Risk Of Non-melanoma Skin Cancer Research Articles

The association between hydrochlorothiazide use and non-melanoma skin cancer in kidney transplant recipients

Abstract Background hydrochlorothiazide (HCTZ) diuretics were correlated with an increased risk of Non-Melanoma Skin Cancer (NMSC) and melanoma in the general population. Information is a scarce regarding this effect in Kidney transplant recipients who are at increased risk of skin malignancies under immunosuppression. Methods Single center retrospective analysis of adult kidney transplant recipients between January 1, 2010, and December 31, 2015. The primary outcome of the study was the first diagnosis of skin cancer that was removed and pathologically analyzed. Exposure to thiazides was defined as HCTZ use daily for at least one year at a dose of 12.5 mg. Results Among 520 kidney transplant recipients, 50 (9.4%) were treated with HCTZ. During a median follow-up of 9.8 years, 67 patients underwent surgical removal and pathological analysis of at least one skin cancer. Exposure to HCTZ during the three years following transplantation was associated with an increased risk of skin cancer (p=0.004). In a multivariate model, there was a significant association between HCTZ exposure and NMSC (HR 2.54, 95%CI 1.26-5.15, p=0.007). There was a higher rate of Basal Cell Carcinoma (BCC) with HCTZ exposure, according to both univariate and multivariate analyses (HR 2.61, 95%CI 1.06-6.43, p=0.037) and (HR 3.03, 95%CI 1.22-7.55, p=0.017, respectively). However, no significant association was observed between HCTZ exposure and Squamous Cell Carcinoma (SCC). Conclusions These findings suggest a benefit of increased frequency of dermatologist inspection in kidney transplant recipients receiving HCTZ especially in increased UV exposure area.

Skin cancers and their precursors in Finnish liver transplantation recipients: A follow‐up study

AbstractBackgroundThe incidence of skin cancers in transplant recipients is known to have increased compared to the general population. Risk factors include age at the time of transplantation, duration and dose of immunosuppressive medication. Research data on the incidence of skin cancer precursors in transplant recipients is limited.ObjectivesWe aimed to investigate the incidence of skin cancers and their precursors and the factors influencing their development in Finnish liver transplant recipients.MethodsWe recruited 140 volunteers who were over 18 years old at the time of the study and had been transplanted at least 5 years before. Patients were examined by a dermatologist between 2012 and 2016 and, if necessary, followed up based on cutaneous findings. All patients in the study were followed up until May 2021 or until the death of the patient, based on medical records.ResultsThe study found an increased incidence of nonmelanoma skin cancers (NMSCs), especially of squamous cell carcinoma, in liver transplantation (LT) recipients compared to the general Finnish population (squamous cell carcinoma SIR 21.2, basal cell carcinoma SIR 7.6). Precursors of squamous cell carcinoma were found in 43 patients (30.7%) after transplantation. The study found no statistically significant difference between the drugs used for immunosuppression.ConclusionsOur data showed an increased risk of NMSCs in LT recipients. After LT, patients are at significant risk of SCC and its precursors may be found even in almost third of patients in 17.5 years follow‐up. Given this information, it is considered important to monitor LTRs with adequate frequency to treat precursors as early as possible before the development of SCC.

Inflammatory Bowel Disease and Skin Cancer: A Two-Sample Mendelian Randomization Analysis.

Background: At present, numerous clinical studies suggest a correlation between inflammatory bowel disease (IBD) and skin cancer. However, some articles present differing views that IBD does not increase the risk of skin cancer. The presence of potential reverse causality and residual confounding is inherent in conventional observational studies. Thus, this study used a two-sample Mendelian randomization (MR) study design to estimate the causal effect of IBD on the risk of skin cancer, including cutaneous malignant melanoma (CMM, also named melanoma skin cancer) and nonmelanoma skin cancer (NMSC). Design: In this study, a two-sample MR analysis was used to estimate the causal effect of IBD on skin cancer outcomes. The inverse-variance weighted (IVW) method was used as the main MR analysis, with multiple sensitivity analyses conducted to assess the robustness of findings. Results: In examining the association between IBD and NMSC, all p-values of the IVW methods were found to be <0.05, providing evidence for a causal effect of IBD on an increased risk of NMSC. However, IVW for IBD on CMM yielded p-values >0.05, indicating no causal relationship between IBD and CMM. These findings were consistent across other MR methods, with no evidence of pleiotropy or heterogeneity. Sensitivity analyses confirmed the robustness of our results. Conclusion: Using MR analysis, we found evidence for a causal effect of genetic liability for IBD on an increased risk of NMSC. However, our study did not find sufficient evidence to support a significant impact of IBD on CMM outcomes.

