Risk Of Non-melanoma Skin Cancer Research Articles

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Associations of thiazide use with skin cancers: a systematic review and meta-analysis

BackgroundPrevious findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides.MethodsWe searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analysed separately. A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use.ResultsWe included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.16, 95% CI 1.08–1.24; HR 1.26, 95% CI 1.04–1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06–1.65; HR 1.61, 95% CI 0.97–2.67), and melanoma (OR 1.11, 95% CI 1.02–1.20; HR 1.03, 95% CI 0.93–1.14). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43–4.57; HR 1.20, 95% CI 1.00–1.45). Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05–1.33), nodular (OR 1.23, 95% CI 1.08–1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08–1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. However, the associations of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide.ConclusionsHydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions.Trial registrationPROSPERO CRD42021234317.

Sun Exposure Makes no Discrimination based on Vitamin D Status and VDR-Foki Polymorphisms for Non-Melanoma Skin Cancers Risk in Iranian Subjects: A Case-Control Study.

Background and Objective:Sunlight exposure, the main source of endogenous vitamin D synthesis, may increase the risk of non-melanoma skin cancers (NMSC) development. Vitamin D receptor (VDR) polymorphisms are associated with various malignancies. This study aimed to examine the associations between vitamin D status and VDR FokI polymorphisms in Iranian subjects with NMSC. Materials and Methods:This case-control study included 73 diagnosed cases of NMSC and 72 healthy controls from dermatology clinics at Razi Hospital, Tehran, Iran. A questionnaire was used to assess sunlight exposure. The extracted DNA from whole blood samples was genotyped and serum concentrations of 25-hydroxycalciferol (25(OH)D)) and intact parathyroid hormone (iPTH) were measured. Results:We found a significant higher duration of cumulative sunlight exposure in cases compared with controls (p<0.001). However, 25(OH)D and iPTH concentrations were not significantly different between cases and controls (30±15 vs. 29±15 ng/mL, p=0.78 and 46.0±20 vs. 40.5±23 pg/mL, p=0.14, respectively). We did not observe any significant increased risk of NMSC due to f allele, as compared with FF (OR =2.33, 95% CI 0.81-6.75, p=0.12). Conclusion:Though sunlight exposure was associated with increased NMSC risk, there were no significant associations between vitamin D status or VDR FokI polymorphisms with NMSC development in our subjects.

INDIVIDUAL ANTIHYPERTENSIVE MEDICATION AND SKIN CANCER RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its enninnsitising properties, but photosensitivity has also been reported for other antihypertensive drugs. We conducted a systematic review and meta-analysis to compare skin cancer risk among antihypertensive drug classes and between individual blood pressure lowering drugs. Design and method: We searched Medline, Embase and the Web of Science and included studies that investigated the association between antihypertensive medication exposure and non-melanoma skin cancer (NMSC) or cutaneous malignant melanoma (CMM). We combined the extracted the adjusted odds ratios (OR) using a random effects model. We performed sensitivity analyses comparing study type, population and studies with and without correction for important covariates. Results: We included 37 studies. Diuretics (n = 16,625,573), in particular hydrochlorothiazide (n = 16,068,501), and calcium channel blockers (CCB, n = 13,176,689) were examined more frequently than beta-blockers (n = 94,872) or ennin-angiotensin system inhibitors (n = 2,014,579). Exposure to diuretics (OR 1.33, 95% CI [1.10–1.61]) and CCB (OR 1.06, 95% CI [1.04–1.09]) was associated with an increased risk for NMSC. No antihypertensive drug class was associated with an increased risk for CMM. Within every drug class, at least 1 individual drug was associated with an increased risk for NMSC: nifedipine, hydrochlorothiazide, sotalol, verapamil, enalapril and bendroflumethiazide. Increased NMSC risk was only observed in case-control studies, specific populations (such as non-Hispanic whites, patients with coronary heart disease or veterans) and studies that did not correct for important covariates. No increased NMSC risk was observed in cohort studies, the general population, and studies that did correct for the covariates sun exposure, skin phototype or smoking (Figure). Only 2 out of 37 studies provided information about antihypertensive co-medication. Egger's test revealed a significant publication bias for the subgroup of diuretics and hydrochlorothiazide concerning NMSC (both p &lt; 0.0001). Conclusions: Of all antihypertensive drugs, diuretics and calcium channel blockers may be associated with an increased risk of NMSC, but causal inferences remain difficult to make because of substantiation limitation of the available data.

