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Background: While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute. This study aimed to investigate the association of BCC and exposome-related factors in the Spanish population., Methods: BCC cases (n = 119) and controls (n = 127) with no history of skin cancer were recruited between April 2020 and August 2022 by 13 dermatologists throughout Spain in this prospective multicenter case-control study., Results: The BCC group had a higher proportion of outdoor workers, more years of UVR exposure, and a greater consumption of drugs (statins, ASA, hydrochlorothiazide, ACE inhibitors and omeprazole), P < 0.05. Avoidance of sun exposure was the most used photoprotection measure in both groups. The use of hats or caps was higher in the BCC group (P = 0.01). The solar protection factor (SPF) used 15 years previously was higher in the control group (P = 0.04). The control group had a higher daily screen time (P < 0.001), and practiced more relaxation activities (P = 0.03). Higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with BCC (P < 0.05). Statistical significance for all the aforementioned variables was maintained in the multivariate analysis (P < 0.05)., Conclusions: The study found a significant association between BCC and multiple exposome-related factors in addition to chronic sun exposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers, promoting sun-safe behaviors and stress-reducing activities, and also adequate skin photoprotection in patients on certain medications associated with increased BCC risk., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Competing Interests: Conflicts of interest None disclosed.

Background: Here we report clinical risk factors and event rates for the development of new non-melanoma skin cancer (NMSC) in a randomized, double-blind, placebo-controlled trial of the irreversible ornithine decarboxylase (ODC) inhibitor, difluromethylornithine (DFMO), over a 3-5-year follow-up., Methods: 147 placebo patients (white; mean age 60.2 years; 60% male) were evaluated for event rates and association of initial skin biomarkers and baseline patient characteristics with the development of squamous cell (SCC) and basal cell (BCC) carcinomas., Results: Post-study evaluation (median follow-up 4.4 years) indicates the measures of prior NMSCs ( P  ≤ 0.001), prior BCCs ( P  ≤ 0.001), prior SCCs ( P  = 0.011), prior tumor rate ( P  = 0.002), hemoglobin ( P  = 0.022), and gender ( P  = 0.045) as significant predictors for new NMSC development. Similarly, all measures of prior BCCs and NMSCs ( P  < 0.001), prior tumor rate ( P  = 0.014), and SCCs in the prior 2 years ( P  = 0.047) were statistically significant predictors for new BCC development. Total prior NMSCs and those in the prior 5 years ( P  < 0.001), total prior SCCs and those in the prior 5 years ( P  < 0.001), total prior BCCs and those in the prior 5 years ( P  ≤ 0.001), prior tumor rate ( P  = 0.011) as well as age ( P  = 0.008), hemoglobin ( P  = 0.002), and gender ( P  = 0.003) were statistically significant predictors of new SCC development. TPA-induced ODC activity at baseline showed no statistically significant association with the development of new NMSC ( P  = 0.35), new BCCs ( P  = 0.62), or new SCCs ( P  = 0.25)., Conclusion: In the studied population, the history of and rate at which prior NMSCs occur are predictive and should be controlled for in future NMSC prevention trials., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The exploration of molecular genetic mechanisms that underlie carcinogenesis, hereditary factors of various oncological diseases, including basal cell carcinoma, the most common type of skin cancer is especially actual and significant for target strategies of public health. The diagnosis of basal cell carcinoma is based on complex clinical, radiologic and genetic examination data. The further research in the field of somatic or hereditary mutations in genes associated with basal cell carcinoma, including Patched 1 (PTCH1), Patched 2 (PTCH2), Smoothed (SMO) continue to be topical. The strategies of primary prevention of basal cell carcinoma, discussions of complex issues of decision-making concerning treatment at primary health care level, training courses and development of guidelines for general practitioners and interdisciplinary recommendations for effective early diagnosis and comprehensive care of basal cell carcinoma are to be suggested.