Discrepancies in Non-Mohs Micrographic Surgery for Non-melanoma Skin Cancer Between Lighter-Skinned and Darker-Skinned Patients.

Non-melanoma skin cancer (NMSC) is highly prevalent in the United States, with darker-skinned patients (DSP) exhibiting lower incidence but increased morbidity and mortality. The purpose of this study is to elucidate NMSC disparities between DSP (Fitzpatrick skin phototype IV or more) and lighter-skinned patients (LSP, Fitzpatrick skin phototype III or less), focusing on surgical features of non-Mohs micrographic surgery-treated NMSC. This retrospective cohort study included LSP and DSP diagnosed with either basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in an academic dermatology setting. Variables collected included age, gender, type of NMSC, location, staging, time-to-diagnosis (TTD), pre-operative lesion size, and post-operative defect size. Categorical variables were reported as counts and percentages, while the association between categorical variables was assessed using a two-tailed Fisher's test. A paired t-test was used to determine the association between continuous variables. P-values <0.05 were considered statistically significant. A total of 27 patients with NMSC were identified, of which 9 (33.3%) were DSP. Patients of darker skin were predominantly female (n=7; 77.8%), while no gender predilection was found in LSP (n=9; 50.0% female; p=0.23). Time-to-diagnosiswas significantly longer inDSP than in LSP (61.3 weeks vs 25.1 weeks, respectively; p = 0.02). Despite this, there was no statistical difference in terms of staging, pre-operative lesion size (11.89 mm in DSP vs 10.76 mm in LSP, p=0.75), and post-operative defect size (45.56 ± 29.21 mm in DSP vs 31.22 ± 19.60 mm in LSP; p=0.33). Darker-skinned patients had a longer TTDwithout staging differences. Our study confirms the need for reducing TTDs for NMSC in DSP. Action initiatives include continued educational efforts to increase awareness of NMSC risk in DSP and more rigorous routine skin cancer screening.

Role of Insulin Use and Social Determinants of Health on Non-melanoma Skin Cancer: Results From the Behavioral Risk Factor Surveillance System.

Non-melanoma skin cancer (NMSC) is a frequent type of malignancy with a steadily increasing incidence rate worldwide. Although NMSC was shown to be associated with diabetes, no studies have addressed the extent to which insulin use influences the risk of NMSC in light of social determinants of health (SDOH). We conducted a quantitative study that examined the interplay between insulin use, SDOH, additional covariates, and NMSC among individuals with diabetes. We based our analysis on the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a national survey conducted yearly in the US. We performed weighted chi-squared test, logistic regression, and survival analyses on 8685 eligible participants with diabetes enrolled in the BRFSS. Kaplan Meier survival curves showed higher probability of NMSC event-free survival for participants with diabetes using insulin compared to participants with diabetes not using insulin (log-rank test P < .001). Significant associations were detected between insulin use and reduced odds of NMSC (OR .56; 95% CI: .38-.82), and decreased hazard (HR .36; 95% CI: .21-.62), along with indices of SDOH. Our findings suggest that socioeconomic differences related to the healthcare system and behavioral patterns are linked to discrepancies in the use of insulin and the development of NMSC.

The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis.

Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products. It participates in cellular energy metabolism and modulates multiple cellular survival and death pathways. Nicotinamide has been widely studied as a safe chemopreventive agent that reduces actinic keratosis (AKs) and non-melanoma skin cancers (NMSC). We used the Medline, EMBASE, PubMed, and Cochrane databases to search the concepts "nicotinamide", "chemoprevention", and "skin cancer" up to August 2023. Three independent authors screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. The primary outcome was the impact of oral nicotinamide on the incidence of NMSC in high-risk patients. We also conducted a systematic search to identify relevant epidemiological studies published evaluating dietary niacin intake and the risk of NMSC. Two hundred and twenty-five studies were reviewed, and four met the inclusion criteria. There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48-1.37; I2 = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50-1.55; I2 = 63%), and NMSC (RR 0.82, 95% CI 0.61-1.12; I2 = 63%). Adverse events were rare and acceptable, allowing optimal compliance of patients to the treatment. We found only one article evaluating the association between niacin dietary intake and NMSC risk, supporting a potential beneficial role of niacin intake concerning SCC but not BCC or melanoma. The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.

