Risk Of Keratinocyte Carcinoma Research Articles

The association of metformin use with keratinocyte carcinoma development in high-risk patients.

Keratinocyte carcinoma (KC) is the most common malignancy in white skinned populations. Metformin one of the most commonly prescribed drugs and has been reported to protect against solid cancers. The association between metformin and KC has not been studied in patients at high risk for a subsequent KC. The purpose of this study is to evaluate the association between metformin and KC development in high-risk patients. We performed a secondary analysis of patients enrolled in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial to compare risk for KC development between metformin users and non-users. Metformin-users compared to non-users had a significantly lower risk for squamous cell carcinoma with an adjusted Hazard ratio (HR): 0.45, (CI: 0.24-0.84, P < .01) and basal cell carcinoma (HR: 0.70, CI: 0.49-0.97, P < .03). Patients at high risk might benefit from metformin use against a subsequent KC.

Predicting which patients with actinic keratosis are at high risk of keratinocyte carcinoma (non‐melanoma skin cancer)

Predicting which patients with actinic keratosis are at high risk of keratinocyte carcinoma (non‐melanoma skin cancer)

Association Between Topical Calcineurin Inhibitor Use and Keratinocyte Carcinoma Risk Among Adults With Atopic Dermatitis

Topical calcineurin inhibitors (TCIs), primarily used to treat atopic dermatitis (AD), carry a black box label warning users about the potential for increased skin cancer risk. The risk associated with keratinocyte carcinoma (KC), the most common cancer, defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), remains poorly defined because findings from large-scale postmarketing surveillance studies have not been reported. To examine KC risk overall and by subtype (BCC and SCC) among adults with AD exposed to TCIs compared with those exposed to topical corticosteroids (primary comparator group) and those unexposed to TCIs or topical corticosteroids (alternative comparator group) as well as alterations in risk with TCI dose, frequency, and duration of exposure. A retrospective cohort study was conducted at Kaiser Permanente Northern California, a large, integrated health care delivery system, of adults 40 years or older (n = 93 746) with a physician-rendered diagnosis of AD or dermatitis. Patients who were diagnosed from January 1, 2002, to December 31, 2013, were included, with follow-up through December 31, 2017. Data analysis was conducted from June 1, 2016, to October 1, 2018. Time-varying pharmacy-dispensed TCI exposure (n = 7033) over the study period was compared with topical corticosteroids (n = 73 674) and no TCI or topical corticosteroid exposure (n = 46 141). Electronic pathologic testing-validated incident KCs (n = 7744). Among a cohort of 93 746 members, the mean (SD) age was 58.5 (12.7) years, and 55 023 patients (58.7%) were women. Multivariable Cox proportional hazards regression revealed no association between TCI exposure and KC risk (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.93-1.13) compared with topical corticosteroid exposure. Similarly, there were no significant differences in BCC risk (aHR, 1.01; 95% CI, 0.90-1.14, TCI vs topical corticosteroids) or SCC risk (aHR, 0.94; 95% CI, 0.82-1.08, TCI vs topical corticosteroids). Changing the comparator group to unexposed individuals yielded similar findings (aHR, 1.04; 95% CI, 0.91-1.19, TCI vs unexposed for basal cell carcinoma). There were no associations between TCI dose, frequency, and duration of use and BCC, SCC, or overall KC risk. The results of this postmarketing surveillance study of adult health plan members with AD revealed no apparent association between TCI exposure and overall KC, BCC, or SCC risk. Secondary analyses examining dose, frequency, and duration of TCI exposure revealed no associations. These findings suggest that use of TCIs may be safe with respect to KC risk among adults with AD.

