Non-Malignant Hematologic Conditions and Subsequent Cancer Risk: A Prospective Cohort Study and Mendelian Randomization Analysis

No studies have examined the association between non-malignant hematologic diseases and the risk of various cancers. To examine the associations between non-malignant hematologic diseases and cancer risk, we performed a cohort study and mendelian randomization (MR) analysis. The association between hematologic diseases and incident cancer risk was assessed using time-varying Cox proportional hazards regression with multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Over a total of 5,031,372 person-years of follow-up in the UK Biobank, 32,589 (6.8%) patients were diagnosed with hematologic diseases, with 2,279 incident cancer cases. Multivariable time-varying Cox regression models revealed that any hematologic disease was positively associated with total cancer (HR=1.19; 95% CI, 1.14–1.24), hematologic cancer (HR=1.92; 95% CI, 1.69–2.17), and digestive system cancer risks (HR=1.36; 95% CI, 1.25–1.48). Nine hematologic diseases were associated with higher hematologic cancer risk, and six of the hematologic diseases were also associated with higher risks of four types of digestive system cancer (liver, stomach, esophageal, and small intestine cancers). MR analysis supported the positive association of agranulocytosis with leukemia, coagulation defects and spleen diseases with lymphoma, and unspecified anemia with small intestine cancer. This study indicates that non-malignant hematologic diseases are associated with an increased risk of cancer, particularly cancers in the hematological and digestive systems.