Increased Risk Of Skin Cancer Research Articles

Alternative autophagy dampens UVB-induced NLRP3 inflammasome activation in human keratinocytes

Sunlight exposure results in an inflammatory reaction of the skin commonly known as sunburn, which increases skin cancer risk. In particular, the ultraviolet B (UVB) component of sunlight induces inflammasome activation in keratinocytes to instigate the cutaneous inflammatory responses. Here, we explore the intracellular machinery that maintains skin homeostasis by suppressing UVB-induced inflammasome activation in human keratinocytes. We found that pharmacological inhibition of autophagy promoted UVB-induced NLRP3 inflammasome activation. Unexpectedly, however, gene silencing of Atg5 or Atg7, which are critical for conventional autophagy, had no effect, whereas gene silencing of Beclin1, which is essential not only for conventional autophagy but also for Atg5/Atg7-independent alternative autophagy, promoted UVB-induced inflammasome activation, indicating an involvement of alternative autophagy. We found that damaged mitochondria were highly accumulated in UVB-irradiated keratinocytes when alternative autophagy was inhibited, and they appear to be recognized by NLRP3. Overall, our findings indicate that alternative autophagy, rather than conventional autophagy, suppresses UVB-induced NLRP3 inflammasome activation through the clearance of damaged mitochondria in human keratinocytes, and illustrate a previously unknown involvement of alternative autophagy in inflammation. Alternative autophagy may be a new therapeutic target for sunburn and associated cutaneous disorders.

Skin Cancer Risk Is Increased by Somatic Mutations Detected Noninvasively in Healthy-Appearing Sun-Exposed Skin

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Since UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. Herein, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1,038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk, DNA-SCAR) was trained to predict personal history of skin cancer from age, family history, skin tone and mutation count. The addition of mutation count significantly improved model performance (OR=1.3 95%CI:1.14-1.48; p-value=5.3x10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known U.S. population prevalence, indicating DNA-SCAR was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection via adhesive patches.

Group I pharmaceuticals of IARC and associated cancer risks: systematic review and meta-analysis

We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran’s Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07–1.62; SRR = 1.56, 95% CI 1.25–1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32–6.23; SRR = 2.43, 95% CI 1.65–3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49–18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30–15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.

Incidence and profile of skin cancers in patients following ultraviolet phototherapy without psoralens: A retrospective cohort study

Psoralen+ultraviolet-A (PUVA) is associated with photocarcinogenesis. However, carcinogenic risk with other ultraviolet phototherapies remains unclear. Evaluate whether phototherapy without psoralens increases skin cancer risk. Retrospective cohort study of patients treated at a teaching-hospital phototherapy center (1977-2018). Skin cancer records were validated against pathology reports. Age-standardized incidence rates (ASIRs) of skin cancer were evaluated for gender, skin phototype, diagnosis, ultraviolet modality, anatomical site; and compared to provincial population incidence rates (2003). In total, 3506 patients treated with broadband-ultraviolet-B, narrowband-UVB and/or combined UVAB were assessed with a mean follow-up of 7.3years. Majority of patients had psoriasis (60.9%) or eczema (26.4%). Median number of treatments was 43 (1-3598). Overall, 170 skin cancers (17 melanoma, 33 squamous cell carcinoma and 120 basal cell carcinoma) occurred in 79 patients. Patient-based and tumor-based ASIR of skin cancer was 149 (95% CI: 112-187)/100,000 and 264 (219-309)/100,000 person-years, respectively. There was no significant difference between tumor-based ASIRs for melanoma, squamous cell carcinoma, and basal cell carcinoma compared to the general population; or in phototherapy patients with-psoriasis or eczema; or immunosuppressants. No cumulative dose-response correlation between UVB and skin cancer was seen. Treatment and follow-up duration. No increased risk of melanoma and keratinocyte cancer was found with phototherapy.

Methotrexate did not add skin cancer risk in patients with psoriasis receiving narrowband ultraviolet B phototherapy: a nationwide retrospective cohort study.

