Genomic features do not account for differences in multiple myeloma risk by ancestry

Area of Science:

• Genomics
• Cancer Research
• Population Genetics

Background:

• Racial disparities in multiple myeloma (MM) incidence and outcomes are significant.
• The roles of germline variants and somatic genomic drivers in these disparities remain unclear.

Purpose of the Study:

• To investigate somatic drivers and inherited genetics in relation to MM disparities.
• To compare genomic differences between patients with African (AFR) and European (EUR) ancestry.

Main Methods:

• Combined whole-genome sequencing data from a new cohort with public datasets (total n = 1,286).
• Analyzed germline and somatic genomic alterations.
• Integrated epidemiological data and mutational signature analysis.

Main Results:

• No significant germline or somatic genomic differences were found to explain MM risk disparities between AFR and EUR groups.
• Observed differences in APOBEC-associated and germinal center mutational activity timing.
• Challenged the assumption of earlier MM onset in the AFR group using temporal estimates.
• Demonstrated equivalent clinical outcomes for AFR and EUR patients with equal therapy access.

Conclusions:

• Genomic factors do not appear to drive racial disparities in MM risk.
• Therapeutic access is a critical determinant of clinical outcomes.
• Further research should focus on non-genomic factors contributing to MM disparities.