Most commonly prescribed blood pressure lowering drug linked with increased risk of skin cancer.

To the Editor, Hydrochlorothiazide (HCTZ) is the most commonly prescribed antihypertensive drug that belongs to a diuretic class.1 It mainly works by increasing the removal of excess water and salts from the body into the urine and by this function it is most widely used alone or in combination with other medications to treat patients with uncontrolled blood pressure and edema that results from numerous medical conditions like heart, Liver and kidney diseases. It also helps treat other ailments like diabetes insipidus, renal tubular acidosis and reduce the risk of kidney stones in patients with high calcium levels in urine. Despite its various uses and benefits, HCTZ comes with a heavy price of undesirable side effects like fatigue, lethargy, gastrointestinal discomfort and is known to cause hyperuricemia and hypokalemia associated with increased blood glucose.2 Furthermore, HCTZ increases the skin sensitivity to sunlight. However, recent research has revealed a more worrisome side effect of HCTZ that needs to be highlighted. In 2017, a nationwide study conducted in Denmark involving more than 70,000 patients with Basal cell carcinoma and 8000 patients with squamous cell carcinoma found a considerably increased risk of developing Non melanoma skin cancer, particularly among the users of HCTZ.3 A recent study also substantiated that a total of 135 squamous cell carcinoma events per 100,000 person years were reported in new users of HCTZ.4 These alarming figures raise a question mark on the safety of HCTZ use. Moreover, HCTZ is now classified as a carcinogenic agent for humans by the International Agency for Research on Cancer and the U.S. Food and Drug Administration has also permitted changes to the HCTZ drug label to warn the health care workers and patients of the risk of non-melanoma skin cancer. 5, 6 Unfortunately in Pakistan, HCTZ is still heavily used as a diuretic and people are not much aware of this new fact. In view of these findings and the fact that HCTZ is among the most generally prescribed drugs in Pakistan, its potential indication of causing skin cancer would impose a serious public health concern so the responsibility lies on the cardiologists, nephrologists and other medical physicians to be aware of this possible hazardous outcome of HCTZ use and should be cautious while prescribing it to patients who are at risk of developing skin cancer or who have had a history of skin cancer.

Atopic Dermatitis and Skin Cancer Risk: A Systematic Review.

IntroductionAtopic dermatitis (AD) is one of the most common skin diseases, and it may be associated with skin cancer risk. However, there is a controversy pertaining to whether it implies a greater or decreased risk of skin cancers. We aimed to study the relationship between AD and skin cancer risk.MethodsPubMed and Embase databases from their inception to 4 August 2021 were systematically searched.ResultsWe evaluated 16 studies involving a total of 9,638,093 participants examining the contribution of AD to skin cancers. Random-effects model was applied to estimate the overall effect sizes. The pooled analysis of 16 studies indicated that AD was significantly associated with an overall increased risk of skin cancer. Subgroup pooled analyses showed that AD was statistically associated with an increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). With regard to cohort study, AD was statistically associated with an increased risk of nonmelanoma skin cancer (NMSC), BCC, and SCC, but not melanoma risk. Sensitivity analysis revealed that excluding each study in turn did not alter the overall combined results. No publication bias existed among the studies.ConclusionIt can be concluded that AD is associated with risk of skin cancers; however, this association still needs to be verified in well-designed, worldwide trials (especially prospective, non-Western studies). The mechanism of AD leading to skin cancer is not clear, and further research is needed to explore the possibility of a potential pathogenesis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00720-2.