In the era of biologic therapy, phototherapy and methotrexate (MTX) are still commonly used for treatment in patients with moderate-to-severe psoriasis. However, the skin cancer risk following a combination of MTX and narrowband ultraviolet B (NB-UVB) has rarely been explored. To investigate whether MTX plus NB-UVB increases skin cancer risk in patients with psoriasis. We conducted a retrospective cohort study of data in the Taiwan National Health Insurance Research Database from 1997 to 2013. Cumulative incidences and multivariate analysis were investigated using a competing risk regression model, comparing skin cancer risk between cohorts of people having combination therapy and those using NB-UVB alone, matched for relative confounders. We further conducted a sensitivity analysis for those receiving a higher MTX dose. Standardized incidence ratios (SIRs) were calculated for skin cancer risk. We enrolled 3203 participants in each cohort. No significant differences in skin cancers were noted between the two cohorts for the cumulative incidences (log-rank test, P = 0.28) and for the hazard ratio (HRs) [adjusted HR 0.50, 95% confidence interval (CI) 0.15-1.63, P = 0.247] in the competing risk regression model. There were also no significant differences between those receiving higher-dose MTX and UVB alone in the cumulative incidences of skin cancers (P = 0.23) and the HR (adjusted HR = 0.29, 95% CI 0.04-2.21, P = 0.23) in the multivariate analysis. There was no significant difference in the SIR between the two cohorts compared with the general population. In the Taiwanese population, MTX does not increase skin cancer risk in patients with moderate-to-severe psoriasis receiving NB-UVB.

Do Indoor LED Grow Lights Emit Sufficient UV Irradiation to Pose an Increased Skin Cancer Risk?

Do Indoor LED Grow Lights Emit Sufficient UV Irradiation to Pose an Increased Skin Cancer Risk?

What is the relationship between photosensitizing drugs and skin cancer?

Many medications are associated with phototoxicity or photoallergy, the two types of photosensitivity. Recently, a warning related to increased skin cancer risk was added to the labeling of the popular diuretic hydrochlorothiazide. This article reviews some photosensitizing medications and describes patient education on preventing and recognizing photosensitivity reactions and skin cancer.

Genomic mutation landscape of skin cancers from DNA repair-deficient xeroderma pigmentosum patients

Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis DNA polymerase η (V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyze 38 skin cancer genomes from five XP groups. We find that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors and experiments with POLH knockout cell line reveal the role of polymerase η in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3’ nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.

Risk of Melanoma and Nonmelanoma Skin Cancer in People with Vitiligo: United Kingdom Population−Based Cohort Study

Although genetic studies have found an inverse relationship between vitiligo and skin cancer, epidemiological evidence is conflicting. We investigated the risk of skin cancer in adults with vitiligo using United Kingdom electronic primary care records from the Optimum Patient Care Research Database 2010-2020. Vitiligo cases were age, sex, and general practitioner practice matched to population controls without vitiligo. Incidence of melanoma, nonmelanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), and actinic keratoses was compared between vitiligo cases and controls using Cox regression. A total of 15,156 vitiligo cases were matched to 60,615 controls. Vitiligo was associated with a 38% reduced risk of new-onset skin cancer (adjusted hazard ratio [aHR]= 0.62, 95% confidence interval [CI]= 0.52-0.75, P < 0.001) and skin cancer subtypes; melanoma (aHR= 0.39, 95% CI= 0.23-0.65, P < 0.001), squamous cell carcinoma (aHR= 0.67, 95% CI= 0.49-0.90, P < 0.01), basal cell carcinoma (aHR= 0.65, 95% CI= 0.51-0.83, P < 0.001). There was no significant association for actinic keratosis (aHR= 0.88, 95% CI= 0.77-1.01). People with vitiligo have a markedly reduced incidence of melanoma and nonmelanoma skin cancer. Given concerns that some treatments, such as phototherapy, may increase skin cancer risk, this finding provides reassurance to people with vitiligo and clinicians managing the condition.

Chronic Use of Hydrochlorothiazide and Risk of Skin Cancer in Caucasian Adults: A PharmLines Initiative Inception Cohort Study.

