Cancer patients have an increased risk of developing venous thromboembolism (VTE) and this combination is reported to result in poorer survival compared to cancer alone. The aim of this study was to investigate the impact of VTE on survival of cancer patients in a general population. The Scandinavian Thrombosis and Cancer (STAC) cohort, a population-based cohort including 144,952 subjects without previous VTE or cancer was used. During follow-up, cancer and VTE incidences were registered. 'Cancer-related VTE' was defined as VTE diagnosed in patients with overt or occult cancer. Survival of subjects without cancer and/or VTE ('disease-free') was compared with survival of subjects with cancer and cancer-related VTE. Cox-regression models with cancer and VTE as time-varying exposures were performed to calculate hazard ratios for death. Sub-analyses were performed across cancer types and stages and VTE type (deep vein thrombosis or pulmonary embolism). During follow-up (mean 11.7 years) 14,621 subjects developed cancer and 2,444 developed VTE, of which 1241 where cancer-related. The mortality rates (per 100 person-years) for disease-free subjects, VTE only, cancer only and cancer-related VTE were 0.63 (95%CI 0.62-0.65), 5.0 (4.6-5.5), 9.2 (9.0-9.5) and 45.3 (41.1-50.0), respectively. Compared with cancer only patients, the risk of death for cancer-related VTE patients was increased 3.4-fold (95%CI 3.1-3.8). Within all cancer types, the occurrence of VTE increased the mortality risk 2.8 to 14.7-fold. In a general population, cancer patients with VTE had a 3.4-fold higher mortality risk than cancer patients without VTE, independent of cancer type.

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Background Colorectal cancer patients have an increased risk of developing venous thromboembolism (VTE), resulting in increased morbidity and mortality. Because the exact mechanism is yet unknown, risk prediction is still challenging; therefore, new biomarkers are needed. MicroRNAs (miRNAs) are small, relatively stable RNAs, that regulate a variety of cellular processes, and are easily measured in body fluids. Objective The aim of this study was to identify novel tumor‐expressed miRNAs associated with VTE. Methods In a cohort of 418 colorectal cancer patients diagnosed between 2001 and 2015 at the Leiden University Medical Center, 23 patients (5.5%) developed VTE 1 year before or after cancer diagnosis. Based on availability of frozen tumor material, tumor cells of 17 patients with VTE and 18 patients without VTE were isolated using laser capture microdissection and subsequently analyzed on the Illumina sequencing platform NovaSeq600 using 150‐bp paired‐end sequencing. Cases and controls were matched on age, sex, tumor stage, and grade. Differential miRNA expression was analyzed using edgeR. Results A total of 547 miRNAs were detected. Applying a 1.5‐fold difference and false discovery rate of <0.1, 19 tumor‐miRNAs were differentially regulated in VTE cases versus controls, with hsa‐miR‐3652, hsa‐miR‐92b‐5p, and hsa‐miR‐10,394‐5p as most significantly downregulated. Seven of the 19 identified miRNAs were predicted to regulate the gonadotropin‐releasing hormone receptor pathway. Conclusion We identified 19 differentially regulated tumor‐expressed miRNAs in colorectal cancer‐associated VTE, which may provide insights into the biological mechanism and in the future might have potential to serve as novel, predictive biomarkers.