Risk factors for non-melanoma skin cancer development in renal transplant recipients: a 40-year retrospective study in Croatia

AimTo determine the prevalence of non-melanoma skin cancer (NMSC) and disease-specific risk factors in renal transplant recipients (RTRs).MethodsThis retrospective cohort study enrolled 1232 RTRs (736 men) treated in University Hospital Center Zagreb over 40 years. The effect of sex, age at transplantation, geographic residence, dialysis vintage, and the type of immunosuppressive therapy on NMSC occurrence was investigated.ResultsThe prevalence of NMSC was 6.81%. Overall, 60.7% of patients developed basal cell carcinoma (BCC) and 30.9% of patients developed cutaneous squamous cell carcinoma (cSCC). Only 8.3% developed both tumors. The BCC:cSCC ratio was 1.76:1. The risk for NMSC was 50% higher in men. Patients older than 50 years at transplantation were at greater risk for NMSC development. Residence in an area with higher ultraviolet exposure and dialysis vintage before transplantation did not influence NMSC development. Cyclosporine and azathioprine treatment conferred a greater risk for NMSC than tacrolimus or mycophenolate mofetil treatment.ConclusionRTRs are at high risk for NMSC development. Sex, age at transplantation, and type of immunosuppressive therapy play a role in tumor development.

Stimulating Sunscreen Use Among Outdoor Construction Workers: A Pilot Study.

BackgroundOutdoor workers (OW) receive a higher dose of ultraviolet radiation (UVR) compared to indoor workers (IW) which increases the risk of non-melanoma skin cancer (NMSC). Regular sunscreen use reduces the NMSC risk, however, adequate sun-safety behavior among OW is poor. The main objective was to conduct method- and intervention-related elements of a future intervention trial among OW, based on providing sunscreen and assessing sunscreen use on group- and individual level.MethodsThis pilot study was conducted at a construction site in the Netherlands from May-August 2021. Nine dispensers with sunscreen (SPF 50+) were installed at the worksite. OW (n = 67) were invited to complete two (cross-sectional) questionnaires on sun-safety behavior, before and after providing sunscreen. Stratum corneum (SC) samples for the assessment of UV-biomarkers were collected from the forehead and behind the ear from 15 OW and 15 IW. The feasibility of the following elements was investigated: recruitment, (loss to) follow-up, outcome measures, data collection, and acceptability of the intervention.ResultsThe first questionnaire was completed by 27 OW, the second by 17 OW. More than 75 percent of the OW were aware of the risks of sun exposure, and 63% (n = 17) found sunscreen use during worktime important. The proportion of OW never applying sunscreen in the past month was 44.4% (n = 12) before, and 35.3% (n = 6) after providing sunscreen. A majority of OW (59.3%, n = 16) found sunscreen provision encouraging for sunscreen use, the dispensers easy to use (64.7%, n = 17) and placed in practical spots (58.8%, n = 18). Collecting SC-samples was fast and easy, and several UV-biomarkers showed higher levels for sun-exposed compared to less exposed body parts. There was no significant difference in UV-biomarker levels between OW and IW.ConclusionsThis pilot study revealed low sunscreen use among OW despite providing sunscreen, overall satisfaction with the sunscreen, and the sufficient awareness of the risks of UVR-exposure. Collecting SC-samples at the workplace is feasible and several UV-biomarkers showed to be promising in assessing UVR-exposure. The low participation rate and high loss to follow-up poses a challenge for future intervention studies.

