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Preprints.org
By López-López JA, Cabrera-Serrano AJ, Carretero-Fernández M and 12 others.
Autophagy maintains cellular homeostasis and has context-dependent roles in prostate cancer (PCa). We investigated whether common variation in autophagy-related genes influences PCa susceptibility.
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We meta-analyzed UK Biobank and FinnGen genome-wide association study (GWAS) datasets, including 17,583 cases and 279,188 controls. Among 50,020 shared variants, 16 were prioritized, and 13 were evaluated in a Spanish cohort (218 cases and 468 controls). Functional analyses were conducted in two Human Functional Genomics Project (HFGP) cohorts (500FG and 300OB) and complemented by in silico molecular quantitative trait locus (QTL) analyses.
In the overall meta-analysis, TNFSF10-rs7631904 showed the strongest association (OR = 1.07, P = 4.92×10-7). ARNT-rs72992015 was associated with PCa risk in Spain (OR = 2.09, P = 5.55×10-3) and overall (OR = 1.07, P = 2.80×10-6), with between-cohort heterogeneity (Phet = 0.01). ARNT-rs72992015 was associated with circulating VEGF concentrations in healthy participants (P = 7.86×10-4) and TNFSF10-rs7631904 was associated with the monocyte-to-lymphocyte ratio (P = 8.81×10-4), circulating EN-RAGE (P = 2.85×10-3), and cathepsin L concentrations (P = 8.34×10-3) in obese participants. Prostate eQTL analyses linked VAMP3, ARNT and MAP1LC3A variants to VAMP3, CTSS and MAP1LC3A expression, respectively.
These findings identify autophagy-related susceptibility signals with exploratory immune, inflammatory, and regulatory associations. Genetic replication, colocalization analyses, and experimental validation are needed to establish their functional relevance.
This is a preprint: it has not been peer reviewed yet, and its findings may change.
Published in Preprints.org (preprint). The abstract is shown as published and remains the work of its authors; read the full article at the source.
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