Clonal Hematopoiesis and Incident Solid Cancers Resolved by Histologic Subtype: A Prospective Cohort Study

Clonal hematopoiesis is linked to higher risk of incident solid cancers in UK Biobank, with strongest histologic subtype signals for esophageal squamous cell carcinoma (HR 2.28).

• Why it matters: CHIP is established for myeloid malignancy and cardiovascular risk, but its relationship to solid tumors—especially by histologic subtype—remains incompletely defined.
• What they did: In a prospective UK Biobank cohort with baseline genetic sequencing and cancer ascertainment via national registry linkage (excluding pre-baseline cancer), CHIP associations were tested by clone size, mutation number, and histologic subtype; Vanderbilt BioVU replicated findings.
• The result: CHIP associated with any incident cancer (HR 1.22) and all solid tumors combined (HR 1.13), with lung adenocarcinoma (HR 1.79) and esophageal squamous cell carcinoma (HR 2.28) surviving multiple-testing correction; risk rose with clone size and multi-hit CHIP, and the esophageal squamous association persisted in a 5-year landmark analysis (HR 2.57).

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