Malignant and in situ subtypes of melanoma are associated with basal and squamous cell carcinoma and its precancerous lesions

Patients with cutaneous malignant melanoma (CMM) are at increased risk of non-melanoma skin cancers (NMSCs) and possibly precancerous lesions. To analyse the association between CMM and not only NMSCs but also precursor lesions, actinic keratosis (AK) and Bowen disease (BD). The Finnish Cancer Registry data was used to calculate the age-standardized incidence ratio during 2000-2013 for basal (BCC) and squamous (SCC) cell carcinoma in patients with CMM. All tissue material collected from 70,420 subjects during 2000-2013 and reposited in the Biobank of Eastern Finland was used to calculate the age-standardized prevalence of BCC, SCC, BD and AK in CMM patients. In both genders, the age-standardized incidence ratio of BCC and SCC was increased in CMM patients. The age-standardized prevalence of NMSCs and precursor lesions was higher in patients with CMM than in those without CMM, and was higher in CMM patients with immunosuppression (IS) than in those without IS. The association of M-Snomed subtypes, lentigo maligna (LM), melanoma in situ (MIS) and malignant melanoma (MM) with AK and/or BD was stronger than with BCC. LM revealed the highest association with the combination of AKBD-SCC. Male subjects showed a higher age-standardized prevalence of CMM, MM and BCC than females, but the opposite was observed for AK. Melanoma increases the risk of NMSCs, and IS may enhance this risk. Both malignant and in situ subtypes of melanoma associate with not only BCC and SCC, but also precancerous lesions.

Risk of skin cancer after ultraviolet phototherapy in patients with vitiligo: a systematic review and meta-analysis.

Although ultraviolet (UV) phototherapy is an effective treatment for vitiligo, its effect on the risk of skin cancer remains controversial. To investigate the association between UV phototherapy and skin cancer risk in patients with vitiligo. A systematic review was performed for studies published before 5 May 2021 in the PubMed, Embase, Web of Science and Cochrane Library databases. The primary outcome was the association of UV phototherapy with the risk of skin cancer in patients with vitiligo. A meta-analysis with a random-effects model was conducted. Five retrospective cohort studies covering a total of 228 607 patients with vitiligo (110 038 who had been treated with UV phototherapy and 118 569 patients who had not) were included in the meta-analysis. The risk of nonmelanoma skin cancer [Mantel-Haenszel risk ratio (MHRR) = 0.95; 95% CI 0.44-2.05] and melanoma (MHRR = 1.11; 95% CI 0.33-3.82) did not significantly increase after phototherapy in patients with vitiligo. In the subgroup analysis, we also found no significant association between phototherapy with narrowband UVB phototherapy specifically and risk of skin cancer in patients with vitiligo. There was no significant difference in risk of skin cancer between patients from Europe and those from East Asia and the risk was not affected by the number of narrowband UVB phototherapy sessions. The findings of this systematic review and meta-analysis suggest that UV phototherapy is a safe treatment for vitiligo with no significant risk of skin cancer.

Does hydrochlorothiazide increase the incidence of skin, lip and oral cancer in a UK population?