Photosensitizing properties of hydrochlorothiazide may increase skin cancer risk. To date, study findings on the association between hydrochlorothiazide use and skin cancer risk are inconsistent, notably regarding confounding and dose-response. The aim of this study was to investigate the association between hydrochlorothiazide use and incidence of skin cancer in a cohort of unselected Caucasian adults, taking dosing into account. As part of the PharmLines Initiative, which links data from the Lifelines Cohort Study and prescription database IADB.nl, patients aged ≥ 40 years were included from Lifelines, a prospective population-based cohort study in the north of the Netherlands. Skin cancer incidence was compared between subjects starting hydrochlorothiazide treatment (n = 608), subjects starting treatment with other antihypertensives (n = 508), and non-antihypertensive long-term medication users (n = 1,710). Cox regression analyses were performed to obtain hazard ratios, adjusted for potential confounders. The risk of any skin cancer, keratinocyte carcinoma, basal cell carcinoma and squamous cell carcinoma was not significantly increased in general hydrochlorothiazide users. A clear association was observed between high cumulative hydrochlorothiazide use (≥ 5,000 defined daily dose; ≥ 125,000 mg) and the risk of any skin cancer (adjusted hazard ratio 5.32, 95% confidence interval (95% CI) 2.40-11.81), keratinocyte carcinoma (adjusted hazard ratio 7.31, 95% CI 3.12-17.13), basal cell carcinoma (adjusted hazard ratio 7.72, 95% CI 3.11-19.16) and squamous cell carcinoma (adjusted hazard ratio 19.63, 95% CI 3.12-123.56). These findings should lead to awareness with high use of hydrochlorothiazide in Caucasian adults.

Association of hydrochlorothiazide treatment compared with alternative diuretics with overall and skin cancer risk: a propensity-matched cohort study.

Hydrochlorothiazide (HCT) has been suggested to induce photosensitivity, thereby increasing the incidence of skin cancers. After a pharmacovigilance alert, HCT was frequently withdrawn or substituted by other diuretics. The aim of this study was to compare the association of exposure to HCT with cancer risk versus alternative diuretics. A retrospective cohort study was conducted based on data from the AOK PLUS, a large German statutory health insurance fund. Patients with HCT treatment were propensity score matching to patients using non-HCT diuretics. Incidence of cancer of any kind and, specifically, skin cancer was assessed in both groups. Time-to-incident cancer diagnosis was evaluated and compared between the groups. A total of 199 708 patients were included in the final analysis ( n = 76 855 in the HCT group; n = 122 853 in the non-HCT-diuretics group). After propensity score matching, 122 554 patients remained in the sample ( n = 61 277 for both groups, of which >96% had hypertension, mean age 73 years, 61% female). HCT treatment was associated with a lower incidence of cancer of any kind compared with non-HCT diuretics (incidence rate ratio per 100 patient years 0.84 95% confidence interval: 0.82-0.87). HCT treatment was associated with a small albeit significantly higher incidence rate ratio of skin cancer (1.15 95% confidence interval: 1.06-1.24) with significant variances over time. Although numerically higher, the difference accounts to only 0.05 more skin cancer diagnoses in 100 patient-years. HCT treatment compared with alternative diuretics was associated with a lower all-cancer risk and a numerically small increased skin cancer risk in a large German population. Risk-benefit evaluation should be executed in patients with increased skin cancer risk and treatment with HCT. Furthermore, advice for skin protection is warranted in all patients taking thiazide or thiazide-like diuretics.

Risk of skin cancer in kidney, liver and heart recipients: A nationwide population-based study in Taiwan.

Background Previous population-based studies in western countries had revealed increased skin cancer risk among transplant recipients compared to the general population. However, population-based studies in Asia on skin cancer among recipients of different transplanted organs were lacking in the literature. Aims This study aims to estimate skin cancer risk among recipients in Taiwan, examine the association between each specific type of skin cancer and each type of transplanted organ, and compare skin cancer risk between different immunosuppressive regimens. Methods This population-based retrospective cohort study identified 7550 patients with heart, lung, kidney or liver transplantation and 30,200 controls matched for gender, age and comorbidity index from the National Health Insurance Research Database in Taiwan between 2000 and 2015. Using multivariable Cox proportional hazard models, we estimated the hazard ratios and 95% confidence intervals for the correlation of skin cancer with organ transplantation as well as immunosuppressive regimen. Results Organ transplant recipients in Taiwan had an increased risk of skin cancer with adjusted hazard ratios of 4.327 (95% confidence intervals 2.740-6.837, P < 0.001), with the greatest risk, observed among heart recipients (adjusted hazard ratios 6.348, 95% confidence intervals 3.080-13.088, P < 0.001). The risk of non-melanoma skin cancer and melanoma was 4.473 (95% confidence intervals 2.568-7.783, P < 0.001) and 3.324 (95% confidence intervals 1.300-8.172, P < 0.001), respectively. When comparing immunosuppressants, those with calcineurin inhibitors carried the highest risk of skin cancer (adjusted hazard ratios 4.789, 95% confidence intervals 3.033-7.569, P < 0.001), followed by those with antimetabolites (adjusted hazard ratios 4.771, 95% confidence intervals 3.025-7.541, P < 0.001). Limitations We could not evaluate confounding behavioural risk factors of skin cancers that were not documented in the database, nor could we recognize patients' compliance with immunosuppressants. Conclusion Organ recipients have a greater risk of skin cancer. Clinicians should inform recipients of the importance of photoprotection and regular dermatologic follow-up.