The Association of Vitamin D with Non-Melanoma Skin Cancer Risk: An Umbrella Review of Systematic Reviews and Meta-Analyses.

Background and Objectives: Previous studies revealed the anti-angiogenic, antiproliferative, and anti-inflammatory effects of Vitamin D (VitD) on cancer cells. Although this body of evidence supported the correlation of high VitD levels with reduced incidence rates for various malignancies, contradictory results were reported regarding non-melanoma skin cancer (NMSC). The aim of this overview was to summarize the available evidence from the existing pool of systematic reviews and meta-analyses, focusing on VitD serum status, dietary intake, and VitD receptor (VDR) polymorphisms in correlation to NMSC incidence. Materials and Methods: A literature search in electronic databases was conducted from inception to January 2023. The inclusion criteria were systematic reviews and meta-analyses published in peer-reviewed journals, evaluating VitD serum levels, dietary and/or supplementary intake, or VDR gene polymorphisms, and reporting data on NMSC. Results: A total of 10 studies were included in the data analysis models. A positive association between VitD serum levels and NMSC is highlighted. However, dietary/supplementation of VitD does not exhibit a likewise strong linkage to NMSC. Despite the contradictory findings, VDR polymorphisms may play a crucial role in the intricate NMSC pathogenesis. Conclusions: This umbrella review shows that high VitD levels are associated with increased NMSC incidence, potentially due to its direct correlation with increased sun exposure. Further research on VDR polymorphisms is suggested to explore their true effect size on NMSC risk.

Revisiting the safety profile: Understanding the link between Methotrexate and skin cancer in psoriasis patients

Madam, Methotrexate (MTX) is an antimetabolite (formerly known as amethopterin) proven t effective in managing autoimmune diseases by suppressing the hyperactive immune response, reducing inflammation, and alleviating associated symptoms. In the case of psoriasis, a chronic autoimmune skin disorder characterized by red, scaly patches on the skin, MTX is among the available treatment options. It is proven beneficial for moderate to severe psoriasis that does not respond adequately to other treatments by reducing the severity and extent of the skin lesions, relieving itching, and improving the overall quality of life. A recent study by Ravi Bharadwaj et al. found that MTX exerts its therapeutic effect on psoriatic skin inflammation by inhibiting the activity of the muropeptide transporter SLC46A21. This mechanism interferes with two key inflammatory responses, namely the NOD1 and NOD2 pathways. It is administered orally, intramuscularly, intravenously, or subcutaneously. Doctors opt for a once-weekly oral dosage, which initiates at a low level to minimize adverse effects. Subsequently, the dosage is incrementally raised to attain the desired efficacy2. Although MTX can be an effective treatment choice, its usage has raised concerns regarding the potential elevation of skin cancer risk. In recently published studies, researchers have concluded that the use of this drug in psoriatic patients might be doing more harm than good. In a meta-analysis performed by Margaret et al., It was found that psoriasis patients receiving MTX therapy have a 2.8-fold greater likelihood of developing non-melanoma skin cancer (NMSC) in comparison to those who do not undergo MTX treatment3. Moreover, there is evidence that prolonged use of MTX may be associated with an increased probability of developing basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), following a dose-dependent trend4. Individuals with psoriasis who may require long-term systemic treatment could face a significantly elevated risk of developing skin cancer. Despite multiple studies confirming the link between MTX and different skin malignancies, its usage remains alarmingly high in treating psoriasis. In resource-limited settings such as Pakistan, this drug is a cost-effective and efficient therapeutic option for managing various forms of psoriasis, including extensive plaque-type psoriasis, acute pustular psoriasis, and erythrodermic psoriasis5. Nevertheless, healthcare workers in Pakistan must prioritize establishing an accurate drug administration plan, to reduce morbidity and mortality rates, as well as the heightened risk of non-melanoma skin cancer (NMSC) among psoriasis patients receiving this treatment.