Data sources Data was from The Health Improvement Network (THIN) database from January 1999 to May 2016.Study selection This was a series of population-based, case-control studies looking to evaluate the association between hydrochlorothiazide (HCTZ) exposure and skin, lip and oral cancer in the UK population.Case/control selection Using the THIN database, patients with the following outcomes were grouped: squamous cell carcinoma (SCC) skin cancer; basal cell carcinoma (BCC) skin cancer; melanoma; lip cancer and oral cancer. Patients within the lip cancer and oral cancer groups were accepted with a history of non-melanoma skin cancer (NMSC). Patients in the SCC and BCC groups were not accepted with a history of cancer. Patients with a history of organ transplantation, human immunodeficiency virus (HIV) or immunosuppressant drug use before the index date were not accepted, due to the risk of predisposition to cancer. Controls were randomly selected using incidence density sampling. Up to 100 controls were randomly selected, matched on sex, exact year of birth and calendar year of cohort entry for lip cancer. However, for the remaining outcomes, only 20 controls were matched as above. Adults with incident NMSC, melanoma, lip cancer and oral cancer were matched to controls. Incidence rate ratios (IRRs) for the aforementioned outcomes were calculated for every cumulative HCTZ exposure.Data analysis Odds ratios were calculated using conditional logistic regression. Associations were presented using a two-year HCTZ exposure lag-time and a five-year HCTZ exposure lag-time. Associations were evaluated using sensitivity analysis, restricted to patients with at least ten years' follow-up. There was adjustment for smoking status and BMI. Published incidence rates were used to calculate the absolute risk estimate for SCC as the incidence of SCC in the cohort was less than expected. For high-dose cumulative HCTZ exposure, the number of patients needed to treat to cause one additional cancer (number needed to harm) per year overall was estimated using rate differences. Analysis was carried out using SAS Enterprise Guidev7.1 and STATAv15.Results Relative incidence of SCC, BCC and lip cancer was significantly elevated with every use of HCTZ. Relative incidence of melanoma and oral cancer was not significantly elevated with HCTZ exposure. Smoking was inversely associated with BCC and melanoma risk, but significantly increased the risk of lip and oral cavity cancers. SCC risk was not strongly associated with smoking. Significantly reduced risk of SCC, BCC melanoma and oral cavity cancer was associated with a BMI ≥30 kg/m2.Conclusions The risk of NMSC and lip cancer in a UK population is increased with cumulative high-dose HCTZ exposure. It is therefore important for dentists to note as it may increase suspicion of lesions in patients taking these medications.

Photoinduced skin reactions of cardiovascular drugs-a systematic review.

This systemic review aims to provide a practical overview of the prevalence, clinical manifestation, and management of adverse photoinduced skin reactions caused by frequently used cardiovascular drugs and to assess their potential relevance for skin cancer development. Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review of peer-reviewed studies reporting the photosensitizing and/or skin cancer-inducing properties of common cardiovascular drugs was performed and a guide to clinical management of photoinduced skin eruptions by cardiovascular drugs was provided. Study quality was assessed for major methodological biases. A total of 58 studies were identified (i.e. 23 case reports, 14 observational studies, 10 review articles, 10 experimental studies, and 1 meta-analysis). Most commonly, drug-associated adverse photoinduced cutaneous reactions were caused by phototoxic and photoallergic mechanisms. There is evidence suggesting that amiodarone and dronedarone, thiazide diuretics, thiazide-like diuretics, angiotensin receptor blockers, dihydropyridine-type calcium channel blockers, and certain angiotensin-converting enzyme inhibitors and statins may cause photoinduced adverse cutaneous reactions. Other drugs such as anticoagulants, antiplatelets, aldosterone antagonists, and fibrates have not been linked with photosensitizing reactions or adverse cutaneous reactions. Some drugs, i.e. thiazides and thiazide-like diuretics, were associated with an increased risk of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma). Certain commonly used cardiovascular drugs have been associated with adverse photoinduced cutaneous reactions. If they occur, further diagnosis and treatment might be needed, depending on the severity and progress. Whether photosensitizing drugs increase the risk of skin cancer remains elusive and further randomized controlled trials are required.