LB904 Utilization of indoor tanning: A cross-sectional study using mobile device data

Indoor tanning using ultraviolet (UV) radiation increases skin cancer risk. However, there is little objective information on when or where indoor tanning is used. We aimed to evaluate tanning salon geography and patterns of use using objective data rather than self-report. We used data from SafeGraph, a company that combines smartphone location data and proprietary geographic data. Our dataset included aggregate, anonymous data from January 1, 2018-December 31, 2020. We developed and validated an algorithm (positive predictive value 92.6%) to identify businesses offering UV indoor tanning.

Zebrafish Syndromic Albinism Models as Tools for Understanding and Treating Pigment Cell Disease in Humans.

Melanin is the pigment that protects DNA from ultraviolet (UV) damage by absorbing excess energy. Melanin is produced in a process called melanogenesis. When melanogenesis is altered, diseases such as albinism result. Albinism can result in an increased skin cancer risk. Conversely, black pigment cell (melanocyte) development pathways can be misregulated, causing excessive melanocyte growth that leads to melanoma (cancer of melanocytes). Zebrafish is an emerging model organism used to study pigment disorders due to their high fecundity, visible melanin development in melanophores (melanocytes in mammals) from 24 h post-fertilization, and conserved melanogenesis pathways. Here, we reviewed the conserved developmental pathways in zebrafish melanophores and mammalian melanocytes. Additionally, we summarized the progress made in understanding pigment cell disease and evidence supporting the strong potential for using zebrafish to find novel treatment options for albinism.

Development of a Survey of Sunscreen Use and Attitudes among Adults in Two Coastal States, 2019

Skin cancer is the most common form of cancer in the United States, and regular use of broad-spectrum sunscreens can prevent skin cancer. However, a new law in Hawaii that limits sunscreen choices due to the belief that some UV (ultraviolet) filters may damage coral reefs may reduce sunscreen use and increase skin-cancer risk. Because of this, there is a need for measurement tools to help understand consumer behavior and determinants of sunscreen purchase and use. The objectives of this study were (1) to test new questionnaire measures relevant to the Hawaii Sunscreen Ban; and (2) to assess adults’ knowledge, attitudes, and habits related to sunscreen in two other coastal states. This survey of adult residents of California and Florida was conducted in the summer of 2019. Newly developed scales addressed beliefs about effects of sunscreens on aquatic/marine environments and awareness of the Hawaii sunscreen ban. Respondents completed the survey twice to evaluate the test–retest reliability. Respondents (n = 162) were mainly female, White, and college-educated. New scales had moderate-to-high internal consistency and high test–retest reliability. Sunscreen use was high, sunburn was common, and knowledge and attitudes about sunscreen were modest. Most respondents did not know the specifics of the Hawaii Sunscreen Ban. In multivariate models, significant predictors of sunscreen use were being older, female, and having higher sunscreen knowledge. Sunscreen beliefs were not significantly associated with sunscreen use or sunburn. The findings support the use of the newly developed survey and suggest that more education about sunscreen and sunscreen ingredients is needed.

The dark side of the sun: Affected demographics of skin cancers

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin malignancies. BCC and SCC are affecting the corresponding cells in the epidermis where tumorogenesis starts. The onset of these diseases is caused by sun exposure and ultraviolet radiation (UVR). However, it seems that there are more vulnerable groups within the population. Several other leading factors have been described in the literature. Elderly, male and fair-skinned individuals may have significantly increased skin cancer risk. Understanding the characteristics of these cancers epidemiology may allow their early detection and ensure better medical and surgical management. Keywords: Skin cancer risk; Ultraviolet radiation; Sun exposure; Sun protection; Review.

Ageing research: rethinking primary prevention of skin cancer.

Ageing research: rethinking primary prevention of skin cancer.

