Mechanistic insights into cancer risk from the circulating proteome

This dataset contains all aptamer-cancer associations for incident and prevalent cancers in the AGES study as described in the manuscript "Mechanistic insights into cancer risk from the circulating proteome". Abstract Background Early cancer detection could substantially improve patient survival and reduce disease burden. Ideally, such advances would be enabled by minimally invasive, cancer-type-specific biomarkers that also illuminate mechanisms of tumorigenesis. Proteogenomic studies of circulating proteins can reveal novel biomarker candidates and inform on causal pathways driving cancer risk. Methods and findings We examined associations between 7,521 serum protein measurements and 13 cancer types in 5,323 participants from the prospective, population-based Age, Gene/Environment Susceptibility (AGES) Reykjavik cohort (recruitment 2002 - 2006), including 465 prevalent and 770 incident cancer cases during a follow-up of up an average of 10 years, spanning digestive, genitourinary, respiratory, female reproductive, and skin cancers. After adjusting for confounders and considering sex-specific effects, we identified 544 unique serum proteins significantly associated with incident and/or prevalent cancers. Applying proteome-wide two-sample Mendelian randomization together with colocalization analysis, we prioritize 48 proteins with potentially causal roles in cancer development. By integrating our findings with cancer-associated genes, tissue- and tumor-specific expression profiles, oncogene and tumor suppressor annotations, we identified distinct patterns of protein involvement that highlight the complex, cancer-specific molecular architecture of malignancy. Conclusions Our findings demonstrate the potential of circulating proteomics for population-level cancer surveillance, early detection, and mechanistic insights into cancer etiology.