429 Risk of keratinocyte carcinoma among patients with hidradenitis suppurativa

Recent studies have implicated the role of the Notch pathway in keratinocyte carcinomas (KCs). Notch signaling is often upregulated in basal cell carcinoma (BCC) but downregulated in squamous cell carcinoma (SCC). Hidradenitis suppurativa (HS) is an inflammatory disorder of the apocrine glands whose pathogenesis has also been associated with downregulation of Notch signaling. Given the role of Notch in the pathogenesis of HS and KCs, we hypothesized that HS patients could be at decreased risk for BCC and increased risk for SCC. To test our hypothesis, we examined the association between HS and KC risk by comparing the incidence of BCC and SCC in HS patients to controls (patients with acne vulgaris, an inflammatory disorder of pilosebaceous glands that is not known to involve the Notch pathway). Using an age, sex, and race matched 1:2 case-control study design, we derived KC outcomes and covariates through chart review of an institutional database (Partners Healthcare, 2000-2019) and determined incident BCC and SCC risk by performing multivariate logistic regression adjusted for disease duration, BMI, smoking, immunosuppression, and number of dermatology visits. The study population consisted of 13,812 patients (4,604 HS and 9,208 acne patients), of which 59% were white, 74.7% female, and mean (SD) age was 43.7 (15.4) years. Adjusted odds ratio (OR) for incident BCC risk in HS was OR 0.51 (95% CI 0.37-0.71, P<0.001) whereas adjusted OR for incident SCC risk was 0.79 (95% CI 0.54-1.17, P=0.238). There were no statistical differences in age, gender, and race among those who developed BCC or SCC between groups (all P>0.05). Our results suggest that HS patients have reduced risk of BCC, and similar risk of SCC, compared with controls (acne patients). Further studies are needed to investigate whether decreased Notch signaling in HS patients plays a protective role in BCC tumorigenesis or whether inflammation of the pilosebaceous unit in acne affects follicular bulge cells to increase risk of BCCs.

Skin cancer risk and shade: comparing the risk of foresters with other outdoor workers.

Keratinocyte carcinoma (KC) is an increasingly important public health problem with an especially high prevalence in outdoor workers. In contrast to other occupations, foresters spend most of their outdoor time under the shade of trees. We aimed to compare the unique sun exposure patterns and sun protection behaviour of foresters with those of other outdoor workers and their relation to the KC risk. In July 2018, a cross-sectional study was conducted at an international forestry fair using a questionnaire about health awareness and skin cancer screening by dermatologists to assess the prevalence of KC. A total of 591 participants (78.7% male; mean age 46.8±16.2years) including 193 foresters were enrolled. Of all foresters, 72% experienced sunburns (solar erythema) within the past year and 50% of them experienced the worst sunburn during work. Foresters were most likely to often/always wear protective clothes (29.0%) but were least likely to often/always avoid midday sun (23.8%) and stay in the shade (31.1%). Having an outdoor profession or spending hours outside for leisure was negatively associated with sun protection. Skin examination revealed an overall KC prevalence of 16.7%, with 16.5% of foresters being affected. Despite being protected by trees, the risk of KC for foresters is comparable to that of other professional groups. Shade alone may not provide sufficient protection. Additional sun protection measures are necessary.

Genetic and environmental factors underlying keratinocyte carcinoma risk.

Recent large-scale GWAS and large epidemiologic studies have accelerated the discovery of genes and environmental factors that contribute to the risk of keratinocyte carcinoma (KC), which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This Review summarizes the genomic regions associated with SCC and BCC risk, examines the genetic overlap between SCC and BCC, and discusses biological pathways involved in SCC and BCC development. Next, we review environmental factors that are associated with KC risk, including those that are shared between SCC and BCC as well as others that associated with only one type of KC. We conclude with a critical appraisal of current research and potential directions for future research.

Voriconazole and the Risk of Keratinocyte Carcinomas Among Lung Transplant Recipients in the United States

The antifungal medication voriconazole is used to prevent and treat aspergillosis, a major cause of mortality among recipients of lung transplants (hereinafter referred to as lung recipients). Small studies suggest that voriconazole increases risk of cutaneous squamous cell carcinoma (SCC). To examine associations of voriconazole and other antifungal medications with risk of keratinocyte carcinomas (SCC and cutaneous basal cell carcinoma [BCC]) in lung recipients. This population-based cohort study included non-Hispanic white patients (n = 9599) who underwent lung transplant in the United States from January 1, 2007, to December 31, 2016, identified through the national Scientific Registry of Transplant Recipients with data linkable to pharmacy claims. Data were analyzed from March 1, 2018, to February 13, 2019. Antifungal medication use, including voriconazole, itraconazole, posaconazole, and other antifungals, was ascertained from pharmacy claims and treated as a time-varying exposure (assessed every 30 days). Cumulative antifungal exposure was calculated as the total number of exposed months. Primary outcomes were the first SCC or BCC reported to the transplant registry by transplant centers. Follow-up began at transplant and ended at SCC or BCC diagnosis, transplant failure or retransplant, death, loss to follow-up, or December 31, 2016. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) for each antifungal medication. Among the 9793 lung transplants in 9599 recipients included in the analysis, median age at transplant was 59 (interquartile range [IQR], 48-65) years, 5824 (59.5%) were male, and 5721 (58.4%) reported ever smoking. During a median follow-up of 3.0 (IQR, 1.4-5.0) years after transplant, 1031 SCCs (incidence, 322 per 10 000 person-years) and 347 BCCs (incidence, 101 per 10 000 person-years) were reported. Compared with lung recipients with no observed voriconazole use, those with 1 to 3 months of voriconazole use experienced increased AHR for SCC of 1.09 (95% CI, 0.90-1.31); 4 to 7 months, 1.42 (95% CI, 1.16-1.73); 8 to 15 months, 2.04 (95% CI, 1.67-2.50); and more than 15 months, 3.05 (95% CI, 2.37-3.91). Ever itraconazole exposure was associated with increased SCC risk (AHR, 1.20; 95% CI, 1.00-1.45). For BCC, risk was not associated with voriconazole use but was increased with itraconazole use (AHR, 1.74; 95% CI, 1.27-2.37) or posaconazole use (AHR, 1.55; 95% CI, 1.00-2.41). In this study, voriconazole use was associated with increased SCC risk among lung recipients, especially after prolonged exposure. Further research evaluating the risk-benefit ratio of shorter courses or alternative medications in transplant recipients at high risk for SCC should be considered.