Background: While skin cancer awareness programs have significantly furthered public understanding about the harmful effects of the sun, there is a disparity between photoprotection knowledge and protection practices., Objective: To compare sun exposure habits and photoprotection measures in patients diagnosed with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma versus controls., Methods: Multicentre case-control observational study carried out by 13 Spanish dermatologists between April 2020 and August 2022. Patients diagnosed with BCC, SCC, or melanoma were considered cases. The control group consisted of individuals with no history of skin cancer., Results: Of the 254 cases (56.2% female; mean age, 62.67 ± 15.65), 119 (31.2%) had BCC, 62 (16.27%) SCC, and 73 (19.1%) melanoma. The control group consisted of 127 (33.33%) individuals. Avoiding sun exposure between 12:00 and 16:00 was the most commonly used photoprotection measure (habitually/always: 63.1%), followed by the use of sunscreen (habitually/always: 58.9%). Patients with melanoma were less likely to use clothing and shade to avoid sun exposure (p < .05), whereas those with BCC and SCC reported greater use of head coverings (p = .01). BCC and SCC groups reported greater sun exposure 15 years prior, whereas controls reported greater use of sunscreen. However, at the time of this study all groups reported using SPF ≥ 21, and the majority SPF > 50. No differences were observed in photoprotection measures between people with and without a previous history of skin cancer., Conclusions: We describe differences in photoprotection measures and sun exposure patterns among patients diagnosed with different skin tumor types. Whether these differences may influence the type of tumor each developed will require further investigation., (© 2023 The Authors. Photodermatology, Photoimmunology & Photomedicine published by John Wiley & Sons Ltd.)

Background: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B 3 ) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear., Methods: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life., Results: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups., Conclusions: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.)., (Copyright © 2023 Massachusetts Medical Society.)

The most recent data relating to the incidence of, and mortality from, the three commonest forms of skin cancer, namely basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous melanoma (CM), in the Black African, Colored, Asian/Indian and White population groups in South Africa are reviewed. While exposure to solar ultraviolet radiation is the major environmental risk factor for BCC in all four groups, for SSC in the White and Asian/Indian groups and for CM in the White group, this is unlikely to be the case for most SCCs in the Black African group and for most CMs in the Black African and Asian/Indian groups. Strategies for practical personal photoprotection in South Africa are discussed with particular emphasis on people at heightened risk of skin cancer including the White population group, those with HIV or oculocutaneous albinism and outdoor workers., (© 2022 American Society for Photobiology.)

Non-melanoma skin cancer (NMSC) is the most common cancer among white-skinned people. The main environmental risk factor for all types of skin cancer is ultraviolet (UV) exposure to the sun. However, significant modifiable risk factors, such as diet, have been studied about NMSC risk. Several original studies have been conducted on the link between various dietary components and the risk of NMSC in the past decade, but have not been systematically reviewed. This review focuses on the potential impact of dietary components in the prevention of NMSC and evaluates the findings of epidemiologic evidence for dietary factors. We conducted a systematic search of three databases, including Scopus, ISI Web of Science, and PubMed, to identify relevant epidemiological studies published between 2000 and July 6, 2021. Finally, forty-three articles were included. Because of the inherent limitations of epidemiological studies, no definitive conclusions can be drawn; however, the links between folate, citrus, caffeine, and alcohol with BCC are notable; thus, high dietary folate intake, as well as citrus and alcohol consumption, are associated with an increased risk of basal cell carcinoma (BCC), whereas caffeine is associated with a lower risk. More research is required to reach a definitive conclusion.

Background: Prevention campaigns for skin cancers have focused primarily on melanoma, and over time there has been increasing awareness of the need to select the population to be screened to maximize program effectiveness., Objectives: The objective of the study was to report the results of a free dermatological initiative, as part of an awareness campaign dedicated to keratinocyte cancers, targeting individuals pre-selected through a short questionnaire., Methods: One day of dermatological consultations was held at 15 dermato-oncology referral centers during May 22-June 30, 2021. For selection, individuals answered a telephone interview consisting of 7 yes/no questions on risk factors. Demographics, clinical characteristics of suspicious tumors, and histopathologic diagnosis of excised lesions were collected. Suspicion rate, detection rate, and positive predictive values (PPVs) for any skin cancer, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma were calculated., Results: A total of 320 individuals (56.9% males; 43.1% females) with a median age of 69.6 (range 21-91) years qualified for the screening initiative. Overall, skin cancers and precancerous lesions were diagnosed in 65.9% of the patients. Suspicion rate was 28.7% for any skin cancer (92/320), 22.8% for BCC (73/320), 4.7% for cSCC (15/320), and 1.2% for melanoma (4/320). Detection rate was 23.4% for any skin cancer (PPV 93.7%), 18.1% for BCC (PPV 95.1%), 4.4% for cSCC (PPV 93.3%), and 0.9% for melanoma (PPV 75%)., Conclusions: Selection of individuals at high risk is a cost-effective approach for early detection campaigns for keratinocyte cancers., (© 2023 S. Karger AG, Basel.)