Cutaneous Malignancies After Kidney and Simultaneous Pancreas-Kidney Transplantations

Organ transplant recipients are at increased risk of nonmelanotic skin cancers (NMSC). Scarce data exist regarding secondary malignancies developing post-simultaneous pancreas-kidney (SPK) transplantations. Our aim was to assess long-term risk of skin cancers among kidney alone (KA) and SPK transplantation recipients. In this study, 521 patients who underwent KA or SPK transplantation at our medical center were observed up by dedicated nephrologists and dermatologists. SPK transplantation recipients were matched with a control group of KA transplantation recipients based on demographic and clinical data. A multivariate analysis was performed to find independent cancer risk factors. Patients who developed skin cancer were generally older, had a fair skin type, and had a higher incidence of NMSC before transplantation. Older age and fair skin type were independent risk factors on multivariate analysis. SPK transplantation in itself was not an independent risk factor. Cancer recurrence was associated with older age and male sex. Darker skin type and lowered immunosuppressive burden were protective. In contrast to previous studies, the use of antithymocytic agents or SPK transplantation were not independently associated with increased skin cancer risk in this multivariate analysis. These findings emphasize the complex interplay between posttransplantation NMSC and various clinical and epidemiologic risk parameters.

Photosensitizing Medications and Skin Cancer: A Comprehensive Review.

Simple SummaryPhotosensitizing medications are commonly used in the United States, and studies have begun exploring whether exposure to these medications may be a risk factor for skin cancer. As the population in the United States ages, there are more elderly patients being prescribed photosensitizing medications to treat chronic conditions. At the same time, the incidence of skin cancer is increasing. We summarize current evidence regarding the risk of skin cancer associated with use of each type of photosensitizing medication and highlight gaps in the literature to guide further study.(1) The incidence of skin cancer is increasing in the United States (US) despite scientific advances in our understanding of skin cancer risk factors and treatments. In vitro and in vivo studies have provided evidence that suggests that certain photosensitizing medications (PSMs) increase skin cancer risk. This review summarizes current epidemiological evidence on the association between common PSMs and skin cancer. (2) A comprehensive literature search was conducted to identify meta-analyses, observational studies and clinical trials that report on skin cancer events in PSM users. The associated risks of keratinocyte carcinoma (squamous cell carcinoma and basal cell carcinoma) and melanoma are summarized, for each PSM. (3) There are extensive reports on antihypertensives and statins relative to other PSMs, with positive and null findings, respectively. Fewer studies have explored amiodarone, metformin, antimicrobials and vemurafenib. No studies report on the individual skin cancer risks in glyburide, naproxen, piroxicam, chlorpromazine, thioridazine and nalidixic acid users. (4) The research gaps in understanding the relationship between PSMs and skin cancer outlined in this review should be prioritized because the US population is aging. Thus the number of patients prescribed PSMs is likely to continue to rise.

The Context of Sunburn Among U.S. Adults: Common Activities and Sun Protection Behaviors

Sunburn increases skin cancer risk and is common among U.S. adults. However, little is known about the contexts in which sunburns often occur. The purpose of this study is to examine the contextual factors surrounding sunburns among U.S. adults. Cross-sectional data from a 2018 online panel survey were analyzed. A total of 4,088 panel members were recruited by mail using probability-based, random sampling by address. Respondents were asked about their most recent sunburn, and analyses were limited to those who remembered their most recent sunburn (N=3,106). Data were weighted to match the U.S. Current Population Survey proportions; analyses were conducted in 2018 and 2019. Participants' age ranged from 18 to 93 years. About half (50.8%) were women, and most (82.3%) were non-Hispanic White adults. Swimming or spending time in water (32.5%), working outside at home (26.2%), traveling/vacationing (20.7%), and engaging in nonswimming physical activity (14.2%) were the most frequently reported activities. Using sunscreen on the face, neck, and chest (38.8%) and on the body (19.9%) and wearing sunglasses (34.2%) were the most frequently reported sun safety behaviors. Wearing clothes to the ankles (6.6%) and a long-sleeved shirt (4.5%) were least frequently reported. This study provides new information about the contexts in which adult sunburns often occur, especially about contexts unrelated to intentional tanning, which was relatively infrequent. The results suggest the need to promote multiple forms of sun protection tailored to specific outdoor activities and develop innovative solutions for outdoor physical and aquatic activities, which present unique sun safety challenges.