Risk Factors for Keratinocyte Carcinoma in Recipients of Allogeneic Hematopoietic Cell Transplants

Allogeneic hematopoietic cell transplant (alloHCT) is known to increase the risk for keratinocyte carcinoma. The extent to which host characteristics, including pigmentary phenotype and UV radiation exposure, contribute is unknown. To identify and validate independent risk factors for keratinocyte carcinoma after alloHCT, including those associated with the transplant and the host. This retrospective cohort study analyzed a consecutive sample of alloHCT recipients from January 1, 2000, to December 31, 2014, at the Mayo Clinic, Rochester, Minnesota (n = 872) and University Hospitals Cleveland Medical Center, Cleveland, Ohio (n = 147). Participants from the Mayo Clinic were randomly allocated (2:1) into discovery (n = 581) and validation (n = 291) cohorts. Time to first keratinocyte carcinoma and information about transplant- and host-associated risk factors were extracted. A multivariate keratinocyte carcinoma risk model was created using a stepwise Cox proportional hazards regression model with P ≤ .05 for entry that incorporated all covariates that were individually statistically significant at α = 0.05 in the discovery cohort. The risk model was first internally validated using the Mayo Clinic validation cohort and then externally validated using the independent cohort of alloHCT recipients at University Hospitals Cleveland Medical Center. Data were analyzed from March 13, 2018, to June 12, 2019. Allogeneic hematopoietic cell transplant. The primary outcome was time to development of the first cutaneous keratinocyte carcinoma after alloHCT; secondary outcome, time to development of the first individual basal and/or squamous cell carcinoma after alloHCT. Of the 872 alloHCT recipients identified in the Mayo Clinic cohort (520 men [59.6%]; mean [SD] age, 48.3 [12.6] years), 95 (10.9%) developed keratinocyte carcinoma after alloHCT during 5349 person-years of follow-up. Of the 147 alloHCT recipients in the exernal validation cohort (86 men [58.5%]; mean [SD] age, 47.9 [17.5] years), 18 (12.2%) developed keratinocyte carcinoma after alloHCT in 880 person-years of follow up. Risk factors independently associated with keratinocyte carcinoma after alloHCT included age (hazard ratio [HR] per 10 years, 1.72; 95% CI, 1.21-2.42), chronic lymphocytic leukemia (HR, 2.47; 95% CI, 1.20-5.09), clinically photodamaged skin (HR, 3.47; 95% CI, 1.87-6.41), and history of cutaneous squamous cell carcinoma (HR, 2.60; 95% CI, 1.41-5.91). Harrell concordance statistics were 0.81 (95% CI, 0.72-0.90) and 0.86 (95% CI, 0.74-0.98) for internal and external validation of the keratinocyte carcinoma risk model, respectively. This study found validated independent risk factors for keratinocyte carcinoma after alloHCT that are enriched with host- compared with transplant-associated risk factors. These findings highlight the importance of assessing host-associated risk factors for keratinocyte carcinoma in patients eligible for alloHCT. Future studies should examine whether keratinocyte carcinoma risk stratification before alloHCT may inform long-term surveillance strategies.

Predicting keratinocyte carcinoma in patients with actinic keratosis: development and internal validation of a multivariable risk-prediction model.

