Skin tumours in the West of Scotland renal transplant population

Mackintosh, Lorna; Geddes, Colin C.; Herd, R. M.

doi:10.1111/bjd.12129

Cited by 14 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fact that cumulative dosage of cyclosporine and other immunosuppressants is independently associated with risk of non-cutaneous cancers in OTRs tends to support this theory 19,20 . The best example of the association between immunosuppression and increased skin cancer risk comes from patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS).…”

Section: Skin Cancer In Organ Transplant Recipientsmentioning

confidence: 93%

Skin cancer in organ transplant recipients: More than the immune system

Wheless

Jacks

Potter

et al. 2014

Journal of the American Academy of Dermatology

View full text Add to dashboard Cite

Organ transplant recipients (OTRs) are at increased risk of developing non-melanoma skin cancers (NMSC). This has long been thought to be due to immunosuppression and viral infection. However, skin cancer risk among individuals with AIDS or iatrogenic immunodeficiency does not approach the levels seen in OTRs, suggesting other factors play a critical role in oncogenesis. In clinical trials of OTRs, switching from calcineurin inhibitors to mammalian Target of Rapamycin (mTOR) inhibitors consistently led to a significant reduction in the risk of developing new skin cancers. New evidence suggests calcineurin inhibitors interfere with p53 signaling and nucleotide excision repair. These two pathways are associated with NMSC, and squamous cell carcinoma (SCC) in particular. This finding may help explain the predominance of SCC over basal cell carcinoma in this population. mTOR inhibitors do not appear to impact these pathways. Immunosuppression, viral infection, and impaired DNA repair and p53 signaling all interact in OTRs to create a phenotype of extreme risk for NMSC.

show abstract

Section: Skin Cancer In Organ Transplant Recipientsmentioning

confidence: 93%

Skin cancer in organ transplant recipients: More than the immune system

Wheless

Jacks

Potter

et al. 2014

Journal of the American Academy of Dermatology

View full text Add to dashboard Cite

show abstract

“…OTRs rely on immunosuppressive drug therapy to ensure the long‐term survival and function of their transplanted organs. The use of multiple immunosuppressive drugs in combination and the necessity for long periods of immunosuppression has led to an increased incidence of NMSC formation . Indeed, malignancy is now the commonest cause of death in renal transplant patients in Australia .…”

Section: Nmsc Risk Is Associated With Immunosuppression Regimementioning

confidence: 99%

“…The use of multiple immunosuppressive drugs in combination and the necessity for long periods of immunosuppression has led to an increased incidence of NMSC formation. [10][11][12][13] Indeed, malignancy is now the commonest cause of death in renal transplant patients in Australia. 14 Reducing immunosuppression may reduce the risk of skin cancer development, but needs to be counterbalanced by the increased risk of allograft rejection.…”

Section: Nmsc Risk Is Associated With Immunosuppression Regimementioning

confidence: 99%

Does the nature of residual immune function explain the differential risk of non‐melanoma skin cancer development in immunosuppressed organ transplant recipients?

Jung

Overgaard

Burke

et al. 2015

Intl Journal of Cancer

View full text Add to dashboard Cite

Patients receiving immunosuppression to prevent organ transplant rejection are at a greatly increased risk of developing nonmelanoma skin cancer. In recent years a correlation has been identified between the class of immunosuppressant that these patients receive and their subsequent cancer risk; in particular, patients switched from calcineurin inhibitors to mammalian target of rapamycin (mTOR) inhibitors not only displayed a dramatic reduction in new tumor formation but also in some cases a regression of their existing lesions. Studies of cancer models in mice and cell lines in the laboratory have attributed these discrepancies in cancer risk to the ability of immunosuppressants such as mTOR inhibitors to elicit direct anticancer effects, including suppressing angiogenesis and increasing autophagy‐mediated DNA repair. Recent evidence from the immunological literature however, suggests a significant alternative contribution of mTOR inhibitors; namely the promotion of memory T‐cell function. Recent advances in understanding memory T‐cell establishment and the demonstration of their critical role in long‐term immunity make it timely to review the available evidence as to whether the improved nonmelanoma skin cancer outcome shown by patients switched to mTOR inhibitor treatment regimens may be associated with the retainment of memory T‐cell function.

show abstract

“…The majority of included studies were deemed to be high quality (5,6,21,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). Ten were assessed as medium quality (2,3,7,20,(48)(49)(50)(51)(52)(53), and two were low quality (54,55) (Table S2).…”

Section: Quality Assessmentmentioning

confidence: 99%

“…Ten cohort studies and one clinic-based case-control study reported on the association between azathioprine risk and various other skin cancers. The risk of melanoma was evaluated in six studies (5,45,46,52,54,55), MCC in three (6,52,54), KS in five (20,46,49,52,53) and other rare skin cancers (e.g. atypical fibroxanthoma, B cell lymphoma) in four studies (20,45,52,54).…”

Section: Risk Of Other Skin Cancersmentioning

confidence: 99%

Azathioprine and Risk of Skin Cancer in Organ Transplant Recipients: Systematic Review and Meta-Analysis

Jiyad

Olsen

Burke

et al. 2016

American Journal of Transplantation

165

102

View full text Add to dashboard Cite

Azathioprine, a purine antimetabolite immunosuppressant, photosensitizes the skin and causes the production of mutagenic reactive oxygen species. It is postulated to increase the risk of squamous cell carcinoma (SCC) and other skin cancers in organ transplant recipients (OTRs), but evidence from multiple, largely single-center studies to date has been inconsistent. We aimed to resolve the issue of azathioprine's carcinogenicity by conducting a systematic review of the relevant literature and pooling published risk estimates to evaluate the risks of SCC, basal cell carcinoma (BCC), keratinocyte cancers (KCs) overall and other skin cancers in relation to azathioprine treatment. Twenty-seven studies were included in total, with risk estimates from 13 of these studies able to be pooled for quantitative analysis. The overall summary estimate showed a significantly increased risk of SCC in relation to azathioprine exposure (1.56, 95% confidence interval [CI] 1.11-2.18). No significant associations between azathioprine treatment and BCC (0.96, 95% CI 0.66-1.40) or KC (0.84, 95% CI 0.59-1.21) risk were observed. There was significant heterogeneity between studies for azathioprine risk estimates and the outcomes of SCC, BCC and KC. The pooled findings of available evidence support the contention that treatment with azathioprine increases the risk of SCC in OTRs.

show abstract

Skin tumours in the West of Scotland renal transplant population

Abstract: This is the first study of skin cancer in prevalent Scottish RTRs. The incidence of skin cancer is high and appears to have a direct relationship to the overall burden of immunosuppression. The SCC:BCC ratio, which is lower than reports from other centres, deserves further scrutiny.

Cited by 14 publications

References 29 publications

Skin cancer in organ transplant recipients: More than the immune system

Skin cancer in organ transplant recipients: More than the immune system

Does the nature of residual immune function explain the differential risk of non‐melanoma skin cancer development in immunosuppressed organ transplant recipients?

Azathioprine and Risk of Skin Cancer in Organ Transplant Recipients: Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About