A164 RISKS OF SKIN CANCERS PRE- AND POST-INFLAMMATORY BOWEL DISEASE DIAGNOSIS

BackgroundInflammatory bowel disease (IBD) has been shown to be associated with an increased risk of non-melanoma skin cancers (NMSC), specifically squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), with the use of immunosuppressants such as thiopurines and tumor necrosis factor inhibitors (anti-TNFa). However, there is no literature exploring risk of skin cancers prior to formal Crohn’s disease (CD) or ulcerative colitis (UC) diagnoses. An increased risk pre IBD diagnosis could potentially suggest varied immunological impairments in patients with IBD.AimsTo compare risks of NMSC and melanoma preceding and following a diagnosis of IBD and to evaluate the effect of thiopurines and anti-TNFa on risk of skin cancers in IBD.MethodsThis is a retrospective, historical cohort study using population-based data sources including the University of Manitoba IBD Epidemiology Database and the Manitoba Cancer Registry. Individuals with IBD diagnosed between 1987 and 2018 (N = 9344 / 636 NMSC) were identified and matched with randomly selected controls (N = 88916 / 3839 NMSC) based on age, sex, and postal area of residence on the date of IBD diagnosis (index date). Logistic and Cox regression analyses were performed to calculate adjusted risks skin cancers prior to and after IBD diagnosis.ResultsSubjects with IBD were more likely to have BCC pre-dating their IBD diagnosis (OR 1.50, 95% CI 1.24–1.81). Risks of SCC, other non-melanoma skin cancers, or melanoma prior to IBD diagnosis were not significantly increased. Post-IBD diagnosis, risk of BCC and SCC were significantly increased across all IBD groups (HR 1.60, 95% CI 1.45–1.76 and HR 1.65, 95% CI 1.37–1.99), except for SCC in UC. There was no significant association between melanoma and IBD post-IBD diagnosis. Thiopurines are associated with higher risks of BCC, SCC, and melanoma in IBD. Anti-TNFa use also raised risks of BCC and melanoma, but anti-TNFa alone did not increase risk of SCC in IBD. Nested case-control analysis confirmed a higher baseline risk of BCC in patient with IBD with censoring of both thiopurines and anti-TNFa. Similarly, censoring of both medications produced no effect on risk of SCC in IBD corroborating the absence of a baseline SCC risk in IBD.ConclusionsThe risk of BCC preceding a formal diagnosis of IBD is higher than in non-IBD controls, compared to a generally increased risk of NMSC post-IBD diagnosis. IBD is not associated with a significant risk of melanoma, although risk for melanoma is increased with thiopurine or anti-TNFa exposure. Our study suggests a possible inherent immune impairment in patients with IBD that leads to BCC. Thiopurine and anti-TNF therapy increase the risks for skin cancers evident in persons with IBD after their diagnoses.Funding AgenciesNone

Characterizing dermatologic findings among patients with PTEN hamartoma tumor syndrome: Results of a multicenter cohort study

BackgroundDermatologic phenotypes in PTEN hamartoma tumor syndrome (PHTS) are heterogeneous and poorly documented. ObjectiveTo characterize dermatologic findings among PHTS and conduct an analysis of genotype-dermatologic phenotype associations. MethodsMucocutaneous findings were reviewed in a multicenter cohort study of PHTS. Genotype-dermatologic phenotype associations were tested using multivariable regression. ResultsA total of 201 patients were included. Children were significantly less likely than adults to have oral papillomas, vascular malformations, benign follicular neoplasms, and acral keratoses. There were no cases of skin cancer among children. Basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma developed in 5%, 2%, and 1% of White adults, respectively. After adjusting for age, missense mutations were associated with 60% lower odds of developing cutaneous papillomatous papules (odds ratio: 0.4; 95% confidence interval [0.2, 0.7]), oral papillomas (0.4; 95% confidence interval [0.2, 0.9]), and vascular malformations (0.4; 95% confidence interval [0.2, 0.8]). LimitationsPartly retrospective data. ConclusionChildren are less likely than adults to have certain dermatologic findings, likely due to age-related penetrance. The risk of pediatric melanoma and the lifetime risk of nonmelanoma skin cancer in PHTS may not be elevated. Missense variants may be associated with the development of fewer dermatologic findings but future validation is required.