SummaryBackgroundPatients with actinic keratosis (AK) are at increased risk for developing keratinocyte carcinoma (KC) but predictive factors and their risk rates are unknown.ObjectivesTo develop and internally validate a prediction model to calculate the absolute risk of a first KC in patients with AK.MethodsThe risk‐prediction model was based on the prospective population‐based Rotterdam Study cohort. We hereto analysed the data of participants with at least one AK lesion at cohort baseline using a multivariable Cox proportional hazards model and included 13 a priori defined candidate predictor variables considering phenotypic, genetic and lifestyle risk factors. KCs were identified by linkage of the data with the Dutch Pathology Registry.ResultsOf the 1169 AK participants at baseline, 176 (15·1%) developed a KC after a median follow‐up of 1·8 years. The final model with significant predictors was obtained after backward stepwise selection and comprised the presence of four to nine AKs [hazard ratio (HR) 1·68, 95% confidence interval (CI) 1·17–2·42], 10 or more AKs (HR 2·44, 95% CI 1·65–3·61), AK localization on the upper extremities (HR 0·75, 95% CI 0·52–1·08) or elsewhere except the head (HR 1·40, 95% CI 0·98–2·01) and coffee consumption (HR 0·92, 95% CI 0·84–1·01). Evaluation of the discriminative ability of the model showed a bootstrap validated concordance index (c‐index) of 0·60.ConclusionsWe showed that the risk of KC in patients with AK can be calculated with the use of four easily assessable predictor variables. Given the c‐index, extension of the model with additional, currently unknown predictor variables is desirable. Linked Comment: Kim et al. Br J Dermatol 2020; 183:415–416.

Viruses in Skin Cancer (VIRUSCAN): Study Design and Baseline Characteristics of a Prospective Clinic-Based Cohort Study.

Accumulating evidence suggests that cutaneous viral infections are risk factors for the development of keratinocyte carcinomas. The Viruses in Skin Cancer (VIRUSCAN) Study, a prospective cohort study, was established in 2014 to investigate the risk of keratinocyte carcinoma associated with cutaneous human papillomavirus and polyomavirus infection and the possible interaction with ultraviolet radiation exposure (UVR). VIRUSCAN incorporates repeated measures of viral infection using multiple markers of infection and quantitative measures of UVR using a spectrophotometer. Participants were recruited between July 14, 2014 and August 31, 2017 at the University of South Florida Dermatology Clinic in Tampa, FL. After excluding 124 individuals with prevalent keratinocyte carcinomas at baseline, 1,179 participants (53.2% women, 46.8% men, all ages 60 years and older) were followed for up to 4 years with routine skin exams occurring every 6 to 12 months. Here, we present the VIRUSCAN Study design, methods, and baseline characteristics, including demographics, sun exposure behavior, quantitative UVR exposure measurements, and cutaneous viral prevalence, for the full study cohort. The VIRUSCAN Study will provide critical temporal evidence needed to assess the causality of the role cutaneous viral infections play in the development of keratinocyte carcinomas, as well as the potential interaction between cutaneous viral infections and UVR exposure. Study findings will be valuable in future development of novel keratinocyte carcinoma prevention strategies.

Noncutaneous and Cutaneous Cancer Risk in Patients With Atopic Dermatitis

Impaired skin barrier and aberrant immune function in atopic dermatitis (AD) may alter immune response to malignant cancer. Conflicting data exist on the risk of cancer in patients with AD. To assess the risk of noncutaneous and cutaneous cancers in patients with AD compared with the general population without AD. Studies identified from searches of MEDLINE and Embase that were published from 1946 and 1980, respectively, to January 3, 2019. The following search terms were used: [(exp NEOPLASMS/ OR neoplas*.tw. OR tumo*.tw. OR cancer*.tw. OR malignanc*.tw.) AND (exp Dermatitis, Atopic/ OR (atopic adj1 (dermatit* or neurodermatit*)).tw. OR eczema.tw. OR disseminated OR neurodermatit*.tw.)]. Included were observational studies (cohort and case-control designs) reporting a risk estimate for cancer in patients with AD compared with a control group (general population or patients without AD). Two independent reviewers extracted data and assessed the risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool, modified for observational exposure studies. Data were pooled using a random-effects model and expressed as standardized incidence ratios (SIRs) or odds ratios (ORs) with 95% CIs. Heterogeneity was assessed using the Cochrane Q statistic and the I2 statistic. The main outcome of the study was risk of cancer measured by SIRs or ORs. This systematic review and meta-analysis included 8 population-based cohort studies (n = 5 726 692 participants) and 48 case-control studies (n = 114 136 participants). Among cohort studies, a statistically significant association was found between AD and keratinocyte carcinoma (5 studies; pooled SIR, 1.46; 95% CI, 1.20-1.77) as well as cancers of the kidney (2 studies; pooled SIR, 1.86; 95% CI, 1.14-3.04), central nervous system (2 studies; pooled SIR, 1.81; 95% CI, 1.22-2.70), and pancreas (1 study; SIR, 1.90; 95% CI, 1.03-3.50). Among 48 case-control studies, pooled effects showed patients with AD had statistically significantly lower odds of central nervous system cancers (15 studies; pooled OR, 0.76; 95% CI, 0.70-0.82) and pancreatic cancer (5 studies; pooled OR, 0.81; 95% CI, 0.66-0.98), contrary to the higher incidence found in cohort studies. Case-control studies also demonstrated lower odds of lung and respiratory system cancers (4 studies; pooled OR, 0.61; 95% CI, 0.45-0.82). No evidence of association was found between AD and other cancer types, including melanoma. There was substantial heterogeneity between studies for many other cancers, which precluded pooling of data, and there was moderate to serious risk of bias among included studies. Observational evidence suggests potential associations between AD and increased risk of keratinocyte carcinoma and kidney cancer as well as lower odds of lung and respiratory system cancers. Further research is needed to address the heterogeneity and limitations of current evidence and to better understand the mechanisms underlying a possible association between AD and cancer risk.

