Dataset Information

Risk Factors for Developing Nonmelanoma Skin Cancer after Lung Transplantation.

ABSTRACT: Background:Nonmelanoma skin cancer (NSMC) is the most common malignancy after organ transplantation. Lung transplant recipients (LTRs) are particularly prone to develop NMSC as compared to renal or hepatic transplant recipients due to higher dosages of immunosuppression needed. Everolimus, an immunosuppressant used in organ transplant recipients, is thought to inherit a lower risk for NMSC than calcineurin inhibitors, especially in renal transplant recipients. It is currently unknown whether this also applies to LTRs. Objectives:To determine risk factors for NMSC and precancerous lesions after lung transplantation (LTx) and to characterize the effect of everolimus-based regimens regarding this risk. Materials and Methods:90 LTRs and former participants of the interventional trial "Immunosuppressive Therapy with Everolimus after Lung Transplantation", who were randomized to receive either an everolimus- or mycophenolate mofetil- (MMF-) based regimen, were enrolled and screened in this retrospective, single-center cohort study. Results:After a median follow-up of 101 months, we observed a prevalence of 38% for NMSC or precancerous lesions. 33% of the patients continuously receiving everolimus from LTx to dermatologic examination compared to 39% of all other patients, predominantly receiving an MMF-based regimen, were diagnosed with at least one NMSC or precancerous lesion (P=.66). Independent risk factors for NMSC or precancerous lesions after LTx were male sex and duration of voriconazole therapy. Conclusion:NMSC or precancerous lesions were very common after LTx, and risk factors were similar to previous reports on LTRs. Everolimus did not decrease this risk under the given circumstances of this study. Patients should be counseled regarding their risk, perform vigorous sunscreen, and undergo regular dermatological controls, regardless of their immunosuppressive regimen.

SUBMITTER: Grager N

PROVIDER: S-EPMC6431522 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Risk Factors for Developing Nonmelanoma Skin Cancer after Lung Transplantation.

Gräger Nikolai N Leffler Mareike M Gottlieb Jens J Fuge Jan J Warnecke Gregor G Gutzmer Ralf R Satzger Imke I

Journal of skin cancer 20190310

<h4>Background</h4>Nonmelanoma skin cancer (NSMC) is the most common malignancy after organ transplantation. Lung transplant recipients (LTRs) are particularly prone to develop NMSC as compared to renal or hepatic transplant recipients due to higher dosages of immunosuppression needed. Everolimus, an immunosuppressant used in organ transplant recipients, is thought to inherit a lower risk for NMSC than calcineurin inhibitors, especially in renal transplant recipients. It is currently unknown whe ...[more]

PMID: 30984427

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Project description:ImportanceImmune dysfunction underlies the pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunosuppressive therapy is the standard of care for these diseases. Both immune dysfunction and therapy-related immunosuppression can inhibit cancer-related immune surveillance in this population. Drug-induced immunosuppression is a risk factor for nonmelanoma skin cancer (NMSC), particularly squamous cell tumors. For patients with a history of NMSC, data are limited on the effect of these drugs on the risk of additional NMSCs.ObjectiveTo determine the relative hazard of a second NMSC in patients with RA or IBD who use methotrexate, anti-tumor necrosis factor (anti-TNF) therapy, or thiopurines after an initial NMSC.Design, setting, and participantsIn this retrospective cohort study, we studied 9460 individuals with RA or IBD enrolled in Medicare from January 1, 2006, through December 31, 2012.ExposuresExposure to methotrexate, thiopurines, anti-TNFs, sulfasalazine, hydroxychloroquine, abatacept, or rituximab after the incident NMSC surgery.Main outcomes and measuresA second NMSC occurring 1 year or more after the incident NMSC using Cox proportional hazards regression models.ResultsAmong 9460 individuals (6841 with RA and 2788 with IBD), the incidence rate of a second NMSC per 1000 person-years was 58.2 (95% CI, 54.5-62.1) and 58.9 (95% CI, 53.2-65.2) in patients with RA and IBD, respectively. Among patients with RA, methotrexate used in conjunction with other medications was associated with an increased risk of a second NMSC (hazard ratio [HR], 1.60; 95% CI, 1.08-2.37). Adjusted for other medications, the risk of NMSC increased with 1 year or more of methotrexate use (HR, 1.24; 95% CI, 1.04-1.48). Compared with methotrexate alone, the addition of anti-TNF drugs was significantly associated with risk of NMSC (HR, 1.49; 95% CI, 1.03-2.16). Abatacept and rituximab were not associated with increased NMSC risk. The nonsignificant HRs for 1 year or more of thiopurine and anti-TNF use for IBD were 1.49 (95% CI, 0.98-2.27) and 1.36 (95% CI, 0.76-2.44), respectively.Conclusions and relevanceMethotrexate use is associated with an increased risk of a second NMSC. Anti-TNF use may increase the risk of a second NMSC when used with methotrexate for RA. Further long-term studies are required before one can conclude that thiopurine and/or anti-TNF do not increase the risk of a second NMSC in patients with IBD.

