Dissecting the molecular signatures underlying sex bias in clonal hematopoiesis and blood malignancies

Human cancers develop through the successive acquisition of somatic genetic mutations and clonal evolution, often over the course of many years.

Clonal hematopoiesis of indeterminate potential (CHIP) is a pre-cancerous state where pathogenic somatic variations occur in the blood cells of healthy individuals.

CHIP is present in 15% of the elderly population and is associated with a higher risk of blood malignancies, mortality, and age-related diseases (e.g., cardiovascular diseases).Incidence, prognosis, and mortality in blood cancer are higher in males than in females.

Interestingly, the prevalence of several autosomal gene mutations (e.g., DNMT3A, ASXL1, SRSF2, etc.) is sex-biased in CHIP and blood cancer.

The mechanisms underlying the sex bias in CHIP and blood cancer remain unknown.In this project, we will study how sex-specific context (hormones, sex chromosome genetics, and lifestyle) influence the development of CHIP and blood cancer.

We will perform a large-scale genomic analysis of DNA sequencing data from approximately 500,000 individuals.The project will be carried out at Sahlgrenska Academy (University of Gothenburg) in collaboration with Lund University. The project will uncover novel mechanisms influencing the development of CHIP and blood malignancies.

The findings will provide new insights into the causes of sex bias in cancer and may provide opportunities for therapeutic interventions in the longer term.