Risks of Multiple Skin Cancers in Organ Transplant Recipients

Wehner, Mackenzie R.; Niu, Jiangong; Wheless, Lee; Baker, Laura X.; Cohen, Olivia; Margolis, David J.; Giordano, Sharon H.; Shin, Thuzar M.

doi:10.1001/jamadermatol.2021.4148

Cited by 16 publications

(13 citation statements)

References 20 publications

(44 reference statements)

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“…There was no significant difference in the mean number of skin cancers among those with or without voriconazole exposure in the present cohort in any of the models. We were limited by the lack of generalizability of a single-center study, although the results suggesting increased rates of skin cancer after the first skin cancer agree with those reported in a previous study that used 2 large, administrative databases . We also go beyond these previous findings by addressing the competing risk of death and stratifying by transplanted organ type.…”

Section: Discussionmentioning

confidence: 96%

Differences in Skin Cancer Rates by Transplanted Organ Type and Patient Age After Organ Transplant in White Patients

et al. 2022

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ImportanceAlthough it is known that patients with thoracic organ transplants develop skin cancer more frequently than those who receive nonthoracic organ transplants, patterns of risk for subsequent skin cancers are unknown.ObjectiveTo further characterize organ transplant recipients who develop multiple skin cancers and assess for patterns of development of additional skin cancers beyond the first skin cancer diagnosis by patient age and transplanted organ type.Design, Setting, and ParticipantsThis cohort study used validated electronic health record–based data from a single tertiary care academic medical center to identify 5129 solid organ transplant recipients who underwent transplant surgery between 1992 and 2017 and were older than 18 years at the time of transplant. The cohort was limited to White patients because they have the highest skin cancer risk based on phenotype. The mean follow-up was 6.6 years. Data were analyzed June 9, 2021, to May 31, 2022.Main Outcomes and MeasuresDifferences in rates of skin cancer development for first and subsequent skin cancers were measured using t test or analysis of variance and χ2 tests for continuous and categorical variables. Rates of skin cancer development were compared based on organ type and patient age at transplant using Fine-Gray tests and cumulative incidence plots.ResultsA total of 5129 organ transplant recipients (mean [SD] age, 51.3 [12.9] years; 3287 men [64.1%]) were included. Of these, 695 patients (13.6%) had development of at least 1 skin cancer, with 6842 skin cancers identified in the cohort overall. Compared with liver transplant recipients, heart, lung, or kidney recipients were more likely to develop at least 1 skin cancer (χ2 test, 25.6; df, 4; P &lt; .001). There was no significant difference by transplanted organ type in the rate of developing a second or third skin cancer; however, the age at transplant was associated with the time to developing a second (χ2 test, 20.4; df, 4; P &lt; .001) or third (χ2 test, 10.9; df, 4; P &lt; .02) skin cancer.Conclusions and RelevanceThis cohort study found that there was no difference by organ type for development of subsequent skin cancers in organ transplant recipients, and recipients of all organ types developed additional skin cancers at high rates after the initial skin cancer.

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Section: Discussionmentioning

confidence: 96%

Differences in Skin Cancer Rates by Transplanted Organ Type and Patient Age After Organ Transplant in White Patients

et al. 2022

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“…Cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous malignancy. Rates in organ transplant recipients (OTRs) are 60 to 250 times that in the general population 1 2 3 4 . Following an initial skin cancer diagnosis, 50% of OTRs developed a second tumor within 2 years 4 .…”

Section: Epidemiology Of Cutaneous Squamous Cell Carcinoma In Organ T...mentioning

confidence: 99%

“…Rates in organ transplant recipients (OTRs) are 60 to 250 times that in the general population 1 2 3 4 . Following an initial skin cancer diagnosis, 50% of OTRs developed a second tumor within 2 years 4 . There is a tendency for tumors, especially cSCC, to develop at sites with pre-existing keratotic lesions 5 .…”