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

Immunosuppressive agents are essential for graft survival in solid-organ transplant recipients (SOTRs), but they have substantial durable side effects, including a higher incidence of aggressive nonmelanoma skin cancers (NMSCs). Hitherto, only one class of immunosuppressants, mammalian target of rapamycin inhibitors (mTORi), may inhibit skin tumor formation, however their durable effectiveness is controversial. To evaluate the sustained effectiveness of mTORi in reducing NMSCs' incidence in SOTRs, a retrospective study was conducted in a specialized dermatology clinic for SOTRs of a tertiary university-affiliated medical center. SOTRs with a history of at least one histologically proven NMSC were followed for 6 years: 3 years after transplantation, before initiation of mTORi, and 3 years under mTORi treatment. The cohort consisted of 44 SOTRs. Treatment with mTORi was initiated on average 6.27 (3.34-6.34) years following transplantation. In the 3 years before mTORi treatment initiation, the mean number of new NMSCs per patient was 2.11 (1-14). This value decreased to 1.2 (0-19) in the 3 years under mTORi treatment (p = 0.0007). Analysis by NMSC type yielded a significant decrease in both SCCs and BCCs. This study found that mTORi are effective for prolonged secondary prevention of NMSCs in SOTRs., (© 2022 Wiley Periodicals LLC.)

Purpose: Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate the associations between antioxidant supplement intake and keratinocyte cancer (KC) risk., Methods: E3N is an ongoing prospective cohort initiated in 1990 and involving 98,995 French women aged 40-65 years at recruitment. Intakes of dietary antioxidants were estimated via a validated dietary questionnaire in 1993 and self-reported antioxidant supplement use was collected in 1995. We used Cox models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and skin cancer risk factors., Results: Over 1995-2014, 2426 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KC risk (HR = 1.37, 95% CI 1.15-1.62), particularly with BCC (HR = 1.40, 95% CI 1.17-1.69); and between vitamin E supplement use and risks of both BCC (HR = 1.21, 95% CI 1.03-1.52) and SCC (HR = 1.43, 95% CI 1.03-1.99). Intake of beta-carotene supplements was associated with an increased SCC risk (HR = 1.59, 95% CI 1.00-2.54). Vitamin C supplement use was not associated with KC risk. We found similar results when considering total antioxidant intake., Conclusions: Intakes of vitamin A or E supplements were associated with an increased KC risk in women. Further studies with information on doses and duration of supplement use and the ability to examine their underlying mechanisms are needed., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The factors (environmental and genetic) contributing to basal cell carcinoma (BCC) pathogenesis are well-established; however, effective agents for BCC prevention are marred by toxic side-effects. Herein, we assessed the efficacy of flavonolignan silibinin against ultraviolet B (UVB)-induced BCC in Ptch+/- (heterozygous patched homolog 1 gene) mouse model. Both male and female Ptch+/- mice were irradiated with a 240 mJ/cm2 UVB dose 3 times/week for 26 or 46 weeks, with or without topical application of silibinin (9 mg/200 µl in acetone, applied 30 min before or after UVB exposure). Results indicated that silibinin application either pre- or post-UVB exposure for 26 weeks significantly decreased the number of BCC lesions by 65% and 39% (P < 0.001 for both) and the area covered by BCCs (72% and 45%, P < 0.001 for both), respectively, compared to UVB alone. Furthermore, continuous UVB exposure for 46 weeks increased the BCC lesion number and the BCC area covered by ~6 and ~3.4 folds (P < 0.001), respectively. Notably, even in this 46 week prolonged UVB exposure, silibinin (irrespective of pre- or post-UVB treatment) significantly halted the growth of BCCs by 81-94% (P < 0.001) as well as other epidermal lesions; specifically, silibinin treated tissues had less epidermal dysplasia, fibrosarcoma, and squamous cell carcinoma. Immunohistochemistry and immunofluorescence studies revealed that silibinin significantly decreased basal cell proliferation (Ki-67) and the expression of cytokeratins (14 and 15), and Hedgehog signaling mediators Smo and Gli1 in the BCC lesions. Together, our findings demonstrate strong potential of silibinin to be efficacious in preventing the growth and progression of UVB-induced BCC., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Metformin and sulfonylureas are the most commonly prescribed drugs used for the treatment of type II diabetes. Type II diabetes has been linked to the development of keratinocyte carcinoma (KC), consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Previously we have demonstrated lower risk for a subsequent KC in metformin users. In this study, we aim to investigate the association between sulfonylureas use and the development of KC in patients with KC history. We performed a retrospective cohort study of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, which was a randomized double-blind vehicle-control cream originally investigating the effect of 5-fluorouracil on KC development. 932 patients with a history of KC were enrolled (98% male, 99% white, median age of 70 years) and followed for a median duration of 2.8 years. 153 patients were on metformin and 94 on sulfonylureas. We performed a survival analysis with cox regression and controlled for body mass index and known predictors: number of prior BCCs and age (for BCC) and for number of prior SCCs (invasive and in situ), number of actinic keratoses at baseline (for SCC). Sulfonylurea-users com-pared to non-users had a HR of 0.67 (CI: 0.40&ndash;1.56; P=0.49) and 0.94 (CI: 0.63&ndash;1.40; P= 0.77), for SCC and BCC, respectively. Diabetic patients at high risk for KC might benefit from the use of metformin versus sulfonylureas. J Drugs Dermatol. 2022;21(5):502-505. doi:10.36849/JDD.6087.