Prevalence of Second Cancers in Patients with Polycythemia Vera (PV): A Retrospective Analysis of US Real-World Claims Data

Background:Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) associated with risk of leukemic or fibrotic progression (Tefferi and Barbui. Am J Hematol. 2017;92;94-108). In addition to the known risk of disease transformation, patients with MPNs have a 60% higher risk of developing second non-hematologic cancers compared to matched controls. Skin cancers are among the most prevalent second cancers, with a reported 2.8-fold increase in risk of non-melanoma skin cancer (NMSC) (Landtblom et al., Leukemia. 2018;32:2203-10). The inherent risk associated with MPNs is exacerbated by cytoreductive treatments, as patients treated with hydroxyurea (HU) were found to have a two-fold higher risk of NMSC compared to patients who were not treated with HU (Barbui et al., Leukemia. 2019;33:1996-2005). Previous studies examined fewer than 2000 patients; the study populations may have included patients with other MPNs and PV. Our objective was to evaluate the frequency of second cancers in patients with a primary PV diagnosis who were treated with HU compared to phlebotomy only using a large US real-world claims database. Methods:This real-world, retrospective cohort study used Optum's deidentified Market Clarity Data consisting of electronic health records (EHR) on 105 million US patients and linked medical and prescription claims between 1/1/2007 to 12/31/2019. More than 82,000 patients with ≥1 PV diagnosis at any time were identified within the extracted dataset. For this analysis, eligible patients were ≥18 years old and required ≥2 PV diagnosis codes with ≥60 days between the first and last diagnosis code in the data period. Patients were indexed at the first diagnosis code of PV preceded by ≥1 year of EHR data (“index”) and required ≥1 year of post-index data or death prior to data period end. Patients with a pre-index diagnosis of secondary polycythemia, leukemia, myelodysplastic syndrome, myelofibrosis, or stem cell transplant were excluded. Second cancers were identified at first occurrence of a diagnosis code for a defined cancer in EHR during specified time periods. Analysis of post-treatment cancer rates used a subset of patients with pre-index medication data and excluded cancer types identified prior to treatment. Results:The total study cohort included 20,089 patients with PV (mean age, 63.0 years; 57.8% male; 88.6% Caucasian). Some patients (15.5%; n=3112) had evidence of a pre-index cancer. Median duration of follow-up was 4.3 years (IQR, 2.4-5.9). Among the total cohort, 35.7% (7181 patients) reported at least one second cancer in the post-index period (“post-index period prevalence”). The rate of second cancers in the post-index period was 109.7 events per 1000 patient years (PY). The most common non-hematologic malignancies were skin cancers (22.1/1000 PY) followed by prostate cancer (8.1/1000 PY) and breast cancer (6.7/1000 PY) (Figure 1). Within the total cohort, 9.1% (1830 patients) reported at least one skin cancer in the post-index period, with 8.3% (1659 patients) experiencing NMSC and 1.4% (286 patients) experiencing melanoma (Figure 1). The post-index period prevalence rate of NMSC was 6 times higher vs. the rate of melanoma (19.8 vs. 3.3/1000 PY). Among NMSCs, the rate of basal cell carcinoma was higher than the rate of squamous cell carcinoma (8.7 vs. 6.9/1000 PY). However, the highest rate was observed for non-specific or unspecified malignant neoplasms (8.9/1000 PY). Within a subset of 17,402 patients with pre-index medication data, 20.2% (n=3512) were exposed to at least 4 weeks of HU (without ruxolitinib) at any time; 19.0% (n=3314) were treated with phlebotomy (PHL) only. The rate of any second malignancy subsequent to treatment was &amp;gt;2.5-times higher in the HU vs. PHL group (140.4 vs. 55.3/1000 PY) (Table 1). Rates of skin cancers were nearly two times higher in the HU vs. PHL group for any skin cancer (31.6 vs. 17.7/1000 PY), NMSC (28.9 vs. 15.7/1000 PY), and melanoma (4.5 vs. 2.9/1000 PY). Conclusion:To our knowledge, this is the largest retrospective study evaluating the frequency of second cancers in a cohort of US patients with PV to-date. We found that patients with PV had high rates of malignancies associated with their primary PV diagnosis. The highest rates were observed for skin cancers, driven by the frequency of NMSC. Patients treated with HU had nearly twice the rate of skin cancers (including NMSC and melanoma) compared to PHL-only treated patients.