Declining incidence of keratinocyte carcinoma in organ transplant recipients.

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). To identify trends in incidence rates for KC following solid organ transplantation over the past two decades. 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. In total 3580 solid OTRs were included. The total follow-up time was 28407 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. 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.

Association between Human Leukocyte Antigen Type and Keratinocyte Carcinoma Risk in Renal Transplant Recipients

Keratinocyte carcinoma (KC), defined as squamous cell carcinoma and basal cell carcinoma, is the most common malignancy among white, non-Hispanic renal transplant recipients. Although recent genome-wide association studies reported that class II HLA is associated with KC risk, epidemiologic data on HLA type and KC risk in renal transplant recipients is limited. Using an institutional cohort of white, non-Hispanic renal transplant recipients transplanted between 1993 and 2017, we examined the association between pretransplant molecular HLA types and KC risk. Posttransplant KCs were captured using the International Classification of Diseases codes and validated using pathology reports. Cox proportional hazards regression models were used to estimate hazard ratios of incident KC, squamous cell carcinoma, and basal cell carcinoma, adjusting for age, male sex, history of KC, Charlson comorbidity index, HLA mismatch, transplant type, year of transplant, and the type of immunosuppression. Among 617 subjects (mean age 53 years, 67% male), 10% developed posttransplant KC. Multivariable Cox regression analyses showed HLA-DRB1∗13 was associated with KC risk (hazard ratio, 1.84; 95% confidence interval, 1.00-3.38) and squamous cell carcinoma risk (hazard ratio, 2.24; 95% confidence interval, 1.12-4.49), whereas HLA-DRB1∗14 (hazard ratio, 2.81; 95% confidence interval, 1.14-6.91) was associated with basal cell carcinoma risk. Our findings suggest that a subset of renal transplant recipients with specific HLA polymorphisms may be at increased KC risk.

Effects of increased actinic keratosis count on skin-related quality of life: results from the Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial.

Actinic keratoses (AKs) are very common and it is therefore important to consider how morbidity of this disease impacts quality of life (QoL). Previous longitudinal studies of skin-related QoL in a high-risk population found no effect of increased AK counts on subsequent skin-related QoL, even though higher AK counts were associated with worse skin-related QoL cross-sectionally. To determine if development of new actinic keratoses (AKs) are associated with worse skin-related QoL in those at high risk of keratinocyte carcinoma (KC). A prospective analysis was performed using data from the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, a randomized, double-blinded, placebo-controlled trial of topical 5-fluorouracil for chemoprevention of KC. We report correlates of skin-related quality of life, a secondary outcome of the trial. Demographic and health-related information were self-reported and AK multiplicity on the face/ears were noted on semi-annual skin exams. Skindex-29 and Skin Cancer Index instruments were used to assess skin-related QoL yearly. Participants with increased AK counts had worse skin-related QoL compared to those with unchanged or decreased counts, particularly in Year 1. Our findings of impaired skin-related QoL associated with AKs underscore the importance of appropriate management to reduce the burden of disease.

Level of UV Exposure, Skin Type, and Age Are More Important than Thiopurine Use for Keratinocyte Carcinoma Development in IBD Patients.