Background: Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC)., Objective: To evaluate the effect of nicotinamide in prevention of skin cancers., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of nicotinamide. We used Medline, EMBASE, CENTRAL, and Web of Science databases from their inception to October 2020 to search the following concepts: "nicotinamide"; "randomized controlled trial" (validated filters). Two independent reviewers screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. To be eligible, ≥1 outcome had to be covered. We used a standardized collection grid to complete data extraction in duplicate. The primary outcome was skin cancers (all types). Secondary outcomes were basal cell carcinomas (BCCs); cSCCs; actinic keratoses; melanomas; digestive, cutaneous, and biochemical adverse effects (AEs). Subgroup analyses were planned a priori ., Results: We screened 4730 citations and found 29 trials (3039 patients) meeting inclusion criteria. Nicotinamide was associated with a significant reduction in skin cancers compared to control (rate ratio 0.50 (95% CI, 0.29-0.85; I 2 = 64%; 552 patients; 5 trials); moderate strength of the evidence). Heterogeneity was explained by risk of bias. Nicotinamide was associated with a significant reduction in BCCs and cSCCs, and increased risk of digestive AEs., Conclusion: Oral nicotinamide should be considered in healthy patients or organ transplant recipients with history of skin cancer (GRADE: weak recommendation; moderate-quality evidence), in particular of BCC and cSCC.

Nonmelanoma skin cancer (NMSC), the most widely diagnosed cancer in the United States, is rising in incidence despite public health and educational campaigns that highlight the importance of sun avoidance. It is,therefore, important to establish other modifiable risk factors that may be contributing to this increase. There is a growing body of evidence in the literature suggesting certain nutrients may have protective or harmful effects on NMSC. We review the current literature on nutrition and its effect on NMSC with a focus on dietary fat, vitamin A, nicotinamide, folate, vitamin C, vitamin D, vitamin E, polyphenols, and selenium., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Some clinical trials found that cyclooxygenase-2 (COX-2) inhibitor use lowered the risk of skin cancer in high-risk groups., Patients and Methods: To determine whether COX-2 inhibitor use is associated with lower risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, we analyzed COX-2 inhibitor use and risk of skin cancer based on three prospective cohort studies, the Nurses' Health Study (NHS), NHS II, and the Health Professionals Follow-up Study, including 153,882 participants. Multivariable hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association of COX-2 inhibitor use with risk of BCC, cSCC, and melanoma were estimated using Cox proportional hazards models. We pooled the results using a fixed effects model., Results: 16,142 BCC, 1,973 cSCC, and 631 melanoma cases were documented. Ever vs. never use of COX-2 inhibitor was associated with a modestly increased risk of BCC (multivariable HR 1.09, 95 % CI 1.05-1.14). The hazard ratio was similar for cSCC (multivariable HR 1.12, 95 % CI 1.00-1.27) and melanoma (multivariable HR 1.10, 95 % CI 0.89-1.38), but was not statistically significant., Conclusions: Ever use of COX-2 inhibitor was not associated with a decreased skin cancer risk but was instead associated with a modest, increased risk of BCC., (© 2022 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

The rates of melanoma and non-melanoma skin cancer (NMSC) have been increasing over the last twenty years in the United States, and this has been attributed to increased ultraviolet radiation exposure (UVR). Given these rising rates, preventative measures have become increasingly important to reduce the incidence and promote early detection of these cancers. Skin cancer prevention remains a challenging task to accomplish mainly due to the lack of reliable and sensitive methods to provide objective risk information that can educate and motivate individuals to avoid sunburn. Currently, minimal erythema dose (MED) is used as a marker of UVR. However, it is not an ideal marker because significant cancer-related molecular damage can occur after UVR exposure that cannot be detected by MED. Thus, over the recent years there has been significant interest in development of biomarkers indicative of exposure to UVR to improve early detection of cutaneous malignancies. Here, we will discuss emerging biomarkers for melanoma and NMSC that can help with risk stratification and targeted prevention and treatment., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Actinic keratoses (AKs) are a common premalignant cutaneous neoplasm and can progress to squamous cell carcinoma. A variety of treatment options are available for field therapy of diffuse AKs., Objective: This review systematically analyzes the use of chemical peels for treatment of AKs., Materials and Methods: A systematic review of PubMed was performed searching from 1946 to March 2020 to identify the literature on chemical peels for AKs., Results: Of the 151 articles identified, 5 met inclusion criteria for review. Four of the reviewed articles demonstrated the efficacy of chemical peels in reducing AK count and minimal adverse effects. In some studies, chemical peels exhibited potential to prevent additional AK formation and development of keratinocyte carcinomas., Conclusion: Chemical peels are an efficacious and affordable treatment option for field treatment of AKs. With improved patient tolerance and adherence, chemical peels are an attractive option for field therapy of AKs for both dermatologists and patients., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed., Objectives: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC., Methods: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression., Results: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96)., Limitations: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities., Conclusion: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

