Spectrum of cancer risk among US solid organ transplant recipients

Abstract

Context: Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology.

Objective: To describe the overall pattern of cancer following solid organ transplantation.

Design, setting, and participants: Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries.

Main outcome measures: Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population.

Results: The registry linkages yielded data on 175,732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10,656 cases and an incidence of 1375 per 100,000 person-years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100,000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100,000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6-178.4] per 100,000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100,000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100,000 person-years), liver (n = 930; incidence: 120.0 per 100,000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0-117.6] per 100,000 person-years), and kidney (n = 752; incidence: 97.0 per 100,000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3-83.3] per 100,000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74-2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57-3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]).

Conclusion: Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.

Figure 1

Risk of non-Hodgkin lymphoma following transplantation. Standardized incidence ratios and associated 95% confidence intervals are shown according to time since transplantation and transplanted organ. The vertical axis shows the standardized incidence ratios on a log-scale. Results are presented for all transplants (solid circle), kidney transplants (open square), liver transplants (open circle), heart transplants (open triangle), and lung transplants (open diamond). The number of observed cancer events is shown below the figure; corresponding expected counts are presented in eTable 1.

Figure 2

Risk of lung cancer following transplantation. Standardized incidence ratios and associated 95% confidence intervals are shown according to time since transplantation and transplanted organ. The vertical axis shows the standardized incidence ratios on a log-scale. Results are presented for all transplants (solid circle), kidney transplants (open square), liver transplants (open circle), heart transplants (open triangle), and lung transplants (open diamond). The number of observed cancer events is shown below the figure; corresponding expected counts are presented in eTable 1.

Figure 3

Risk of liver cancer following transplantation. Standardized incidence ratios and associated 95% confidence intervals are shown according to time since transplantation and transplanted organ. The vertical axis shows the standardized incidence ratios on a log-scale. Results are presented for all transplants (solid circle), kidney transplants (open square), liver transplants (open circle), heart transplants (open triangle), and lung transplants (open diamond). The number of observed cancer events is shown below the figure; corresponding expected counts are presented in eTable 1. Standardized incidence ratios are off-scale and therefore not presented for 0.01–0.50 years after transplantation, for all transplants combined (standardized incidence ratio 126.11, 95%CI 117.69–134.98) and for liver transplants (standardized incidence ratio 508.97, 95%CI 474.16–545.66). For some other estimates, the standardized incidence ratio was zero and so cannot be shown on the log-scale. When the standardized incidence ratio was zero, the upper confidence limit is displayed, with the exception of the estimate for lung transplants at 10.01–15.00 years after transplant, for which the upper limit is also off-scale (95% upper confidence interval 49.64).

Figure 4

Risk of kidney cancer following transplantation. Standardized incidence ratios and associated 95% confidence intervals are shown according to time since transplantation and transplanted organ. The vertical axis shows the standardized incidence ratios on a log-scale. Results are presented for all transplants (solid circle), kidney transplants (open square), liver transplants (open circle), heart transplants (open triangle), and lung transplants (open diamond). The number of observed cancer events is shown below the figure; corresponding expected counts are presented in eTable 1. For some estimates, the standardized incidence ratio was zero and so cannot be shown on the log-scale. When the standardized incidence ratio was zero, the upper confidence limit is displayed, with the exception of the estimate for lung transplants at 10.01–15.00 years after transplant, for which the upper limit is also off-scale (95% upper confidence interval 32.73).