CANCER RISK IN SOLID ORGAN TRANSPLANT RECIPIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS

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. References: 1. Adami J, Gäbel H, Lindelöf B, et al. Cancer risk following organ transplantation: a nationwide cohort study in Sweden. Br J Cancer. 2003;89(7): 1221-1227. 2. Collett D, Mumford L, Banner NR, Neuberger J, Watson C. Comparison of the incidence of malignancy in recipients of different types of organ: a UK Registry audit. Am J Transplant. 2010;10(8): 1889-1896. 3. Engels EA, Pfeiffer RM, Fraumeni JF, Jr., et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA . 2011;306(17): 1891-1901. 4. Hortlund M, Arroyo Mühr LS, Storm H, Engholm G, Dillner J, Bzhalava D. Cancer risks after solid organ transplantation and after long-term dialysis. Int J Cancer. 2017;140(5): 1091-1101. 5. Na R, Grulich AE, Meagher NS, McCaughan GW, Keogh AM, Vajdic CM. Comparison of de novo cancer incidence in Australian liver, heart and lung transplant recipients. Am J Transplant. 2013;13(1): 174-183. 6. O’Neill JP, Sexton DJ, O’Leary E, et al. Post-transplant malignancy in solid organ transplant recipients in Ireland, The Irish Transplant Cancer Group. Clin Transplant. 2019;33(10): e13669-e13669. 7. Park B, Yoon J, Choi D, et al. De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data. Sci Rep. 2019;9(1): 17202-17202. 8. Serraino D, Piselli P, Busnach G, et al. Risk of cancer following immunosuppression in organ transplant recipients and in HIV-positive individuals in southern Europe. Eur J Cancer. 2007;43(14): 2117-2123. 9. Tsai H-I, Lee C-W, Kuo C-F, et al. De novo malignancy in organ transplant recipients in Taiwan: a nationwide cohort population study. Oncotarget. 2017;8(22): 36685-36695. 10. Wareham NE, Li Q, Sengeløv H, et al. “Risk of de novo or secondary cancer after solid organ or allogeneic haematopoietic stem cell transplantation”. J Cancer Res Clin Oncol. 2019;145(12): 3125-3135. 11. Agraharkar ML, Cinclair RD, Kuo Y-F, Daller JA, Shahinian VB. Risk of malignancy with long-term immunosuppression in renal transplant recipients. Kidney Int. 2004;66(1): 383-389. 12. Birkeland SA, Løkkegaard H, Storm HH. Cancer risk in patients on dialysis and after renal transplantation. Lancet . 2000;355(9218): 1886-1887. 13. Buxeda A, Redondo-Pachón D, Pérez-Sáez MJ, et al. Gender differences in cancer risk after kidney transplantation. Oncotarget . 2019;10(33): 3114-3128. 14. Cheung CY, Lam MF, Chu KH, et al. Malignancies after kidney transplantation: Hong Kong renal registry. Am J Transplant. 2012;12(11): 3039-3046. 15. Heo J, Noh OK, Oh Y-T, Chun M, Kim L. Cancer risk after renal transplantation in South Korea: a nationwide population-based study. BMC Nephrol. 2018;19(1): 311-311. 16. Hoshida Y, Tsukuma H, Yasunaga Y, et al. Cancer risk after renal transplantation in Japan. Int J Cancer. 1997;71(4): 517-520. 17. Kessler M, Jay N, Molle R, Guillemin F. Excess risk of cancer in renal transplant patients. Transpl Int. 2006;19(11): 908-914. 18. Kim JH, Kim S-O, Han DJ, Park S-K. Post-transplant malignancy: a burdensome complication in renal allograft recipients in Korea. Clin Transplant. 2014;28(4): 434-442. 19. Kyllönen L, Salmela K, Pukkala E. Cancer incidence in a kidney-transplanted population. Transpl Int. 2000;13 Suppl 1: S394-S398. 20. Li W-H, Chen Y-J, Tseng W-C, et al. Malignancies after renal transplantation in Taiwan: a nationwide population-based study. Nephrol Dial Transplant. 2012;27(2): 833-839. 21. Mazzucotelli V, Piselli P, Verdirosi D, et al. De novo cancer in patients on dialysis and after renal transplantation: north-western Italy, 1997-2012. J Nephrol. 2017;30(6): 851-857. 22. Opelz G, Unterrainer C, Süsal C, Döhler B. Immunosuppression with mammalian target of rapamycin inhibitor and incidence of post-transplant cancer in kidney transplant recipients. Nephrol Dial Transplant. 2016;31(8): 1360-1367. 23. Piselli P, Serraino D, Segoloni GP, et al. Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997-2009. Eur J Cancer. 2013;49(2): 336-344. 24. Ramsey-Goldman R, Brar A, Richardson C, et al. Standardised incidence ratios (SIRs) for cancer after renal transplant in systemic lupus erythematosus (SLE) and non-SLE recipients. Lupus Sci Med. 2016;3(1): e000156-e000156. 25. Schrem H, Schneider V, Kurok M, et al. Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control. PLoS One. 2016;11(7): e0158732-e0158732. 