This Perspective briefly reviews the relationship between UV-induced mutations in habitually sun-exposed human skin and subsequent development of actinic keratoses (AKs) and skin cancers. It argues that field therapy rather than AK-selective therapy is the more logical approach to cancer prevention and hypothesizes that treatment early in the process of field cancerization, even prior to the appearance of AKs, may be more effective in preventing cancer as well as more beneficial for and better tolerated by at-risk individuals. Finally, the Perspective encourages use of rapidly advancing DNA analysis techniques to quantify mutational burden in sun-damaged skin and its reduction by various therapies., (Copyright © 2021 The Author. Published by Elsevier Inc. All rights reserved.)

Background: It is unknown whether dietary supplementation with vitamin D or calcium prevents keratinocyte carcinomas, also known as nonmelanoma skin cancers., Objectives: This study aimed to determine whether daily vitamin D or calcium supplementation alters the risk of basal cell carcinoma (BCC) or invasive cutaneous squamous cell carcinoma (SCC)., Methods: The Vitamin D/Calcium Polyp Prevention Study is a completed multicenter, double-blind, placebo-controlled, partial 2 × 2 factorial, randomized clinical trial of vitamin D, calcium, or both for the prevention of colorectal adenomas. During 2004-2008, a total of 2259 men and women, 45-75 y of age, recently diagnosed with a colorectal adenoma, were randomly assigned to 1000 IU/d of vitamin D3 or placebo and 1200 mg/d of calcium carbonate or placebo for 3 or 5 y, and followed after treatment ended. Reports of incident BCC or SCC were confirmed from pathology records., Results: During a median follow-up of 8 y, 200 (9%) participants were diagnosed with BCC and 68 (3%) participants were diagnosed with SCC. BCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.96; 95% CI: 0.73, 1.26), calcium compared with no calcium (HR: 1.01; 95% CI: 0.74, 1.39), and both agents compared with neither (HR: 0.99; 95% CI: 0.65, 1.51). SCC incidence was unrelated to treatment with vitamin D compared with no vitamin D (HR: 0.79; 95% CI: 0.49, 1.27), but there was suggestive evidence of beneficial treatment effects for calcium compared with no calcium (HR: 0.60; 95% CI: 0.36, 1.01) and both agents compared with neither (HR: 0.42; 95% CI: 0.19, 0.91)., Conclusions: Calcium alone or in combination with vitamin D may reduce the risk of SCC, but not BCC. This trial was registered at clinicaltrials.gov as NCT00153816., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Society for Nutrition.)

Basal cell carcinoma (BCC) is the most prevalent malignancy, with rising incidence worldwide. Despite its naturally slow growth and initially low metastatic potential, it can cause significant morbidity and mortality when unrecognized, inadequately treated or poorly followed up. Authors present the case of a 61-year-old male with a 7-year history of multiple incomplete excisions of a &#8220;simple&#8221; BCC on the forehead. A CT scan of the head revealed an invasive mass (5.2 cm laterolateral x 4.0 cm craniocaudal) in the frontal area. There was no evidence of metastasis. Complete resection of the lesion and reconstruction was achieved in three stages. Final reconstruction was achieved using a left frontal fasciocutaneous flap. The secondary defect was closed with an advancement flap of the scalp and donor sites were covered using a split-thickness skin graft from the upper limb. This case demonstrates the necessity for vigilance in the approach to, diagnosis, treatment and follow-up of these skin neoplasms. The development of giant BCCs should be avoided at all costs. Increased size of BCCs corresponds with increased recurrence rate, metastatic rate, morbidity, mortality, treatment difficulties and overall costs.

