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Published on: November 8, 2015
Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis
Elizabeth L Yanik1, Kulsoom Siddiqui1,2, Eric A Engels1
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Abstract:
Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR] = 0.71, 95% CI = 0.56-0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR = 0.49, 95% CI = 0.32-0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR = 0.19, 95% CI = 0.04-0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR = 1.06, 95% CI = 0.69-1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR = 0.40, 95% CI = 0.20-0.81), and higher prostate cancer incidence (IRR = 1.85, 95% CI = 1.17-2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk.
Insights
Sirolimus use in kidney transplant recipients is linked to reduced nonmelanoma skin cancer (NMSC) risk, especially when replacing cyclosporine. However, it may increase prostate cancer risk while potentially lowering kidney cancer risk.
Area of Science:
- Nephrology
- Oncology
- Immunology
Background:
- Sirolimus is an immunosuppressant used in kidney transplantation.
- Its potential to reduce cancer risk via mTOR pathway inhibition requires further investigation.
- Previous studies on sirolimus and cancer incidence in kidney recipients are inconclusive and lack specificity for cancer types.
Purpose of the Study:
- To systematically review and meta-analyze randomized controlled trials (RCTs) and observational studies on sirolimus use and cancer incidence in kidney transplant recipients.
- To evaluate the association between sirolimus and overall cancer incidence, as well as specific cancer types.
- To stratify findings by study type and concomitant use of cyclosporine.
Main Methods:
- Systematic literature review and meta-analysis of RCTs and observational studies.
- Inclusion of studies comparing sirolimus users with nonusers in kidney transplant recipients.
- Pooled incidence rate ratios (IRRs) were calculated for total cancer and specific cancer types, stratified by study design and cyclosporine use.
Main Results:
- Twenty-two studies involving 39,039 kidney recipients were analyzed.
- Sirolimus use was associated with a significant reduction in overall cancer incidence (IRR = 0.71).
- This reduction was primarily driven by a decrease in nonmelanoma skin cancer (NMSC) incidence (IRR = 0.49), with a stronger effect when sirolimus replaced cyclosporine (IRR = 0.19).
- No significant association was found for other cancers excluding NMSCs (IRR = 1.06).
- Sirolimus use was linked to lower kidney cancer incidence (IRR = 0.40) but higher prostate cancer incidence (IRR = 1.85).
Conclusions:
- Sirolimus use in kidney transplant recipients is associated with a reduced risk of NMSC, potentially enhanced by avoiding cyclosporine.
- Sirolimus may decrease kidney cancer risk but does not appear to protect against other cancers and may increase prostate cancer risk.
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