Section: Epidemiology Of Cutaneous Squamous Cell Carcinoma In Organ T...mentioning

confidence: 99%

The Tumor Immune Microenvironment in Cutaneous Squamous Cell Carcinoma Arising in Organ Transplant Recipients

et al. 2023

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Cutaneous squamous cell carcinoma (cSCC) is the most common malignancy in immune-suppressed organ transplant recipients (OTRs). Whilst rates of other malignancies (both cutaneous and non-cutaneous) are elevated in this population, the increase is far less striking. This suggests that cSCC must be a highly immunogenic tumor. The tumor immune microenvironment is altered in cSCC from OTRs. It has reduced anti-tumor properties and instead provides an environment that facilitates tumor growth and survival. Understanding the composition and function of the tumor immune microenvironment in cSCC from OTRs is useful for prognostication and therapeutic decisions.

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“…Solid organ transplant recipients (SOTRs) have up to 100-fold and 20-fold increased risk for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), respectively compared to the general population 1 . In addition, the majority (57%) of SOTRs develop multiple skin cancers 2 . Studies have demonstrated that advanced age, male sex, fair skin, excessive ultraviolet radiation (UV) damage, red and blonde hair are significant predictors of SCC and BCC risk 3 .…”

Section: Introductionmentioning

confidence: 99%

Re-weightingMC1R, ASIPandIRF4risk variants optimises polygenic risk scores for keratinocyte cancer stratification in solid organ transplant recipients

Seviiri

Law

Olsen

et al. 2023

Preprint

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Introduction: Solid organ transplant recipients (SOTRs) are at much higher risk of developing squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), compared to the general population. Previous studies have derived genetics-based predictors (polygenic risk scores, PRS) of SCC and BCC risk in SOTRs by assuming that genetic risk variants act in the same way in the general population as in SOTRs, but this assumption has not been fully tested. Objective: To investigate whether known genetic risk variants for SCC and BCC have different effect sizes in SOTRs versus in non-transplantees, and if a re-weighted PRS would improve risk prediction. Methods: We conducted genome-wide association studies for SCC and BCC separately in the non-transplant general population and in SOTRs, and compared the risks associated with selected common genetic variants for KC risk in SOTR vs non-transplant individuals from the UK Biobank. For regions with an increased log odds ratio in SOTRs, PRSs including these weights were validated in the QSkin study, and applied to the Australian STAR SOTR cohort. Results: Effect sizes for functional variants in MC1R (rs1805007), ASIP (rs6059655), and IRF4 (rs12203592) were much more strongly associated with the risk of KC in SOTRs than in non-transplantees. The proportional increase in the effect sizes ranged from 1.9-fold for rs6059655 and BCC risk (SOTRs log (OR)=0.49, 95%CI=0.00-0.98 vs log (OR)=0.26, 95%CI=0.24-0.30 in non-transplantees) to as high as 4.8-fold for rs1805007 and SCC risk (SOTR log (OR)=0.88, 95% CI=0.41-1.35 vs log (OR)=0.18, 95% CI=0.12-0.24 in non-transplantees). PRS with SOTR derived weights for these SNPs showed improved SCC/BCC risk stratification in the STAR Cohort, with the optimised PRS reclassifying 19% of SCC cases vs 8% using the standard PRS, and 18% of BCC cases vs 12% using the standard PRS. Conclusion: Effect sizes for SCC and BCC risk for genetic variants in the MC1R, ASIP and IRF4 genes are elevated in SOTRs, and correctly weighting these variants improves risk stratification based on polygenic risk.

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Risks of Multiple Skin Cancers in Organ Transplant Recipients

Cited by 16 publications

References 20 publications

Differences in Skin Cancer Rates by Transplanted Organ Type and Patient Age After Organ Transplant in White Patients

Differences in Skin Cancer Rates by Transplanted Organ Type and Patient Age After Organ Transplant in White Patients

The Tumor Immune Microenvironment in Cutaneous Squamous Cell Carcinoma Arising in Organ Transplant Recipients

Re-weightingMC1R, ASIPandIRF4risk variants optimises polygenic risk scores for keratinocyte cancer stratification in solid organ transplant recipients

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