P546 Minimal risk of lymphoma despite long term use of azathioprine in patients with Inflammatory Bowel Disease: a longitudinal cohort analysis from Northern India

Abstract Background Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn’s Disease (CD). Reported effectiveness and tolerability rates have been variable across studies. Moreover, there are only sparse data in the Asian population regarding the long-term efficacy and safety of azathioprine (AZT). Methods Records of 5351 patients followed up at IBD clinic, All India Institute of Medical Sciences, New Delhi from 2004–2020 were evaluated retrospectively. Azathioprine efficacy was defined as no requirement of surgery, hospitalizations, anti TNFs agents, and minimum steroid (≤1 course in 2 years) requirement on follow-up. Safety was evaluated in terms of long-term adverse events and the development of malignancy. Results Of 5351 patients with IBD, 1093 who received AZT for &amp;gt; 3 months (UC=788 [proctitis-1.9%, left-sided colitis-44.9%, pancolitis-53.1%], CD=305 [inflammatory-42.6%, stricturing-46.9%, fistulizing-10.5%]) were included (60.8%-males; mean age at disease onset-31.69±12.34 years) (Table1). Follow-up and treatment duration on AZT were 7(4–12) years and 39.41±40.27 months respectively. Mean initiation and maintenance dose of AZT was 1.09±0.45 mg/kg and 94.82±21.29, respectively. One,3,5, and 10 years relapse free survival was 85%,79%,76%, and 64%; 87%, 82%, 79% and 72%; and 78%, 72%, 68% and 61% in overall cohort, UC and CD patients, respectively (Log-rank P=0.001 between UC and CD). Three hundred fifty-nine [UC:249(31.6%); CD:110(36.07%); P=0.158] patients developed adverse events (AE), commonest was myelosuppression (23.42%) followed by gastrointestinal intolerance (2.97%), flu like illness (1.7%), and arthralgia/myalgia (1.37%) (Table 2). Myelosuppression was the commonest cause of AZT withdrawal. No patient (including 254 patients on AZT for ≥5 years) developed lymphoma or non-melanoma skin cancer. Adverse events free course in entire cohort, and in UC and CD are shown in fig.1 and 2 respectively. Conclusion Long-term Azathioprine monotherapy in patients with IBD is safe with minimal risk of lymphoma and non-melanoma skin cancer.

P456 Risk of malignant tumors in patients with autoimmune diseases on ustekinumab therapy: a systematic review and meta-analysis

Abstract Background Ustekinumab has shown efficacy in treating psoriasis, psoriatic arthritis, and inflammatory bowel disease and is generally safe in the short term; however, data on its long-term safety, especially in terms of malignant tumors, are lacking, which has aroused great public concern. Methods The PubMed, Web of Science, Embase, and Cochrane Library databases were searched from their establishment to July 2021 for randomized controlled trials (RCTs) reporting malignant tumors in adults with autoimmune diseases. Peto odds ratios (PORs) were calculated as effect sizes to assess the risk of malignant tumors. Results Fifteen RCTs involving 5835 patients were included in the study. The meta-analysis revealed that the risk of malignant tumors was not significantly different between patients treated with ustekinumab or placebo (POR=0.88, 95% confidence interval [CI] [0.37, 2.11], P=0.78). Similarly, no statistically significant difference existed in the incidence of non-melanoma skin cancers (POR=0.77, 95% CI [0.23, 2.61], P=0.68). No heterogeneity was observed in the comparisons. Conclusion Compared with placebo, ustekinumab did not increase the risk of malignant tumors or non-melanoma skin cancers in patients with autoimmune diseases, indicating the safety of this biological agent.

Inflammatory Bowel Disease Risk Variants Are Associated with an Increased Risk of Skin Cancer.