Childhood sunburn and risk of melanoma and non-melanoma skin cancer: a Mendelian randomization study

Previous evidence has suggested that childhood sunburn could be a risk factor for cutaneous malignant melanoma (MM) and non-melanoma skin cancer (NMSC). However, existing observational studies could not reveal the causal associations genetically. This study aimed to investigate whether there was a genetic causal relationship between childhood sunburn and skin cancers. Univariable Mendelian randomization (MR) and Causal Analysis Using Summary Effect analysis was carried out for causal estimates and evaluation for the horizontal pleiotropy. Multivariable MR and the mediation effects analysis were used to test whether the causal associations were mediated by potential confounders. A suggestively significant causal association between childhood sunburn and MM was indicated (OR = 4.74; 95% CI: 1.31–17.19; p = 1.79E-02). Genetically predicted childhood sunburn was significantly associated with increased risk of overall melanoma in situ (MIS) (OR = 4.02; 95% CI: 2.00–8.08; p = 9.40E-05), MIS of face (OR = 18.28; 95% CI: 5.28–63.35; p = 4.59E-06), and MIS of trunk (OR = 7.05; 95% CI: 2.06–24.13; p = 1.88E-03). Similar trends were found for childhood sunburn and NMSC (OR = 8.16; 95% CI: 6.07–10.99; p = 1.53E-20), including both basal cell carcinoma (BCC) (OR = 3.76; 95% CI:2.96–4.77; p = 2.19E-08) and squamous cell carcinoma (SCC) (OR = 7.44; 95% CI: 5.09–10.87; p = 2.19E-08). After adjustment for hair and skin color, facial ageing, vitamin D levels, body mass index, alcohol consumption, and smoking status, childhood sunburn showed an independent association with MIS, MIS of face, MIS of trunk, as well as NMSC, including both BCC and SCC. Mediation analysis showed no significant mediation effect. This study demonstrated a causal relationship between childhood sunburn and the risk of both MM and NMSC, which suggested that enhanced screening and prevention for childhood sunburn could contribute to the early detection and decreased risk of MM and NMSC.

Glucagon like peptide-1 receptor agonists and the risk of skin cancer among patients with type 2 diabetes: Population-based cohort study.

The objective of this study was to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is associated with an increased risk of melanoma and nonmelanoma skin cancer, separately, compared with the use of sulfonylureas among patients with type 2 diabetes. Using the United Kingdom Clinical Practice Research Datalink (2007-2019), we assembled two new-user active comparator cohorts. In the first cohort assessing melanoma as the outcome, 11,786 new users of GLP-1 RAs were compared with 208,519 new users of sulfonylureas. In the second cohort assessing nonmelanoma skin cancer as the outcome, 11,774 new users of GLP-1 RAs were compared with 207,788 new users of sulfonylureas. Cox proportional hazards models weighted using propensity score fine stratification were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma and nonmelanoma skin cancer, respectively. Compared with sulfonylureas, GLP-1 RAs were not associated with an increased risk of either melanoma (42.6 vs. 43.9 per 100,000 person-years, respectively; HR 0.96, 95% CI 0.53-1.75) or nonmelanoma skin cancer (243.9 vs. 229.9 per 100,000 person-years, respectively; HR 1.03, 95% CI 0.80-1.33). There was no evidence of an association between cumulative duration of use with either melanoma or nonmelanoma skin cancer. Consistent results were observed in secondary and sensitivity analyses. In this population-based cohort study, GLP-1 RAs were not associated with an increased risk of melanoma or nonmelanoma skin cancer, compared with sulfonylureas.

Abatacept and non-melanoma skin cancer in patients with rheumatoid arthritis: a comprehensive evaluation of randomised controlled trials and observational studies

ObjectivesThis study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA).MethodsThis evaluation included 16 abatacept RA clinical trials and 6 observational studies. NMSC...

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000–2019: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

BackgroundA World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. MethodsWe calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO’s estimates of the total NMSC burden. Measures of inequality were calculated. ResultsGlobally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6–1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9–28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7–35.0) for NMSC deaths and 30.4 % (UR 29.0–31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180–19,740) and 0.5 million DALYs (UR 0.4–0.5). Men and older age groups carried larger burden. Over 2000–2019, attributable deaths and DALYs almost doubled. ConclusionsWHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.

Immunity against Non-Melanoma Skin Cancer and the Effect of Immunosuppressive Medication on Non-Melanoma Skin Cancer Risk in Solid Organ Transplant Recipients.

