo nevi, and family history of vitiligo and autoimmunity. Post-pubescent vitiligo has been associated with greater acrofacial disease and thyroid disease, and early data supports reduced non-melanoma and melanoma skin cancer risk. Disease severity is inversely proportional to distance from the equator, and birthplace outside the USA may be somewhat protective against severe disease. This article reviews the epidemiology of vitiligo and the epidemiologic relationship of vitiligo to comorbid diseases and family history, with a focus on recent literature.

Melanoma and non-melanoma skin cancer in inflammatory bowel disease patients following tumor necrosis factor-α inhibitor monotherapy and in combination with thiopurines: analysis of the Food and Drug Administration Adverse Event Reporting System.

Reports have shown an increased risk of melanoma skin cancer (MSC) with exposure to tumor necrosis factor alpha (TNF-α) inhibitors and non-melanoma skin cancer (NMSC) with thiopurine exposure in inflammatory bowel disease (IBD) patients. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) we sought to evaluate the odds of developing MSC and NMSC for patients on TNF-α inhibitors as monotherapy and in combination therapy with thiopurines and/or steroids. The FAERS was queried for reports between January 2003 and June 2012. A proportional reporting ratio (PRR) metric analyses was performed on the data to determine the odds of developing MSC and NMSC. The PRR analysis showed increased odds of developing MSC and NMSC for patients on a TNF-α inhibitor (p-value = 0.035 and p-value = 0.03, respectively) and those on a TNF-α inhibitor in combination with a thiopurine (p-value < 0.001 and p-value < 0.001). TNF-α inhibitor monotherapy or use with concomitant thiopurines in patients with IBD is associated with higher odds of developing MSC and NMSC.

Impact of Ultraviolet Photography on Sun Safety Practices of Snow Sport Industry Conference Attendees

Studies have established ultraviolet (UV) exposure with increased melanoma skin cancer risk. The combination of UV exposure, high altitude, and reflection of UV rays on the snow may create a particularly relevant and high-risk population amongst those who participate in snow sports. The current study aims to determine the effectiveness of a UV-photography and personalized counseling-based intervention to improve sun protection awareness on the snow sport enthusiast population. Participants were recruited at the 2013 SnowSports Industries American (SIA) Snow Show in Denver to complete a 14 question pre-survey assessing sun-safety awareness followed by a Faraghan Medical Elise Digital UV Camera photograph of their face and counseling regarding individual results. Participants were contacted one to two months later by telephone to complete a ten question post-survey. Forty-one percent of participants (46/112) completed both pre- and post-surveys. The UV photography based intervention influenced the opinions and behaviors of sun protection in 78% of male and 62% of female participants with sunscreen use identified as the most frequently modified behavior (53%). While valid barriers to UV photography use include a current lack of reimbursement and lack of public knowledge of its utility, our study indicates the potential impact of UV photography-based interventions among high-risk populations who avidly participate in snow sports.

Risk-adjusted melanoma skin cancer incidence rates in Whites (United States)

The objective of this study was to obtain a better population-based measure of risk for melanoma skin cancer. A method has been previously proposed for estimating cancer incidence rates for data collected from the Surveillance, Epidemiology, and End Results (SEER) program. Unlike conventionally reported incidence rates in the USA, this method uses the first primary cancer and adjusts for population-based cancer prevalence to obtain a better measure of cancer risk. The study involves SEER data for white men and women. Conventional melanoma incidence rates overestimate risk for men, increasingly so from 3.3% in the age group of 30-39 years to 11.3% in the age group of 80 years and older. Overestimation in risk for women ranged from 3.3% in the age group of 30-39 years to 8.9% in the age group of 80 years and older. Overestimation of risk was more pronounced when both in-situ and malignant melanomas were considered. Increasing trends in conventional rates were slightly greater than trends in risk-adjusted incidence rates (RAIRs). In 2007, the estimated number of cases with malignant melanoma among the white population based on conventional cancer incidence rates is 37 636 (64 125 including in-situ cases) for men and 28 935 (49 361 including in-situ cases) for women. The estimated number of cases in the USA based on RAIRS is 34 652 [(7.9%); 55 413 (13.6%) including in-situ cases] for male and 27 178 [(6.1%); 44 467 (9.9%) including in-situ cases] for women. We concluded that RAIRs are a better measure of melanoma skin cancer risk and should be used for estimating the number of cancer patients in the USA.