Inflammatory bowel disease is associated with an increased risk of skin cancer. The aims of this study were to determine whether IBD susceptibility variants are also associated with skin cancer susceptibility and if such risk is augmented by use of immune-suppressive therapy. The discovery cohort included participants in the UK Biobank. The validation cohort included participants in the Michigan Genomics Initiative. The primary outcome of interest was skin cancer, subgrouped into nonmelanoma skin cancers (NMSC) and melanoma skin cancers (MSC). Multivariable logistic regression with matched controls (3 controls:1 case) was performed to identify genomic predictors of skin malignancy in the discovery cohort. Variants with P <.05 were tested for replication in the validation cohort. Validated Single nucleotide polymorphisms were then evaluated for effect modification by immune-suppressive medications. The discovery cohort included 10,247 cases of NMSC and 1883 cases of MSC. The validation cohort included 7334 cases of NMSC and 3304 cases of MSC. Twenty-nine variants were associated with risk of NMSC in the discovery cohort, of which 5 replicated in the validation cohort (increased risk, rs7773324-A [DUSP22; IRF4], rs2476601-G [PTPN22], rs1847472-C [BACH2], rs72810983-A [CPEB4]; decreased risk, rs6088765-G [PROCR; MMP24]). Twelve variants were associated with risk of MSC in the discovery cohort, of which 4 were replicated in the validation cohort (increased risk, rs61839660-T [IL2RA]; decreased risk, rs17391694-C [GIPC2; MGC27382], rs6088765-G [PROCR; MMP24], and rs1728785-C [ZFP90]). No effect modification was observed. The results of this study highlight shared genetic susceptibility across IBD and skin cancer, with increased risk of NMSC in those who carry risk variants in IRF4, PTPN22, CPEB4, and BACH2 and increased risk of MSC in those who carry a risk variant in IL2RA.

Occupational ultraviolet light exposure increases the risk for non-melanoma skin cancer: Systematic Review and Meta-Analysis

Occupational ultraviolet light exposure increases the risk for non-melanoma skin cancer: Systematic Review and Meta-Analysis

Association of Non-Melanoma Skin Carcinomas and UV Exposure with Exfoliation Syndrome in Utah

Background: Prior data suggest an association between non-melanoma skin cancer, i.e., basal and squamous cell cancers most often located in areas of sun exposure, and pseudoexfoliation syndrome. This study aimed to evaluate the association between these conditions and UV exposure through a detailed questionnaire in a large and robust Utah population. Methods: The two arms of this study are a population-based study (evaluated via chart review) and a UV exposure study (evaluated via a questionnaire). Participants answered a questionnaire designed to assess lifelong UV exposure, including leisure and occupational sun exposure, likelihood to tan or burn in early life, eye and hair color, smoking behavior, vitamin D deficiency, skin cancer history, alcohol consumption, and caffeine intake. Conclusion: Descriptive findings suggest UV exposure over an adult’s lifespan may associate with a higher risk of non-melanoma skin cancer in Utah exfoliation patients vs. unaffected individuals. Patients with exfoliation glaucoma reside at higher elevations than non-glaucoma patients.

Arsenic and chromium levels in hair correlate with actinic keratosis/non-melanoma skin cancer: results of an observational controlled study.

The role of heavy metals in carcinogenetic process has been widely established; however, information on the most common environmental metals that serve as major risk factors for actinic keratosis (AK)/non-melanoma skin cancer (NMSC) are still lacking. The aim of this study was to evaluate levels of the most common environmental heavy metals in hair of patients with AK/NMSC as compared to healthy controls. Thirty-one patients diagnosed with AK/NMSC and 34 healthy controls were enrolled. Patients were interviewed for heavy metals exposure and underwent hair analysis for detection of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni) and lead (Pb). Continuous variables were analyzed using Wilcoxon Non-Parametric Rank Test and proportions were compared by Fisher's Exact Test. Statistical significance was determined by P<0.05. In our cohort we observed 48.4% patients had AKs, 16.1% basal cell carcinoma (BCC), 9.7% squamous cell carcinoma (SCC) and 25.9% of patients presented with a combination of these lesions. There were significantly elevated levels of As and Cr in AK-NMSC group as compared to controls. We identified a strong positive correlation between As and Cr concentration and AK/NMSC adding new clues to the scenery of NMSC risk factors that should be taken under consideration in exposed populations.