Importance: Certain patient groups, such as solid organ transplant recipients (SOTRs), have a significantly increased risk of developing skin cancers. The chemotherapeutic drug capecitabine has been used off label as a chemopreventive modality to suppress the development of precancerous skin lesions and squamous cell carcinomas (SCCs)., Objective: To systematically review published studies on the use of capecitabine for the treatment and prevention of precancerous and cancerous skin lesions, with a focus on cutaneous SCC., Evidence Review: For this systematic review, a literature search was performed using the PubMed and Embase databases in December 2019 for all articles published between January 1, 1998, and December 31, 2019, using the search term capecitabine paired with each of the following terms: actinic keratosis, actinic keratoses, squamous cell carcinoma, and basal cell carcinoma. Articles on the use of capecitabine for the treatment and prevention of actinic keratoses (AKs), SCCs, and basal cell carcinomas (BCCs) were selected for inclusion., Findings: Sixteen publications met the criteria for inclusion, with 8 case reports describing the inflammation of AKs in patients with solid organ cancer treated with capecitabine (2 patients with breast cancer and 6 patients with colorectal cancer). One case report and 1 case series of 4 patients investigated the use of capecitabine for the treatment of advanced or widespread cutaneous SCCs. A total of 6 publications (3 case reports and 3 case series) described the use of capecitabine to prevent development of SCCs in SOTRs. Of these case series, 2 studies found a significant reduction in SCC incidence rate during treatment with capecitabine compared with before treatment. Adverse effects, such as fatigue, nausea, vomiting, diarrhea, elevated creatinine level, hand-foot syndrome, hyperuricemia, weight loss, anemia, and cardiomyopathy, limited the duration of chemoprevention in several patients., Conclusions and Relevance: Capecitabine treatment may be associated with a decrease in the incidence of SCCs in SOTRs. Capecitabine treatment may also be associated with a decrease in AK and BCC incidence. However, practitioners must weigh this benefit against the risk of adverse effects for each patient individually. Further investigation with a prospective clinical trial is warranted.

Sun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose-response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose-response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17-1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13-1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19-1.67), and 1.57 (0.64-3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH)D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk.

Background: The association of dietary pattern with the risk of basal cell carcinoma (BCC) is little understood and has scarcely been investigated., Objectives: We assessed the association of several complete dietary patterns [Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Pro-vegetarian dietary pattern] with the risk of BCC, conducting a nested case-control study (4 controls for each case)., Methods: Cases and controls were selected from the SUN (Seguimiento Universidad de Navarra) cohort using risk set sampling. Cases were identified among subjects free of skin cancer at baseline but who later reported a physician-made BCC diagnosis during the follow-up period. In the cohort we identified 101 incident cases of BCC., Results: In multivariable-adjusted conditional logistic regression analyses, better adherence to the Mediterranean diet (highest compared with lowest quintile) was associated with a 72% relative reduction in the odds of BCC (OR: 0.28; 95% CI: 0.10, 0.77; Ptrend = 0.014); the DASH diet was associated with a 68% RR reduction (OR: 0.32; 95% CI: 0.14, 0.76; Ptrend = 0.013) for the comparison between extreme quintiles. No association was found between a Pro-vegetarian dietary pattern and BCC. Higher fruit consumption (highest compared with lowest quintile, OR: 0.27; 95% CI: 0.11, 0.64; Ptrend < 0.001) and low-fat dairy products (OR: 0.39; 95% CI: 0.16, 0.92; Ptrend = 0.014) were associated with a lower BCC risk., Conclusions: Our results suggest that Mediterranean and DASH dietary patterns may be associated with a lower risk of BCC, but confirmatory studies are required., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Understanding factors that influence people to use sunscreen would allow clinicians to counsel patients in a way that is influential. Perceived efficacy of sunscreen has been associated with sunscreen use, but it is unclear whether the degree of efficacy is important., Objective: To determine whether larger perceived efficacy of sunscreen (larger skin cancer risk reduction) is associated with increased sunscreen use., Materials and Methods: A cohort of 131 patients with a history of skin cancer visiting a Mohs micrographic surgery center were surveyed., Results: Participants believed sunscreen would reduce their risk of basal cell carcinoma (BCC) by 61.1% (95% confidence interval [CI] = 56.4-65.9), squamous cell carcinoma (SCC) by 59.4% (95% CI = 54.6-64.2), and melanoma by 59.5% (95% CI = 54.8-64.3). Perceived magnitude of risk reduction of BCC, SCC, and melanoma was significant independent predictors of sunscreen use (BCC: odds ratio [OR] 3.5, 95% CI 1.1-11.2, p = .04. Squamous cell carcinoma: OR 2.8, 95% CI 1.0-7.6, p = .05. Melanoma: OR 5.0, 95% CI 1.8-14.2, p = .002)., Conclusion: Larger perceived skin cancer (BCC, SCC, and melanoma) risk reduction was associated with increased sunscreen use.