26. Teo SH, Lee K-G, Lim GH, et al. Incidence, risk factors and outcomes of malignancies after kidney transplantation in Singapore: a 12-year experience. Singapore Med J. 2019;60(5): 253-259. 27. Tessari G, Naldi L, Boschiero L, et al. Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study. Am J Transplant. 2013;13(1): 214-221. 28. Vajdic CM, McDonald SP, McCredie MRE, et al. Cancer incidence before and after kidney transplantation. JAMA . 2006;296(23): 2823-2831. 29. Villeneuve PJ, Schaubel DE, Fenton SS, Shepherd FA, Jiang Y, Mao Y. Cancer incidence among Canadian kidney transplant recipients. Am J Transplant. 2007;7(4): 941-948. 30. Aberg F, Pukkala E, Höckerstedt K, Sankila R, Isoniemi H. Risk of malignant neoplasms after liver transplantation: a population-based study. Liver Transpl. 2008;14(10): 1428-1436. 31. Baccarani U, Piselli P, Serraino D, et al. Comparison of de novo tumours after liver transplantation with incidence rates from Italian cancer registries. Dig Liver Dis. 2010;42(1): 55-60. 32. Chatrath H, Berman K, Vuppalanchi R, et al. De novo malignancy post-liver transplantation: a single center, population controlled study. Clin Transplant. 2013;27(4): 582-590. 33. Ettorre GM, Piselli P, Galatioto L, et al. De novo malignancies following liver transplantation: results from a multicentric study in central and southern Italy, 1990-2008. Transplant Proc. 2013;45(7): 2729-2732. 34. Heo J, Noh OK, Oh Y-T, Chun M, Kim L. Second primary cancer after liver transplantation in hepatocellular carcinoma: a nationwide population-based study. Hepatol Int. 2017;11(6): 523-528. 35. Hsiao C-Y, Lee P-H, Ho C-M, Wu Y-M, Ho M-C, Hu R-H. Post-transplant malignancy in liver transplantation: a single center experience. Medicine (Baltimore). 2014;93(28): e310-e310. 36. Jiang Y, Villeneuve PJ, Fenton SSA, Schaubel DE, Lilly L, Mao Y. Liver transplantation and subsequent risk of cancer: findings from a Canadian cohort study. Liver Transpl. 2008;14(11): 1588-1597. 37. Kaneko J, Sugawara Y, Tamura S, et al. De novo malignancies after adult-to-adult living-donor liver transplantation with a malignancy surveillance program: comparison with a Japanese population-based study. Transplantation . 2013;95(9): 1142-1147. 38. Maggi U, Consonni D, Manini MA, et al. Early and late de novo tumors after liver transplantation in adults: the late onset of bladder tumors in men. PLoS One. 2013;8(6): e65238-e65238. 39. Nordin A, Åberg F, Pukkala E, et al. Decreasing incidence of cancer after liver transplantation-A Nordic population-based study over 3 decades. Am J Transplant. 2018;18(4): 952-963. 40. Oo YH, Gunson BK, Lancashire RJ, Cheng KK, Neuberger JM. Incidence of cancers following orthotopic liver transplantation in a single center: comparison with national cancer incidence rates for England and Wales. Transplantation . 2005;80(6): 759-764. 41. Schrem H, Kurok M, Kaltenborn A, et al. Incidence and long-term risk of de novo malignancies after liver transplantation with implications for prevention and detection. Liver Transpl. 2013;19(11): 1252-1261. 42. Sérée O, Altieri M, Guillaume E, et al. Longterm Risk of Solid Organ De Novo Malignancies After Liver Transplantation: A French National Study on 11,226 Patients. Liver Transpl. 2018;24(10): 1425-1436. 43. Sheiner PA, Magliocca JF, Bodian CA, et al. Long-term medical complications in patients surviving > or = 5 years after liver transplant. Transplantation . 2000;69(5): 781-789. 44. Taborelli M, Piselli P, Ettorre GM, et al. Risk of virus and non-virus related malignancies following immunosuppression in a cohort of liver transplant recipients. Italy, 1985-2014. Int J Cancer. 2018;143(7): 1588-1594. 45. Jäämaa-Holmberg S, Salmela B, Lemström K, Pukkala E, Lommi J. Cancer incidence and mortality after heart transplantation - A population-based national cohort study. Acta Oncol. 2019;58(6): 859-863. 46. Jiang Y, Villeneuve PJ, Wielgosz A, Schaubel DE, Fenton SSA, Mao Y. The incidence of cancer in a population-based cohort of Canadian heart transplant recipients. Am J Transplant. 2010;10(3): 637-645. 47. Kellerman L, Neugut A, Burke B, Mancini D. Comparison of the incidence of de novo solid malignancies after heart transplantation to that in the general population. Am J Cardiol. 2009;103(4): 562-566. 48. Krynitz B, Edgren G, Lindelöf B, et al. Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish population-based study. Int J Cancer. 2013;132(6): 1429-1438. 49. Ekstrom M, Riise GC, Tanash HA. Risk of cancer after lung transplantation for COPD. International journal of chronic obstructive pulmonary disease. 2017;12: 2841-2847. 50. Fink AK, Yanik EL, Marshall BC, et al. Cancer risk among lung transplant recipients with cystic fibrosis. Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society. 2017;16(1): 91-97. 51. Magruder JT, Crawford TC, Grimm JC, et al. Risk Factors for De Novo Malignancy Following Lung Transplantation. Am J Transplant. 2017;17(1): 227-238. 52. Ohman J, Rexius H, Mjornstedt L, et al. Oral and lip cancer in solid organ transplant patients--a cohort study from a Swedish Transplant Centre. Oral Oncol. 2015;51(2): 146-150. 53. Jensen AO, Svaerke C, Farkas D, Pedersen L, Kragballe K, Sørensen HT. Skin cancer risk among solid organ recipients: a nationwide cohort study in Denmark. Acta Derm Venereol. 2010;90(5): 474-479. 54. Koshiol J, Pawlish K, Goodman MT, McGlynn KA, Engels EA. Risk of hepatobiliary cancer after solid organ transplant in the United States. Clin Gastroenterol Hepatol. 2014;12(9): 1541-1549.e1543. 55. Krynitz B, Olsson H, Lundh Rozell B, Lindelöf B, Edgren G, Smedby KE. Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study. Br J Dermatol. 2016;174(1): 95-103. 56. Mahale P, Shiels MS, Lynch CF, Engels EA. Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients. Am J Transplant. 2018;18(2): 453-461. 57. Park MJ, Roh J-L, Choi S-H, Nam SY, Kim SY, Lee YS. De novo head and neck cancer arising in solid organ transplantation recipients: The Asan Medical Center experience. Auris Nasus Larynx. 2018;45(4): 838-845. 58. Quinlan SC, Landgren O, Morton LM, Engels EA. Hodgkin lymphoma among US solid organ transplant recipients. Transplantation . 2010;90(9): 1011-1015. 59. Rizvi SMH, Aagnes B, Holdaas H, et al. Long-term Change in the Risk of Skin Cancer After Organ Transplantation: A Population-Based Nationwide Cohort Study. JAMA Dermatol. 2017;153(12): 1270-1277. 60. Robbins HA, Clarke CA, Arron ST, et al. Melanoma Risk and Survival among Organ Transplant Recipients. J Invest Dermatol. 2015;135(11): 2657-2665. 61. Safaeian M, Robbins HA, Berndt SI, Lynch CF, Fraumeni JF, Jr., Engels EA. Risk of Colorectal Cancer After Solid Organ Transplantation in the United States. Am J Transplant. 2016;16(3): 960-967. 62. Kalinova L, Majek O, Stehlik D, Krejci K, Bachleda P. Skin cancer incidence in renal transplant recipients - a single center study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154(3): 257-260. 63. Karami S, Yanik EL, Moore LE, et al. Risk of Renal Cell Carcinoma Among Kidney Transplant Recipients in the United States. Am J Transplant. 2016;16(12): 3479-3489. 64. Mäkitie AA, Lundberg M, Salmela K, Kyllönen L, Pukkala E. Head and neck cancer in renal transplant patients in Finland. Acta Otolaryngol. 2008;128(11): 1255-1258. 65. Medani S, O’Kelly P, O’Brien KM, Mohan P, Magee C, Conlon P. Bladder cancer in renal allograft recipients: risk factors and outcomes. Transplant Proc. 2014;46(10): 3466-3473. 66. Vajdic CM, van Leeuwen MT, McDonald SP, et al. Increased incidence of squamous cell carcinoma of eye after kidney transplantation. J Natl Cancer Inst. 2007;99(17): 1340-1342. 67. Vajdic CM, van Leeuwen MT, Turner JJ, et al. No excess risk of follicular lymphoma in kidney transplant and HIV-related immunodeficiency. Int J Cancer. 2010;127(11): 2732-2735. 68. Verran DJ, Mulhearn MH, Dilworth PJ, et al. Nature and outcomes of the increased incidence of colorectal malignancy after liver transplantation in Australasia. Med J Aust. 2013;199(9): 610-612. 69. Tessari G, Naldi L, Boschiero L, et al. Incidence and clinical predictors of Kaposi’s sarcoma among 1721 Italian solid organ transplant recipients: a multicenter study. Eur J Dermatol. 2006;16(5): 553-557. 70. Triplette M, Crothers K, Mahale P, et al. Risk of lung cancer in lung transplant recipients in the United States. Am J Transplant. 2019;19(5): 1478-1490. 71. Laprise C, Cahoon EK, Lynch CF, et al. Risk of lip cancer after solid organ transplantation in the United States. Am J Transplant. 2019;19(1): 227-237. 72. Morton LM, Gibson TM, Clarke CA, et al. Risk of myeloid neoplasms after solid organ transplantation. Leukemia . 2014;28(12): 2317-2323.

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