A GENOME-WIDE association study has identified a variant in the MAVS gene associated with Kaposi sarcoma (KS) in people living with HIV, providing the first evidence of inherited susceptibility in children and highlighting a potential biological pathway involved in disease development.
KS is a cancer of the blood vessel lining that is driven by infection with human herpesvirus-8 (HHV-8), with immune deficiency recognised as a key contributing factor. However, because most people with these risk factors do not develop the disease, researchers investigated whether inherited genetic variation may also influence susceptibility.
The finding was observed in both paediatric and adult cohorts living with HIV, supporting further investigation into the role of host genetics in KS susceptibility in high-burden settings.
Genetic Clues Beyond Established Risk Factors
The discovery phase included 45 perinatally HIV-infected children with KS and 91 controls, with researchers analysing single-nucleotide variants across the genome after quality control.
The strongest signal was a missense variant in the mitochondrial antiviral-signalling (MAVS) gene, rs7269320, which showed a suggestive association with KS. The variant was associated with increased odds of KS (OR 3.8, 95% CI 2.2–6.7; p=9.7×10⁻⁷).
The association was replicated in an independent cohort of 215 adults living with HIV with KS and 262 controls. The same MAVS variant showed a recessive inheritance pattern, with an odds ratio of 2.2 (95% CI 1.2–3.9; p=0.006).
A Biologically Plausible Pathway for Kaposi Sarcoma
MAVS is a component of the RIG-I/MAVS signalling pathway, which plays an important role in antiviral immune responses. MAVS protein dysfunction or deficiency is known to impair antiviral cytokine responses to HHV-8 infection and enhance viral reactivation, making the pathway a biologically plausible contributor to KS oncogenesis.
The findings represent the first paediatric evidence of germline susceptibility to KS and identify the RIG-I/MAVS pathway as a candidate pathway influencing susceptibility to KS.
However, the investigators emphasised that further replication and functional studies are required to clarify how the MAVS variant influences disease risk. Future studies will also need to determine whether the variant could help identify people at highest risk of KS in high-burden settings or inform the development of novel therapeutic strategies.
Reference
McAtee CL et al. Genome-wide association study identifies and validates genetic variation in the RIG-I/MAVS signaling pathway associated with HIV-related Kaposi sarcoma in children and adults. Front Oncol. 2026;DOI:10.3389/fonc.2026.1796311.
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