This review summarizes the evidence on the protection against skin cancer afforded by sunscreen. Solid evidence can come only from randomized controlled trials, despite a multitude of case-control and cohort studies that have addressed the issue, because observational evidence is intractably confounded since those at highest risk of skin cancer are naturally the highest users of sunscreen. Findings of the single human trial conducted in subtropical Australia during 1992-1996 with follow-up to 2014 showed that the application of a broad-spectrum, sun protection factor 16 sunscreen to exposed skin of the head and neck and upper limbs at least 3-4 days per week in adulthood can reduce the risk of developing cutaneous squamous cell carcinoma and melanoma but does not appear to reduce the risk of basal cell carcinoma (BCC) overall, although it may reduce the occurrence of multiple BCCs over time.

Non-melanoma skin cancer is the most prevalent malignancy in fair-skinned people and its incidence is increasing. Recently, studies have suggested that antihypertensive drugs may increase the risk of these tumors, particularly hydrochlorothiazide, due to its photosensitizing properties. The Portuguese National Authority for Medicines and Health Products, INFARMED, has issued an alert to healthcare professionals concerning the increased risk of non-melanoma skin cancer in patients exposed to cumulative doses of this drug. However, study results have been heterogeneous and sometimes conflicting. The high incidence of non-melanoma skin cancer and the large number of patients under chronic hydrochlorothiazide therapy may thus have important public health consequences. In this article, the authors review the published evidence and conclude that there may be an association between hydrochlorothiazide use and the risk of non-melanoma skin cancer, but also point out some limitations of the studies in the literature. It is important to promote preventive strategies against sun exposure, regular skin examinations, and individual assessment of the benefits of hydrochlorothiazide use, particularly in patients with previous skin cancer., (Copyright © 2020 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer little predictive value. However, combining multiple variants into polygenic risk scores (PRS) may be more informative. Multiple studies have developed PRS composed of GWAS-identified variants for cutaneous cancers. This review highlights data from these studies., Objectives: To review published GWAS and PRS studies for melanoma, cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), and discuss their potential clinical utility., Methods: We searched PubMed and the National Human Genome Research Institute-European Bioinformatics Institute GWAS catalogue to identify relevant studies., Results: Results from 21 GWAS (11 melanoma, 3 cSCC, 7 BCC) and 11 PRS studies are summarized. Six loci in pigmentation genes overlap between these three cancers (ASIP/RALY, IRF4, MC1R, OCA2, SLC45A2 and TYR). Additional loci overlap for cSCC/BCC and BCC/melanoma, but no other loci are shared between cSCC and melanoma. PRS for melanoma show roughly two-to-threefold increases in risk and modest improvements in risk prediction (2-7% increases). PRS are associated with twofold and threefold increases in risk of cSCC and BCC, respectively, with small improvements (2% increase) in predictive ability., Conclusions: Existing data indicate that PRS may offer small, but potentially meaningful, improvements to risk prediction. Additional research is needed to clarify the potential utility of PRS in cutaneous carcinomas. Clinical translation will require well-powered validation studies incorporating known risk factors to evaluate PRS as tools for screening. What's already known about this topic? Over 50 susceptibility loci for melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) have been identified in genome-wide association studies (GWAS). Polygenic risk scores (PRS) using variants identified from GWAS have also been developed for melanoma, BCC and cSCC, and investigated with respect to clinical risk prediction. What does this study add? This review provides an overview of GWAS findings and the potential clinical utility of PRS for melanoma, BCC and cSCC., (© 2019 British Association of Dermatologists.)

The study aimed to determine whether 25-OH vitamin D 3 deficiency is present in patients with diagnosed BCC, and the effect of vitamin D replacement on the rates of BCC recurrence in patients with 25-OH vitamin D 3 deficiency. In this prospective study, between 2012 and 2017, in the first stage, 25-OH vitamin D 3 levels of all patients diagnosed with BCC between 2012 and 2013 were evaluated. In the second stage between 2014 and 2015, we evaluated the 25-OH vitamin D 3 level of patients who had 25-OH vitamin D 3 level < 25 ng/mL. All the patients included in the second stage had BCC recurrence. In the third stage, the patients who were diagnosed 25-OH vitamin D 3 deficiency with BCC, between 2015 and 2017, were studied. The mean 25-OH vitamin D 3 level of the patients in the second stage was 10.12 ng/mL. Recurrence was observed in 9.64% of the patients in the second stage. The mean level of serum 25-OH vitamin D 3 in the third stage was 40.1 ng/mL, and 3.49% of these patients presented with recurrence. In all the patients as the initial diagnosis and following the 25-OH vitamin D 3 level in all the patients with BCC recurrence, maintaining 25-OH vitamin D 3 levels above 25 ng/mL can significantly reduce the recurrence rate.

