Association of Pre-Diagnostic Clonal Hematopoiesis of Indeterminate Potential With Prognosis Among Patients With Cancer.

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) might impair prognosis of several cancer types. Since previous studies predominantly focused on CHIP after cancer diagnosis, little is known about whether CHIP prior to cancer diagnosis predicts outcome. We performed a prospective cohort study, including 63 486 patients with cancer during 2006 to 2022 in the UK Biobank, to evaluate the association between pre-diagnostic CHIP and survival of cancer patients. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. We identified 2860 patients with cancer and pre-diagnostic CHIP, and 60 626 cancer patients without CHIP. During a median follow-up of 4.2 years, 1162 patients died in the CHIP group (921 cancer-specific deaths), and 17 825 in the reference group (14 785 cancer-specific deaths). Cancer patients with pre-diagnostic CHIP exhibited a higher rate of overall death (HR 1.18, 95% CI: 1.11-1.25) and cancer-specific death (HR 1.17, 95% CI: 1.09-1.25) compared with the reference group. A significant association of both overall death and cancer-specific death was observed for myeloproliferative neoplasms, multiple myeloma, breast cancer, non-Hodgkin lymphoma, and acute myeloid leukemia/myelodysplastic syndromes. The increased rate of both overall death and cancer-specific death was noted for CHIP with TET2, SRSF2, or JAK2 mutation. These findings suggested extended clinical awareness in cancer patients with pre-diagnostic CHIP.