INCIDENCE AND RISK FACTORS FOR DE-NOVO CANCERS IN ITALIAN KIDNEY TRANSPLANT (KT) RECIPIENTS

An excess of cancer risk among kidney transplant recipients has been well documented in several countries, including Italy. The yearly number of KTs carried on in Italy averages 1.500, but few large scale studies were conducted and none in the more recent years. To better quantify the risk of de novo cancers and to identify major risk factors for cancer occurrence we have carried out a multicenter investigation in 15 KT centers throughout Italy. A retrospective cohort study was implemented on 7143 individuals (64% men, median age 49.0 years ) who underwent KT between 1997 and 2007 and who were followed up thru December 2009. Through a standardized questionnaire, information was collected on socio demographic characteristics, clinical information regarding the transplant –including a detailed history of immunosuppressive treatments- , the diagnosis of neoplastic disease, and the vital status. Person years (PY) at risk of cancer were computed from 30 days after transplant to date of cancer diagnosis, death, return to dialysis or to study closure, whichever comes first. The number of observed cancer cases was compared with the expected one from National Cancer Registries through sex-, age-, area of residence- and period-standardized IR (SIR and 95% confidence intervals, CI). Incidence rate ratios (IRR) were computed through Poisson multivariate regression analysis to identify risk factors. The 7143 kidney transplant recipients included in this study summed up 39.280 PY at risk of cancer and 391 cancer diagnoses (13 patients had two cancers). Most of these cancers were solid tumors (255, of them lung, prostate and kidney cancers were the most common types), followed by Kaposi’s sarcoma (KS, 72 cases) and non-Hodgkin lymphoma (NHL, 39 cases). The overall incidence rate was 10.17 cases/10.000 PY and the excess risk, as compared to the general population of the same sex and age was 1.7 (95% CI: 1.6-1.9). Particularly elevated SIRs were noted for KS (136), NHL (4.5) and native kidney carcinomas (5.0). No excess risk was found for the cancers most commonly diagnosed in the general population of similar age and sex (e.g., lung, prostate, colon-rectum and breast carcinomas). Kidney transplant recipients who ever underwent immunosuppressive treatment with mTOR showed a 30% significantly reduced risk for all cancer types combined (SIR=0.70, 95% CI:0.51-0.97). The risk reduction was particularly evident for NHL (SIR=0.28) and kidney cancers (SIR==.48). Among the principal risk factors identified, it is worth mentioning that people born in southern Italy were at reduced risk for kidney cancer and NHL, whereas their risk of KS was higher than those born in northern Italy.