The Epidemiology of Transplant-Associated Keratinocyte Cancers in Different Geographical Regions

Proby, Charlotte M.; Wisgerhof, Hermina C.; Casabonne, Delphine; Green, Adèle C.; Harwood, Catherine A.; Bavinck, Jan Nico Bouwes

doi:10.1007/978-0-387-78574-5_7

Cited by 19 publications

(30 citation statements)

References 79 publications

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“…and Marcen et al. , might be due to the darker skin types in such populations being relatively protective against SCC but less so against BCC; 26 however, in our study the majority of patients had the fairer skin types I–III. There appears to be an exponential rise in the incidence of SCC, but a linear rise in BCC following transplantation 7,9 .…”

Section: Discussioncontrasting

confidence: 74%

“…Based on differences in the SCC:BCC ratio seen at different latitudes within Australia, 25 it has been suggested that the level of sun exposure influences the proportion of BCCs and SCCs observed following transplantation, with increasing SCCs related to increased sun exposure 26 . SCCs are typically associated with chronic UVR exposure, whereas BCCs are related to short, intense bursts of UVR such as those obtained on sunny holidays.…”

Section: Discussionmentioning

confidence: 99%

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Skin tumours in the West of Scotland renal transplant population

2013

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Skin tumours in the West of Scotland renal transplant population

2013

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“…The lowest rates are reported for OTRs from Africa, East Asia and India. Taken together, these data point to the protective effect of darker skin pigmentation (also see ‘UV susceptibility’ below). This is illustrated by the much less significant burden of KC among Asian OTRs.…”

Section: Demography and Demographic Trendsmentioning

confidence: 62%

Epidemiology of keratinocyte carcinomas after organ transplantation

et al. 2017

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SummaryKeratinocyte carcinoma (KC) is the most common type of cancer among white populations, but it is even more common among solid organ transplant recipients (OTRs). The most frequent histological type of KC among OTRs is cutaneous squamous cell carcinoma (cSCC), followed by basal cell carcinoma, although the reverse is seen in the general population. Metastatic cSCCs are more frequent, and mortality is increased compared with immunocompetent populations. There is strong evidence that the risk of KC among OTRs rises with increasing time after transplantation and older age at transplantation, and that KC is enhanced in those with sun-damaged skin. This evidence suggests that accelerated accumulation of genetic damage from several sources leads to excess KC in OTRs. We describe international variation in KC and focus on trends in immunosuppressive regimens, the role of ultraviolet susceptibility and exposure, and the contribution of genetics to tumour development. Further epidemiological studies are needed to address gaps in our understanding of the mediation of excess KC by immunosuppressive drugs, viral infection, genetic susceptibility, timing of relevant ultraviolet exposure or some combination of these factors.

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“…Whereas the thiopurines (azathioprine, 6-mercaptopurine, and 6-thioguanine) are highly effective anti-inflammatory, immunosuppressive, and anticancer agents, their long-term use is associated with increased risk (in some cases by more than 100-fold) for the development of squamous cell carcinoma of the skin (20)(21)(22)(23). Within an individual patient, the tumors are usually multiple, affect large areas of the skin, frequently relapse, and often metastasize, causing a very significant morbidity and even mortality (24).…”

Section: Introductionmentioning

confidence: 99%

Highly Potent Activation of Nrf2 by Topical Tricyclic Bis(Cyano Enone): Implications for Protection against UV Radiation during Thiopurine Therapy

Kalra

Knatko

Zhang

et al. 2012

Cancer Prevention Research

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Chronic treatment with azathioprine, a highly effective anti-inflammatory and immunosuppressive agent, profoundly increases the risk for development of unusually aggressive cutaneous squamous cell carcinoma. Its ultimate metabolite, 6-thioguanine (6-TG) nucleotide, is incorporated in DNA of skin cells, and upon exposure to UVA radiation, causes oxidative stress, followed by damage of DNA and associated proteins. The acetylenic tricyclic bis(cyano enone) TBE-31 is a strong inhibitor of inflammation and a potent inducer of the Keap1/Nrf2/ARE pathway, which orchestrates the expression of a large network of cytoprotective genes. We now report that long-term (five days per week for four weeks) topical daily applications of small (200 nmol) quantities of TBE-31 cause a robust systemic induction of the Keap1/Nrf2/ ARE pathway and decreases the 6-TG incorporation in DNA of skin, blood, and liver of azathioprine-treated mice, indicating extraordinary bioavailability and efficacy. In addition, TBE-31, at nanomolar concentrations, protects cells with 6-TG in their genomic DNA against oxidative stress caused by UVA radiation through induction of the Keap1/Nrf2/ARE pathway. At the same 6-TG DNA levels, Keap1-knockout cells, in which the pathway is constitutively upregulated, are highly resistant to UVA radiation-induced oxidative stress. The protective effects of both the Keap1-knockout genotype and TBE-31 are completely lost in the absence of transcription factor Nrf2. Our findings suggest that compounds of this kind are excellent candidates for mechanism-based chemoprotective agents against conditions in which oxidative stress and inflammation underlie disease pathogenesis. Moreover, their potential skin patch incorporation for transdermal delivery is an exciting possibility. Cancer Prev Res; 5(7); 973-81. Ó2012 AACR.

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The Epidemiology of Transplant-Associated Keratinocyte Cancers in Different Geographical Regions

Cited by 19 publications

References 79 publications

Skin tumours in the West of Scotland renal transplant population

Skin tumours in the West of Scotland renal transplant population

Epidemiology of keratinocyte carcinomas after organ transplantation

Highly Potent Activation of Nrf2 by Topical Tricyclic Bis(Cyano Enone): Implications for Protection against UV Radiation during Thiopurine Therapy

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