Calcineurin Inhibitors Decrease DNA Repair and Apoptosis in Human Keratinocytes Following Ultraviolet B Irradiation

Yarosh, Daniel B.; Peña, Arely V.; Nay, Stephanie L.; Canning, Matthew T.; Brown, David A.

doi:10.1111/j.0022-202x.2005.23858.x

Cited by 182 publications

(150 citation statements)

References 30 publications

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“…Azathioprine sensitizes DNA to ultraviolet A radiation, 66 reducing the minimal erythema dose in skin cells of treated patients, 67,68 while cyclosporine inhibits DNA repair and apoptosis in ultraviolet B radiation-exposed human keratinocytes. 69,70 However, exposure to either of these agents has not been consistently associated with an increased risk of NMSC.…”

Section: Nonmelanoma Skin Cancermentioning

confidence: 99%

Cancer incidence and risk factors after solid organ transplantation

Vajdic

Leeuwen

2009

Intl Journal of Cancer

381

253

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Iatrogenic immunosuppression is a unique setting for investigating immune-related mechanisms of carcinogenesis. Solid organ transplant recipients have a 3-fold excess risk of cancer relative to the age-and sex-matched general population. Population-based studies utilizing cancer registry records indicate that a wide range of cancers, mostly those with a viral etiology, occur at excess rates. To date, cancer risk has predominantly been examined in adult kidney transplant recipients in Western countries. It is yet to be established whether a similar incidence profile exists in the longterm for other solid organ, pediatric and non-Western transplant recipients. The cancer incidence profile before and after kidney transplantation strongly suggests a relatively minor contribution by both preexisting cancer risk factors and the conditions underlying end-stage kidney disease, and points to a causal role for immunosuppression. Within-cohort risk factor analyses have largely been performed on cohorts with voluntary cancer notification, and very few have incorporated biomarkers of the level of immunosuppression, the current receipt of immunosuppressive agents, or genetic risk factors. Because of their markedly high risk of certain cancers, findings from comprehensive studies in transplant recipients have the potential to raise new avenues for investigation into causal mechanisms and preventive measures against immunerelated and infectious causes of cancer. ' UICCKey words: cancer; transplantation; immunosuppression; incidence; risk; infection; kidney A wide-ranging excess risk of cancer after solid organ transplantation has been increasingly recognized over recent decades as advances in medicine have extended the life of transplant recipients. Malignancy is now a leading cause of patient death with graft function, 1-3 an outcome that can predominantly be attributed to the iatrogenic immunosuppression required to avoid rejection of the transplanted organ. Solid organ transplantation provides a unique setting for the identification of cancers under immunological control, and for examination of the risk factors for their development. Knowledge of the range of increased cancers and the magnitude of the increased risks is important in developing appropriate prevention and early detection programs for patients undergoing long-term immunosuppression. In addition, comparison of cancer incidence and risk factors between populations with different forms of immune system impairment offers insight into carcinogenic mechanisms that has ramifications for cancer control not only in these populations but also in the general community.This review focuses on the cancer incidence profile in solid organ transplant recipients, and the established and emerging risk factors for 5 cancers that occur at increased rates. Cancer incidence after solid organ transplantationShortly after the widespread introduction of solid organ transplantation, it became apparent that immune suppression was associated with a strikingly increased risk of a few canc...

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Section: Nonmelanoma Skin Cancermentioning

confidence: 99%

Cancer incidence and risk factors after solid organ transplantation

Vajdic

Leeuwen

2009

Intl Journal of Cancer

381

253

View full text Add to dashboard Cite

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“…[32][33][34] While immunosuppression appears to be the principal predisposing factor, others have argued that compounds such as CsA can also inhibit the repair of DNA damage. 33,[35][36][37] A precedent for the role of immunosuppressive agent-induced DNA damage likely impacting on cancer predisposition has recently been described regarding azathioprine. 38,39 Unrepaired DSBs can result in deletions and/or act as a platform for translocations with obvious implications for malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

CsA can induce DNA double-strand breaks: implications for BMT regimens particularly for individuals with defective DNA repair

O’Driscoll

Jeggo

2008

Bone Marrow Transplant

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“…One of the potential mechanisms of carcinogenesis includes direct effect of TCIs on keratinocytes inhibiting spontaneous DNA repair and reducing apoptosis in healthy human epidermal keratinocytes following UV-B irradiation (29). However, in preclinical studies the topical use of TCI was not associated with any mutagenic, genotoxic and photocarcinogenic effects (30,31).…”

Section: Tcis and Theoretical Malignancy Risk Factorsmentioning

confidence: 99%

Topical Calcineurin Inhibitors and Malignancy Risk

et al. 2017

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Context: The approval of topical calcineurin inhibitors (TCIs) has been a significant breakthrough for the treatment of atopic dermatitis due to much lower systemic absorption and not causing skin atrophy even after long-term use that have made them become popular replacements for topical corticosteroids being almost equally effective. In January 2006, the US food and drug administration (FDA), followed later also by the European medicine agency (EMEA), issued the "black box" warning causing controversy regarding a potential increased risk of lymphoma in patients with atopic dermatitis and treated with TCIs. Evidence Acquisition: PubMed and MEDLINE ® databases were systematically searched utilizing a variety of terms relating to the subject matter. Articles written only in English over the past 15 years were analyzed and selected for review. Results: So far, no scientific evidence of the association has been found between use of TCIs, and increased incidence of skin cancers and lymphomas in patients with AD. The systematic review and meta-analysis by Legendre et al. found the role of TCIs unlikely to be a significant risk factor of lymphoma in those patients. Conclusions:Despite an extensive body of evidence regarding the TCIs safety, the box warning still remains leaving the physicians and patients unduly uncertain and confused about the safety of TCI use.

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Calcineurin Inhibitors Decrease DNA Repair and Apoptosis in Human Keratinocytes Following Ultraviolet B Irradiation

Cited by 182 publications

References 30 publications

Cancer incidence and risk factors after solid organ transplantation

Cancer incidence and risk factors after solid organ transplantation

CsA can induce DNA double-strand breaks: implications for BMT regimens particularly for individuals with defective DNA repair

Topical Calcineurin Inhibitors and Malignancy Risk

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