Cancer risk in solid organ transplant recipients: A systematic review and meta-analysis
Zhenyu Huo1, Fan Ge2, Runchen Wang1, Yaokai Wen1, Hengrui Liang4, Yu Jiang1, Zixuan Su1, Wenhua Liang3, Jianxing He4.
1Nanshan School, Guangzhou Medical University, Guangzhou, People's Republic of China; 21st Clinical School, Guangzhou Medical University, Guangzhou, People's Republic of China; 3Department of Thoracic Oncology, The 1st Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China; 4Department of Thoracic Surgery, The 1st Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
Introduction: Patients underwent solid organ transplantation are observed to be associated with an increased cancer risk. However, the specific cancer risks in solid organ recipients remain unclear. Tumor mutational burden (TMB) is a measure of immunogenicity of certain cancer.
Materials and Methods: English-language studies in PubMed, Web of Science, EMBASE, Medline were searched. Random-effects model meta-analyses were used to calculate standardized incidence ratios (SIRs) for solid organ transplant recipients compared with the general population, stratified by types of transplantation. Linear regression (LR) was used to analyze the associations between tumors’ standardized incidence ratios (SIRs) and corresponding tumor mutational burden (TMB).
Results and Discussion: 72 articles met our criteria. Based on data from 2,105,122 patients, we observed 45 types of cancer risk in solid organ transplant recipients. 34 of them were statistically significant. Compared with general population, solid organ transplant recipients displayed a 2.68-fold higher cancer risk (SIR, 2.68 [CI, 2.48 to 2.89]); renal transplant recipients displayed a 2.56-fold cancer risk (SIR, 2.56 [CI, 2.31 to 2.84]); liver transplant recipients displayed a 2.45-fold cancer risk (SIR, 2.45 [CI, 2.22 to 2.70]); heart and/or lung transplant recipients displayed a higher cancer risk (SIR, 3.72 [CI, 3.04 to 4.54]) (Table 1).
In solid organ transplant recipients, we observed a significant correlation between the tumor mutational burden (TMB) and the standardized incidence ratios (SIRs). The correlation coefficient of 0.67 [P<0.001], 0.61 [P<0.001], 0.61 [P<0.001], and 0.73 [P<0.001] in solid organ transplant recipients, renal transplant recipients, liver transplant recipients and heart and/or lung transplant recipients, respectively, suggested that 45%, 37%, 37%, and 53% of the differences in the standardized incidence ratios across cancer types may be explained by the tumor mutational burden, respectively (Figure 1).
Conclusion: Our study demonstrated that solid organ transplant recipients displayed an increase of general cancer risk and different risk of malignancy at multiple sites. This risk profile can provide guidance for the post-transplant follow-up strategy of cancer among solid organ transplantation recipients. In addition, we showed evidence that the risk of different malignancies was associated with tumor mutational burden, suggesting that the increase of post-transplant malignancy was attributed to the intervention of immunosuppression.
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