Background: All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population-based studies on post-transplant rates of basal cell carcinoma (BCC)., Objectives: To identify trends in incidence rates for KC following solid organ transplantation over the past two decades., Methods: This nationwide, population-based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population., Results: In total 3580 solid OTRs were included. The total follow-up time was 28 407 person-years (median follow-up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994-1996 of 26·4 (21·5-32·4) and 9·1 (7·4-11·3) to 6·3 (2·3-16·7) and 3·2 (1·4-7·1) in 2012-2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades., Conclusions: Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes. What's already known about this topic? Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation. It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this. What does this study add? Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort., (© 2019 British Association of Dermatologists.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been postulated as chemopreventive agents for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but findings from observational studies have been inconsistent, and clinical trial data are scant., Objectives: To examine the association between aspirin and NSAID (nonaspirin) use and the risk of BCC and SCC in a large cohort specifically designed for skin cancer outcomes., Methods: We used data from the QSkin Study, a prospective cohort of 43 764 residents of Queensland, Australia (34 630 were included in this study and 23 581 were used in our primary analyses). We used Cox proportional hazards models to estimate the hazard ratios (HRs) between self-reported aspirin and NSAID use 1 year prior to study baseline and the first histologically confirmed BCC or SCC for high-risk (history of skin cancer excisions or more than five actinic lesions treated) and average-to-low-risk participants (no history of skin cancer excision and at most five actinic lesions treated)., Results: After a median of 3 years of follow-up, 3421 participants developed BCC and 1470 SCC (2288 BCC and 932 SCC with complete covariate information). Among the high-risk group (1826 BCC and 796 SCC), compared with never use, frequent (at least weekly) NSAID use was associated with reduced risk of BCC (HR 0·84, 95% confidence interval 0·71-0.99) but not SCC. Aspirin use was associated with reduced risk of SCC (HR 0·77, 95% confidence interval 0·64-0·93) only among infrequent (less than weekly) users and was not associated with BCC. We observed no association between NSAID or aspirin use and the risk of BCC or SCC among average-to-low-risk participants., Conclusions: While some weakly inverse associations were observed between prior use of aspirin or NSAIDs and skin cancer, the inconsistent patterns of associations do not provide convincing evidence that these medications reduce subsequent skin cancer risk. Further data on doses, duration and long-term follow-up may help us to comprehend the cumulative dose effect., (© 2019 British Association of Dermatologists.)

Chemoprevention of nonmelanoma skin cancer should be considered in patients likely to develop numerous, invasive, or metastatic nonmelanoma skin cancers. This article reviews the various topical and systemic substances studied as chemopreventive agents., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The incidence of non-melanoma skin cancer (NMSC) is dramatically increasing worldwide, despite the increased use of improved sunscreens. In 2014, the Surgeon General estimated that 2.2-5.0 million people were treated annually for NMSC. As the number of newly diagnosed skin cancers continues to rise, there is a need for additional preventative measures beyond sunscreens. Several newer topical products that focus on boosting DNA repair, modulating DNA transcription, decreasing inflammation and selectively targeting precancerous cells may play an important role in future skin cancer prevention., (© 2019 European Academy of Dermatology and Venereology.)

Background: The effectiveness of 5-fluorouracil compared with that of imiquimod for preventing keratinocyte carcinoma is unknown., Objective: To compare the effectiveness of 5-fluorouracil and that of imiquimod in preventing keratinocyte carcinoma in a real-world practice setting., Methods: We identified 5700 subjects who filled prescriptions for 5-fluorouracil or imiquimod for treatment of actinic keratosis in 2007. An intention-to-treat analysis controlling for potential confounding variables was used to calculate 2- and 5-year cumulative risk differences for subsequent keratinocyte carcinoma overall and in field-treated areas., Results: 5-Fluorouracil was associated with a statistically significant decreased risk of any keratinocyte carcinoma compared with imiquimod (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.76-0.97), but there were no significant differences in risk by tumor subtype (for squamous cell carcinoma: aHR, 0.89; 95% CI, 0.74-1.07; for basal cell carcinoma: aHR, 0.87; 95% CI, 0.74-1.03) or site-specific keratinocyte carcinoma (aHR, 0.96; 95% CI, 0.81-1.14). There were no significant differences in 2- or 5-year cumulative risk of keratinocyte carcinoma among those treated with 5-fluorouracil versus with imiquimod., Limitations: Generalizability to other practice settings may be limited., Conclusions: Whereas 5-fluorouracil was more effective in reducing keratinocyte carcinoma risk overall, we found no differences in the short- or long-term risk of subsequent site-specific keratinocyte carcinoma in a real-world practice setting., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)