Patient adherence to skin self-examination: effect of nurse intervention with photographs

Background Results from a single case–control study suggest that skin self-examination (SSE) has the potential to reduce mortality from melanoma by 63%. Despite these encouraging results, SSE rates are low. Few prospective studies of interventions to increase SSE in high-risk cohorts have been performed. The purpose of this study was to assess the impact of a brief nurse-delivered intervention using digital photographs on patients' adherence to performing SSE. Design setting/participants Patients at high risk for melanoma skin cancer (five or more dysplastic nevi) (N=100) were recruited from the outpatient Pigmented Lesion Clinic at Memorial Sloan–Kettering Cancer Center. All participants had baseline whole-body digital photography as part of their clinical evaluation. Intervention Patients were randomized: Group A ( n =49) received a teaching intervention (physician and nurse education module) with a photo book (personal whole-body photographs compiled in the form of a booklet, with nurse instruction on how to use the photographs); and Group B ( n =51) received the teaching intervention only without a photo book. Main outcome/measures Self-administered questionnaires were provided at three intervals: baseline, post-teaching intervention, and at the 4-month post-baseline visit. To assess adherence with SSE, patients were asked, “How many times in the past 4 months did you (or someone else) usually, thoroughly examine your skin?” Results In Group A (teaching intervention with photo book), 10.2% of the patients at baseline reported skin examination three or more times during the past 4 months, while 61.2% reported skin examination three or more times at the 4-month follow-up ( p =0.039 for paired comparison). In Group B (teaching intervention only), nearly 20% of the patients at baseline reported skin examination three or more times during the past 4 months, while 37% reported skin examination three or more times at the 4-month follow-up ( p =0.63). The increase in reported skin examination was compared between the two groups (>51% v >17.6%, p =0.001). Conclusions The results suggest that a brief nurse-delivered intervention is effective at increasing patient adherence with SSE. Utilizing digital photographs as an adjunct to screening appeared to increase patient adherence to performing SSE.

Sunscreen use, wearing clothes, and number of nevi in 6- to 7-year-old European children. European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

Previous epidemiologic studies have suggested that sunscreen use is associated with an increased risk of melanoma skin cancer. Because high nevi (mole) count in adults is a strong predictor of melanoma, we conducted a study examining the number of nevi in 6- to 7-year-old European children, according to their sunscreen use. Whole-body and site-specific counts of nevi 2 mm or larger were performed in 631 children in their first year of primary school in four European cities. Independently, parents were interviewed regarding sun exposure, sunscreen use, and physical sun protection of their child. After adjustment for sun exposure and host characteristics (e.g., skin phototype, eye color), the relative risk for high nevus count on the trunk was 1.68 (95% confidence interval [CI] = 1.09-2.59) for the highest level of sunscreen use and 0.59 (95% CI = 0.36-0.97) for the highest level of wearing of clothes while in the sun. The sun protection factor had no effect on nevus counts despite a high median value of 17.4. Sunburn number was not associated with nevus count. The highest risk associated with sunscreen use was found among children who had never experienced sunburn. In white, European children, sunscreen use appears to be associated with development of nevi, probably because it allows longer sun exposures. Wearing clothes may be an effective way to prevent proliferation of nevi. Since a high nevus count is a strong predictor of melanoma, sunscreen use may be involved in melanoma occurrence because it may encourage recreational sun exposure.

Mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States.

That sunlight leads to skin cancer has been generally accepted for nearly a century. Physical data are, for the first time, available which support this hypothesis. The authors have found that a simple power relationship can be used to describe the data and that the form of this power function suggests that the risk of nonmelanoma skin cancer is related to cumulative lifetime ultraviolet (UV) exposure and that the risk of melanoma skin cancer is related to annual UV exposure. The authors emphasize that skin cancer risk also depends on location-specific demographic variables other than ultraviolet radiation.