Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non‐melanoma skin cancer in an at‐risk population: A cohort study

Setshedi, Mashiko; Epstein, David; Winter, Trevor A.; Myer, Landon; Watermeyer, Gillian; Hift, Richard

doi:10.1111/j.1440-1746.2011.06865.x

Cited by 94 publications

(69 citation statements)

References 35 publications

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“…[19][20][21] An increased incidence of skin cancer has also been observed in diseases such as inflammatory bowel disease, where active immunosuppressive agents similar to those in OTRs are used. 22,23 Against this background, it becomes very obvious that adequate photoprotection is the key to reducing the harmful effects of UVR. This article provides background information on (i) UVR, (ii) photoprotection, including the concept of topical sunscreen formulations, (iii) associated concerns regarding efficacy and safety and (iv) behavioural and educational aspects of photoprotection and skin cancer prevention in immunocompetent and immunocompromised people.…”

Section: Discussionmentioning

confidence: 99%

Photoprotection in immunocompetent and immunocompromised people

Surber

Ulrich

Hinrichs³

et al. 2012

British Journal of Dermatology

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SummaryUltraviolet radiation (UVR) exposure from the sun and artificial UV sources has been widely acknowledged as the major culprit for skin cancer and premature skin ageing. Skin cancers are among the most dangerous (cutaneous malignant melanoma) and the most numerous (basal cell carcinoma, actinic keratosis and invasive squamous cell carcinoma) of all neoplasms in the caucasian population worldwide. Skin cancers therefore have a significant impact on public health and healthcare costs, and will continue to do so. It is obvious that adequate photoprotection -seeking shade, wearing protective clothing and using sunscreens -is the key to reducing the harmful effects of UVR in both immunocompetent and immunocompromised people. This article provides background information on UVR, photoprotection (including the concept of topical sunscreen formulations), associated concerns regarding efficacy and safety, and behavioural and educational aspects of photoprotection and skin cancer prevention in immunocompetent and immunocompromised people. Certain persistent misconceptions and mistakes regarding photoprotection are also addressed.Ultraviolet radiation (UVR) exposure from the sun and artificial UV sources has been widely acknowledged as the major culprit for skin cancer and premature skin ageing.

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Section: Discussionmentioning

confidence: 99%

Photoprotection in immunocompetent and immunocompromised people

Surber

Ulrich

Hinrichs³

et al. 2012

British Journal of Dermatology

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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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“…Trois autres études ont confirmé le risque élevé de ce cancer chez patients atteints de MICI sous thiopurines [22][23][24].…”

Section: Le Risque De Malignitéunclassified

Les effets indésirables des thiopurines au cours du traitement d’entretien de la maladie de Crohn

Gamrani¹,

Krati²

2017

Hegel

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Use of thiopurines in the treatment of inflammatory bowel disease is associated with an increased risk of non‐melanoma skin cancer in an at‐risk population: A cohort study

Abstract: Patients with IBD who receive thiopurines are at increased risk of non-melanoma skin cancer. The risk is highest in Caucasian patients, and is negligible in other groups.

Cited by 94 publications

References 35 publications

Photoprotection in immunocompetent and immunocompromised people

Photoprotection in immunocompetent and immunocompromised people

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

Les effets indésirables des thiopurines au cours du traitement d’entretien de la maladie de Crohn

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