Allostatic load as a potential pathway linking exposomic risk to early-onset cancer: a matched case-control study in the All of Us Research Program

Higher exposomic risk score (ERS) is linked to higher allostatic load (AL) in the All of Us cohort, with β=0.18 SD per SD.

• Why it matters: Early-onset cancer risk models based on single exposures or rare variants may miss cumulative environmental burden, and AL could provide a measurable biological pathway.
• What they did: In a 1:4 matched case-control study (7,550 participants; 1,510 cancers before age 50), ERS from 12 survey measures and an eight-component AL score from EHR data were analyzed with mediation.
• The result: Each SD increase in AL predicted 21% higher odds of early-onset cancer (OR 1.21; 95% CI 1.15–1.28), and AL mediated 17.0% of the ERS–exposome-related EoC association.

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