Evidence map›Paper›PMID 41607022›Full record

ArticleInternational journal of cancer2026

Cumulative exposure to tacrolimus is associated with increased risk of malignancy for solid organ transplant recipients.

Sergio A Acuna, Xun Zhao, Maggie Jones-Carr, Graham Smith, Kyla Naylor, Bima J Hasjim, Shiyi Chen, An-Wen Chan, Nancy Baxter, S Joseph Kim and 1 more

Abstract read
In one paragraph

Article in International journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Sergio A AcunaDivision of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Xun ZhaoAjmera Transplant Centre, University Health Network, Toronto, Ontario, Canada.
Maggie Jones-CarrDivision of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Graham SmithICES Western, London Health Sciences Centre Research Institute, London, Ontario, Canada.
Kyla NaylorICES Western, London Health Sciences Centre Research Institute, London, Ontario, Canada.
Bima J HasjimDepartment of Surgery, University of California-Irvine, Orange, California, USA.
Shiyi ChenDepartment of Biostatistics, University Health Network, Toronto, Ontario, Canada.
An-Wen ChanDivision of Dermatology, Department of Medicine and Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.
Nancy BaxterFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
S Joseph KimDivision of Nephrology, University Health Network, University of Toronto, Toronto, ON, Canada. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
Mamatha BhatAjmera Transplant Centre, University Health Network, Toronto, Ontario, Canada.

Funding

Deep South KUH Premier Research - Interdisciplinary Mentored Education (PRIME) Training CoreTL1DK139566 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DAVID M POLLOCK · 2023 to 2026
$3.6M
Deep South KUH Premier Research- Interdisciplinary Mentored Education (PRIME) Networking CoreU2CDK133422 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Orlando M Gutierrez · 2023 to 2026
$2.8M
NIDDK NIH HHS TL1 DK139566NIDDK NIH HHS U2C DK133422University Health Network
6 · The paper itself

Abstract

Solid organ transplant recipients (SOTR) face elevated cancer risk due to prolonged immunosuppression. While higher tacrolimus exposure has been linked to de novo malignancies, the dose-response relationship remains unclear, prompting the need for population-level, longitudinal investigations. To quantify the exposure-response relationship between tacrolimus trough level and post-transplant malignancy risk, we used a population-based cohort study using linked administrative healthcare data from Ontario, Canada. All transplant recipients from January 1, 2008 to March 1, 2020 with ≥2 serum tacrolimus levels in the first year post-transplant were included. Cumulative exposure to tacrolimus was treated as a (1) continuous variable, (2) by quartiles of exposure within the first year and (3) as time-varying exposure beyond the first year; incidence of de novo malignancy was investigated using cause-specific and subdistribution Cox regression models. Among the 5178 SOTRs, a total of 318 de novo malignancies (6.1%) and 332 deaths (6.4%) occurred. For every 20% increase in the cumulative tacrolimus trough level in the first year, a heightened risk of malignancy was observed (HR = 1.09, 95% CI: 1.02-1.17). For each 20% increase in cumulative tacrolimus trough level after 1 year, the risk of malignancy increased (HR = 1.08 [95% CI: 1.01-1.15]). Patients in the highest quartile of cumulative exposure (median 9-10 ng/mL) had a 47% greater risk of malignancy compared to those in the lowest quartile (median 5-6 ng/mL; HR = 1.47 [95% CI: 1.03-2.11]). These findings highlight the importance of carefully titrating tacrolimus and avoiding unnecessary prolonged high exposure, particularly during the critical first year post-transplant.

Indexed as

Immunosuppressive AgentsNeoplasmsOrgan TransplantationTacrolimusTransplant RecipientsAdultAgedCohort StudiesFemaleGraft RejectionHumansIncidenceMaleMiddle AgedOntarioRisk FactorsImmunosuppressive AgentsTacrolimuscancerimmunosuppressionsolid organ transplanttacrolimus

Identifiers

PMID41607022
PMCPMC13106907

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.