Objective The clinical characteristics and survival of patients with myeloproliferative neoplasms (MPNs) with secondary cancer were analyzed to explore the possible risk factors for secondary cancer in MPN patients. Methods The clinical characteristics of 1060 Chinese patients with MPN were retrospectively analyzed. The Kaplan-Meier method was used to analyze the survival. The Cox multivariate regression model was used to analyze the risk factors for developing secondary cancer in patients with MPNs. The GO and KEGG databases were used to mine biological information, identify genetic associations and perform correlation analysis. Results 28.1% (298/1060) of 1060 MPN patients died. The median survival times of the PV, ET and PMF groups were 20, 24 and 12 years, respectively (P<0.0001). Fifty-seven patients developed secondary cancers, and the incidences at 5, 10 and 15 years were 1.8%, 3.4%, and 4.1%, respectively. There were 44 cases of secondary solid tumor, 7 cases of secondary lymphoma, 1 case of secondary multiple myeloma, 1 case of secondary plasma cell tumor and 4 cases of secondary cancer of an unknown type. In age- and sex-matched healthy Chinese patients, the standardized incidence ratio (SIR) value of developing secondary cancer in MPN patients was 6.41 (95% CI: 4.90-9.48). The median survival time was 14 years in the MPN with secondary cancer group and 19 years in the MPN without secondary cancer group (P=0.001). KEGG signaling pathway enrichment analysis showed that some genes in the noncancer group are enriched in viral infection-related signaling pathways, while some genes in the cancer group are enriched in microRNA-related pathways and epigenetics-related gene mutations. The Cox multivariate analysis showed that age ≥65 years (P<0.0001, HR=5.027, 95% CI [2.823, 8.952]), MF-1 (P=0.001, HR=2.887, 95% CI [1.503, 5.545]) were risk factors for developing secondary cancer. Conclusions Compared with normal subjects, MPN patients had a 6.41-fold increased risk of developing secondary cancer, and age ≥65 years and MF-1 were risk factors for developing secondary cancer in MPN patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal