Abstract 2336: Discovering plasma proteins associated with common solid cancer incidence in ARIC

Background: Plasma proteins, reflecting both exogenous and endogenous factors, could serve as the basis for risk stratification to guide decision-making for primary and secondary prevention of cancer in adults. Published studies have investigated the prospective risk of cancers and other chronic diseases associated with Olink-based proteomic data available in the UK Biobank Study. There is a need for further investigations based on alternative measurement platforms, longer follow-up data, and diverse populations. Aim: Identify proteins measured by SomaScan assay® 5K that are associated with risk of solid cancers in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort of middle-aged and older Black and White men and women. Methods: The study was conducted based on a cohort of 9,495 individuals for which a total of 590, 416, 22, 97, 271, 88, 136 incident cancers of prostate, lung, liver, kidney, colorectal, pancreatic, and bladder were observed over a maximum follow-up period of 25.9 years. Log2-transformed relative fluorescence unit of 4,955 SOMAmers measured in plasma collected at Visit 2 were adjusted in a linear regression model including proteomic PEER factors, study sites, and ten genetic principal components (PCs). Corrected protein quantifications based on rank-inverse normalization of the residuals were used in the analysis. Incident cancers were ascertained primarily by cancer registry linkage. The Cox regression model and time-dependent coefficient Cox model for age at Visit 2 were applied to estimate associations between individual proteins and each solid cancer risk, adjusting for potential environmental risk factors, race, genetic PCs, and PEER factors. Sensitivity analyses examined associations with extended lag-time (diagnosis more than 5 years after Visit 2) and minimally adjusted Cox model for cancer risk. Results: We identified 32 proteins (19 positively, 13 inversely) for liver cancer risk, 5 proteins (4 positively, 1 inversely) for lung cancer risk in both main and sensitivity analyses at false discovery rate (FDR) <0.05. 2 known proteins (MMP7 and HAVCR1) were identified to be positively associated with kidney cancer, and 2 (ACP3 and KLK3) were identified for prostate cancer. We further identified GSTM1 associated with bladder cancer risk [HR (95% CI): 0.68 (0.56, 0.82)] and found evidence of enrichment of signals for proteomics association with colorectal cancer at nominal threshold P < 0.05 (371 proteins for colorectal cancer, 401 proteins for colon cancer only, and 425 proteins for rectal cancer). Conclusion: We discovered multiple circulating proteins associated with lung and liver cancer risks, and confirmed previously established circulating proteins for kidney and prostate cancer risks. Additional evaluations in independent and large cohort studies and laboratory testing will be necessary to validate our results. Support: NHGRI, NHLBI, NCI, NPCR. Citation Format: Ziqiao Wang, Vernon A. Burk, Nilanjan Chatterjee, Elizabeth Platz. Discovering plasma proteins associated with common solid cancer incidence in ARIC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2336.