Non-melanoma skin cancers (NMSCs) occur frequently in the Caucasian population and are considered a burden for health care. Risk factors include ultraviolet (UV) radiation, ethnicity and immunosuppression. The incidence of NMSC is significantly higher in solid organ transplant recipients (SOTRs) than in immunocompetent individuals, due to immunosuppressive medication use by SOTRs. While the immunosuppressive agents, calcineurin inhibitors and purine analogues increase the incidence of NMSC in transplant recipients, mTOR inhibitors do not. This is most likely due to the different immunological pathways that are inhibited by each class of drug. This review will focus on what is currently known about the immune response against cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), two of the main types of NMSC. Furthermore, we will describe the different classes of immunosuppressants given to SOTRs, which part of the immune system they target and how they can contribute to NMSC development. The risk of developing NMSC in SOTRs is the result of a combination of inhibiting immunological pathways involved in immunosurveillance against NMSC and the direct (pro/anti) tumor effects of immunosuppressants.

Exogenous hormone therapy and non-melanoma skin cancer (keratinocyte carcinoma) risk in women: a systematic review and meta-analysis

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.

Incidence of melanoma and non-melanoma skin cancer in patients with celiac disease: a systematic review and meta-analysis.

There is conflicting observational evidence regarding the association between skin cancer and celiac disease (CD). The purpose of this review was to investigate the incidence rate ratio (IRR) of skin cancer incidence between patients with and without CD. MEDLINE and EMBASE databases were searched on October 27th, 2021 and eight articles were identified for review. Quality assessment was conducted using the Newcastle Ottawa Scale. Seven articles were included in meta-analysis for a pooled estimate of IRR across all skin cancers, malignant melanoma (MM), and non-melanoma skin cancers (NMSC). In total, 74,860 CD patients were followed for 710,214 person-years in the meta-analysis. Overall combined incidence was 99.8 cases per 100,000 person-years. Meta-analysis of all skin cancer incidence showed no significant difference in CD patients compared to controls (IRR: 1.06; 95% CI: 0.95, 1.17; p=0.29; I2: 0%). Five studies reported on MM incidence; there was no significant difference in incidence compared to controls (IRR: 0.87, 95% CI: 0.72, 1.06; p=0.22; I2: 9%). Five studies reported on NMSC incidence, revealing a significantly increased risk of NMSC in CD patients (IRR: 1.14; 95% CI: 1.01, 1.28; p=0.04; I2: 0%). Our findings suggest a significantly increased incidence of NMSC in CD patients compared to control data and no significant association between CD and MM incidence. The findings are limited by the quantity and quality of the evidence. Nonetheless, clinicians should emphasize the importance of sun protection, such as sunscreen usage and self-examination for patients with CD.

B-223 Validation of a Non-invasive DNA NGS Assay for Detecting Somatic Mutations in Normal Appearing Sun Exposed Skin

Abstract Background Ultraviolet radiation (UVR) exposure is a major risk factor for developing nonmelanoma skin cancer and somatic mutations caused by UVR exposure can arise even in normal-appearing skin. Non-invasive identification of UVR induced somatic mutations can provide a quantitative evaluation of the extent of UVR damage. This study describes the development and analytical validation of a noninvasive method for identifying low level somatic variants in sun exposed peripheral skin by ultra-deep Next Generation Sequencing, in specimens collected using adhesive tape designed to non-invasively collect skin samples. Methods Five genomic regions with the highest density of known UVR induced somatic mutations across TP53 and NOTCH1 were amplified by 5-plex PCR primers affixed with Illumina NGS adapters. These amplicons were purified, size selected and then indexed using Unique Dual Indexes. The NGS libraries were pooled to 96-plex and bi-directionally sequenced with 2x150 chemistry on the Illumina iSeq100. Data analysis was performed using the Illumina DRAGEN Somatic Variant Calling pipeline. Titrations between 0.01 and 1 of synthetic controls comprising plasmids containing amplimer inserts with 19 of the most well characterized UVR-induced C &amp;gt; T driver mutations spiked into a wildtype insert were sequenced in duplicate. In addition, 3 cell line controls at input concentrations of a 2-fold serial dilution from 13.2 ng–0.4 ng were spiked into a mutation negative cell line at variant allele frequencies between 0.005 and 1 and sequenced in triplicate across three NGS runs. Finally, 178 specimens collected from the central forehead, nose and cheeks of human donors were sequenced and their cumulative mutation frequency analyzed by linear regression against the age of the participants. Results All samples were sequenced to a mean duplex coverage of &amp;gt;10000×. All expected mutations in the plasmid control titrations were identified for each titration. Both reproducibility and specificity in these samples were 1.0. The cell line controls were sequenced in a matrix of DNA input concentration vs Variant Allele Frequency (VAF). The Limit of Detection for the assay was a function of DNA concentration, with 0.4ng, 0.8ng and 3.3ng DNA required to identify mutations accurately and reproducibly at 0.05, 0.02 and 0.01 VAF respectively. The study found that the mutations detected among the human donor samples strongly correlated cumulative VAF with age (P value = 2.56×10−7). Conclusion This study describes the validation of a method for identifying low frequency variants in sun exposed skin. We demonstrate that the assay is a robust and reliable tool for detecting TP53 and NOTCH1 somatic variants associated with UVR exposure in normal-appearing skin down to 0.01 VAF with &amp;gt;0.8 sensitivity, specificity, and reproducibility. Damage from UV exposure is cumulative and therefore it is expected that older individuals will be more likely to have UVR-induced mutations in their skin, as we observed in this analysis. The assay can detect somatic DNA variations in normal-appearing skin for markers that are associated with UV damage and increased overall risk for certain nonmelanoma skin cancers.