Project description:Importance:Protective effects of UV-B radiation against nonmelanoma skin cancer (NMSC) are exerted via signaling mechanisms involving the vitamin D receptor (VDR). Recent studies have examined single-nucleotide polymorphisms (SNPs) in the VDR, resulting in contradictory findings as to whether these polymorphisms increase a person's risk for NMSC. Objective:To examine whether the polymorphisms in the VDR gene are associated with the development of NMSC and the demographic characteristics of the participants. Design, Setting, and Participants:This case-control study recruited 100 individuals who received a diagnosis of and were being treated for basal cell carcinoma or squamous cell carcinoma (cases) and 100 individuals who were receiving treatment of a condition other than skin cancer (controls) at the dermatology clinics at the Kirklin Clinic of the University of Alabama at Birmingham Hospital between January 1, 2012, and December 31, 2014. All participants completed a questionnaire that solicited information on skin, hair, and eye color; skin cancer family history; and sun exposure history, such as tanning ability and number of severe sunburns experienced throughout life. Blood samples for DNA genotyping were collected from all participants. Main Outcomes and Measures:Polymorphisms in the VDR gene (ApaI, BsmI, and TaqI) were assessed to determine the association of polymorphisms with NMSC development and demographic characteristics. ?2 Analysis was used to determine whether genotype frequencies deviated significantly from Hardy-Weinberg equilibrium. Logistic regression was used to calculate odds ratios (ORs) and associated 95% CIs for the identification of factors associated with NMSC diagnosis. A model was created to predict NMSC diagnoses using known risk factors and, potentially, VDR SNPs. Results:A total of 97 cases and 100 controls were included. Of the 97 cases, 68 (70%) were men and 29 (30%) were women, with a mean (SD) age of 70 (11) years. Of the 100 controls, 46 (46%) were men and 54 (54%) were women, with a mean (SD) age of 63 (9) years. All participants self-identified as non-Hispanic white. A model including age, sex, and skin color was created to most effectively predict the incidence of skin cancer. Risk factors that significantly increased the odds of an NMSC diagnosis were light skin color (OR,?5.79 [95% CI, 2.79-11.99]), greater number of severe sunburns (OR,?2.59 [95% CI, 1.31-5.10]), light eye color (OR, 2.47 [95% CI, 1.30-4.67]), and less of an ability to tan (OR,?2.35 [95% CI, 1.23-4.48]). The risk factors of family history of NMSC (OR,?1.66 [95% CI, 0.90-3.07]) and light hair color (OR,?1.17 [95% CI, 0.51-2.71]) did not reach statistical significance. Participants with the BsmI SNP were twice as likely to develop NMSC than participants with no mutation (OR, 2.04 [95% CI, 1.02-4.08]; P?=?.045). Conclusions and Relevance:The results of this study are especially useful in the early treatment and prevention of NMSC with chemopreventive agents (for those with the BsmI SNP). A screening for the BsmI SNP may emphasize the importance of sun protection and facilitate skin cancer prevention and, therefore, decrease the skin cancer burden.

Project description:Melanocortin-1 receptor (MC1R) gene variants are associated with fair skin and red hair and, independently of these, with cutaneous malignant melanoma. The association of MC1R gene variants with nonmelanoma skin cancer is largely unknown. A total of 838 subjects were included in the present study: 453 patients with nonmelanoma skin cancer and 385 subjects with no skin cancer. The coding sequence of the human MC1R gene was tested using single-stranded conformation polymorphism analysis followed by sequencing of unknown variants. Risk of skin cancer dependent on the various MC1R gene variants was estimated using the exposure odds ratio. We investigated whether subjects with MC1R variant alleles were at increased risk of developing nonmelanoma skin cancer and, if so, whether this increased risk was mediated by fair skin and red hair. A total of 27 MC1R gene variants were found. The number of carriers of one, two, or three MC1R gene variants was 379 (45.2%), 208 (24.8%), and 7 (0.9%), respectively. A strong association between MC1R gene variants and fair skin and red hair was established, especially the variants Arg151Cys and Arg160Trp (P < .0001). Carriers of two variant alleles were at increased risk for developing cutaneous squamous cell carcinoma (odds ratio 3.77; 95% confidence interval [CI] 2.11-6.78), nodular basal cell carcinoma (odds ratio 2.26; 95% CI 1.45-3.52), and superficial multifocal basal cell carcinoma (odds ratio 3.43; 95% CI 1.92-6.15), compared with carriers of two wild-type alleles. Carriers of one variant allele had half the risk. The highest relative risks of nonmelanoma skin cancer were found in carriers of the Asp84Glu, His260Pro, and Asp294His variant alleles, and the risk was only slightly lower for carriers of the Val60Leu, Val92Met, Arg142His, Arg151Cys, and Arg160Trp variant alleles. When subjects were stratified by skin type and hair color, analysis showed that these factors did not materially change the relative risks. These findings indicate that MC1R gene variants are important independent risk factors for nonmelanoma skin cancer.

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Risk Factors for Developing Nonmelanoma Skin Cancer after Lung Transplantation.

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Risk Factors for Developing Nonmelanoma Skin Cancer after Lung Transplantation.

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