Factors Associated with Risk of Clonal Haematopoiesis of Indeterminate Potential: A Systematic Review and...

Clonal haematopoiesis of indeterminate potential (CHIP) is a risk factor for blood cancers and non-haematological diseases. Understanding factors that lead to CHIP is essential in developing preventive strategies. We aimed to identify factors associated with risk of CHIP through a systemic literature review.

We searched MEDLINE and EMBASE for original studies reporting an age-adjusted risk measure for factors associated with an outcome of incident or prevalent CHIP. Random effects meta-analyses were performed for factors reported in at least three cohorts.

From 3305 abstracts, 26 studies were included, ranging from 118 to 239,216 participants. Risk of CHIP was higher in those with hypertension (Odds Ratio [OR] 1.1, 95% confidence interval 1.03-1.16), HIV infection (OR 2.37; 1.68-3.34), and smoking (OR 1.13; 1.10-1.17). The risk of CHIP was lower in those of Asian compared to White ethnicity (OR 0.73; 0.56-0.94). Male sex was not associated with risk of CHIP overall (OR 0.94; 0.86-1.03), but was associated with reduced risk of DNMT3A-CHIP (OR 0.82; 0.78-0.86) and increased risk of ASXL1-CHIP (OR 2.00; 1.76-2.27) or spliceosome-CHIP (OR 2.51; 2.03-3.11). We demonstrated no association between CHIP and diabetes, body mass index, or cardiovascular disease.

Our findings highlight the heterogeneity of CHIP, and suggest that factors associated with risk of CHIP differ between genes.

The authors have confirmed clinical trial registration is not needed for this submission.