Retrospective studies observe an increased risk of keratinocyte carcinomas (KCs) in patients with inflammatory bowel disease (IBD) on thiopurine (TP) medication. The role of traditional risk factors such as skin type and sun protection behavior has not been studied in this population. This study aimed to examine traditional KC risk factors and thiopurine use on skin cancer development in an IBD cohort. Consecutive IBD patients were recruited from four specialist centers in Australia and New Zealand, each with varying UV exposure indices. Data pertaining to race, skin color, freckling and sun protection behavior, dose of TP therapy, and skin cancer development were elicited through a self-reported questionnaire. A total of 691 IBD patients were included with 62 reporting KC development. Thiopurine usage was similar among patients who developed skin cancer compared with those who did not (92% vs. 89%, p = 0.3). There was no statistically significant association between KC development and TP dose or 6-thioguanine nucleotide levels. In multivariate modeling, four factors were independently and significantly associated with KC: age over 61years old versus less than 30years old (OR 6.76; 95% CI 2.38-19.18), residing in Brisbane versus Christchurch (OR 3.3; 95% CI 1.6-6.8), never staying in the shade versus staying in the shade ≥ 50% of the time (OR 3.8; 95% CI 1.4-10.5), and having a skin type that never tanned versus other skin types (OR 6.9; 95% CI 2.9-16.0). Skin type, age, and sun protection behavior are more important risk factors for KC development than thiopurine medication use in this IBD population.

255 Prospective evaluation of body mass index, sun-protective behavior and keratinocyte carcinoma risk

255 Prospective evaluation of body mass index, sun-protective behavior and keratinocyte carcinoma risk

270 Development and validation of a simple model to predict the risk of keratinocyte carcinoma on screening total body skin examination

Keratinocyte carcinoma (KC) is the most common cancer in the U.S., and diagnostic delay is associated with increased morbidity and treatment costs. Although data suggests screening total body skin examination (TBSE) detects incidental skin cancers, there are no guidelines for providers to triage patients to TBSE. Prior predictive models of KC risk are cumbersome to implement clinically. We sought to develop a simple model to predict the risk of KC on TBSE. We used data from a previously published prospective, multicenter international prospective study that examined rates of skin cancer detection via TBSE in patients who presented to dermatology clinic for unrelated focused chief complaints. Multivariable analysis identified age, prior history of KC, and skin phototype as significant risk factors. These risk factors were incorporated into a points system that exhibited a ROC curve with high discrimination (c-statistic 0.82). The model was then validated in an American cohort of patients; those with a positive score were 10-fold more likely to have KC on TBSE (p < 0.001). We propose the acronym CAP (cancer history, age, phototype) as a simple mnemonic for this model which may be used clinically to increase the yield of TBSE by dermatologists in diagnosing KC and guide primary care referrls for TBSE for KC detection.

Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies.

Exposure to environmental trace elements has been studied in relation to many cancers. However, an association between exposure to trace elements and skin cancer remains less understood. Therefore, we conducted a systematic review of published epidemiologic literature examining the association between exposure to trace elements, and risk of melanoma and keratinocyte carcinoma in humans. We identified epidemiologic studies investigating exposure to arsenic, cadmium, chromium, copper, iron, selenium, and zinc and risk of skin cancer in humans. Among the minerals, arsenic, selenium, and zinc had more than five studies available. Exposure to arsenic was associated with increased risk of keratinocyte carcinoma, while too few studies existed on melanoma to draw conclusions. Exposure to selenium was associated with possible increased risk of keratinocyte carcinoma. Studies of zinc and skin cancer were case-control in design and were found to have inconsistent associations. The data on the association between cadmium, chromium, copper, and iron and risk of skin cancer remain too sparse to draw any conclusions. In summary, epidemiologic studies on exposure to trace elements and cutaneous malignancies are limited. Studies with larger sample sizes and prospective designs are warranted to improve our knowledge of trace elements and skin cancer.

Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: A cohort study

The effectiveness of 5-fluorouracil compared with that of imiquimod for preventing keratinocyte carcinoma is unknown. To compare the effectiveness of 5-fluorouracil and that of imiquimod in preventing keratinocyte carcinoma in a real-world practice setting. 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. 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. Generalizability to other practice settings may be limited. 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.

Risk of keratinocyte carcinoma following field treatment of actinic keratoses with 5-fluorouracil versus imiquimod

Risk of keratinocyte carcinoma following field treatment of actinic keratoses with 5-fluorouracil versus imiquimod