Cancer risk in heart or lung transplant recipients: A comprehensive analysis of 21 prospective cohorts.

We performed a meta-analysis to determine cancer risks at multiple sites and their associations with tumor mutation burden (TMB), an index for immunogenicity, in heart or lung transplant recipients. A comprehensive search of PubMed, Web of Science, EMBASE, and Medline was conducted. Random effects models were used to calculate standardized incidence ratios (SIRs) versus the general population and to determine the risks of different cancers. Weighted linear regression (WLR) was used to analyze the associations between the SIRs and TMBs. (PROSPERO CRD42020159599). Data from 21 studies including 116,438 transplant recipients (51,173 heart transplant recipients and 65,265 lung transplant recipients) with a total follow-up of 601,330.7 person-years were analyzed. Compared with the general population, heart transplant recipients displayed a 3.13-fold higher cancer risk [SIR: 3.13; 95% confidence interval (CI): 2.38-4.13; p < 0.001]; lung transplant recipients displayed a 4.28-fold higher cancer risk [SIR: 4.28; 95% CI: 3.18-5.77; p < 0.001]. The correlation coefficients were 0.54 (p = 0.049) and 0.79 (p < 0.001) in heart and lung transplant recipients, respectively, indicating that 29% and 63% of the differences in the SIRs for cancer types might be explained by the TMBs. Our study demonstrated that both heart and lung transplant recipients displayed a higher risk of certain site-specific cancers. These findings can provide individualized guidance for clinicians for detection of cancer among heart or lung transplantation recipients. In addition, we provided evidence that increased risks of post-transplant cancers can be attributed to immunosuppression.