Second primary malignancies in patients with lymphoma in Denmark after high-dose chemotherapy and autologous haematopoietic stem-cell transplantation: a population-based, retrospective cohort study

Second primary malignancies (SPMs) are known complications after chemotherapy, but the risk is not well characterised for patients with lymphoma treated with high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the rate of SPMs in this population relative to matched control individuals from the general population. In this retrospective, population-based cohort study, patients aged 18 years or older with an aggressive lymphoma who received high-dose chemotherapy and autologous HSCT in Denmark between Jan 1, 2001, and Dec 31, 2017, were included from the Danish Lymphoma Registry and matched (1:5) to control individuals from the general population on birth year and sex via the Danish Civil Registration System. Patients were eligible if they had a registered date of autologous HSCT and patients with primary CNS lymphoma were excluded. Exclusion criteria for both patients and matched control individuals were HIV infection, organ transplantation, or other malignancies before inclusion. The key endpoint was the incidence of SPMs assessed in all study participants. The effect of treatment on SPMs was also investigated in patients who were followed up from first lymphoma diagnosis, with high-dose chemotherapy and autologous HSCT as a time-dependent exposure. Of 910 patients with lymphoma assessed, 803 were included (537 [67%] were male and 266 [33%] were female); 4015 matched control individuals were included (2685 [67%] were male and 1330 [33%] were female). Ethnicity data were not available. Median follow-up was 7·76 years (IQR 4·77-11·73). The SPM rate was higher among patients receiving high-dose chemotherapy and autologous HSCT than matched control individuals (adjusted hazard ratio [HR] 2·35, 95% CI 1·93-2·87, p<0·0001). Patients receiving high-dose chemotherapy and autologous HSCT had a higher rate of non-melanoma skin cancer (2·94, 2·10-4·11, p<0·0001) and of myelodysplastic syndrome or acute myeloid leukaemia (AML; 41·13, 15·77-107·30, p<0·0001) than matched control individuals, but there was no significant difference in the rate of solid tumours (1·21, 0·89-1·64, p=0·24). The cumulative risk of SPMs at 10 years was 20% (95% CI 17-23) in patients compared with 14% (13-15) in matched control individuals. High-dose chemotherapy and autologous HSCT was associated with an increased risk of SPMs when analysed as a time-dependent exposure from first lymphoma diagnosis (adjusted HR 1·58, 95% CI 1·14-2·17, p=0·0054). High-dose chemotherapy and autologous HSCT was associated with an increased risk of non-melanoma skin cancer and myelodysplastic syndrome or AML but not with increased risk of solid tumours in patients treated for lymphoma. These findings are relevant for future individualised risk-benefit assessments when choosing between high-dose chemotherapy and autologous HSCT and chimeric antigen receptor T-cell therapy in this setting. Danish Cancer Society.

44164 Comparative Risk of Non-Melanoma Skin Cancer Associated with Prior Use of Ingenol Mebutate vs Imiquimod

44164 Comparative Risk of Non-Melanoma Skin Cancer Associated with Prior Use of Ingenol Mebutate vs Imiquimod

JAAD Game Changer: “Effect of voriconazole on risk of nonmelanoma skin cancer after hematopoietic cell transplantation”

JAAD Game Changer: “Effect of voriconazole on risk of nonmelanoma skin cancer after hematopoietic cell transplantation”