Abstract 2225: A composite smoking-related plasma protein score is associated with smoking-related cancer risk and mortality beyond self-reported smoking history in Atherosclerosis Risk in Communities Study (ARIC)
Authors: Ru Meng , Douville Christopher , Ballantyne Christie M. , Butler Kenneth R. , Coresh Josef , Couper David J. , Hoogeveen Ron C. , Joshu Corinne E. , Lu Jiayun , Marrone Michael T. , Prizment Anna E. , Tin Adrienne , Platz Elizabeth A. 
Published: June 2022

Abstract
Background: Cigarette smoking is a leading causal risk factor for 13 cancers. Widely used self-reported smoking/packyears may not fully capture individualized risk of smoking-related cancer. Biomarkers (e.g., smoking-related proteins) may reflect biological effect of smoking and refine risk for personalized cancer screening recommendation.
Methods: Protein levels were measured by SomaScan assay (log2 transformed) in Visit 3 plasma from ARIC. Participants were divided 50/50 into set-1 for protein selection and score building and set-2 for association analyses. In set-1, protein levels were evaluated in association with smoking status, packyears smoked, and time since quitting using linear regression. Proteins that passed the Bonferroni threshold were screened with elastic net regression to address correlation. For positively-related proteins, those with levels ≥median were assigned the weight of 1. For inversely-related proteins, those 3 yrs ago, former-quit&lt;3 yrs ago, never) and packyears.
Results: 9901 participants without a prior cancer history were included (46% male, mean age=60 yr, median follow-up=20.1 yr). In set-1, we selected 36, 46, 4 (65 unique) proteins related to current smoker, former-quit&lt;3 yrs ago, packyears, respectively. In set-2, we ascertained 589 and 381 smoking-associated cancer cases and deaths, respectively. Median score was 31 (IQR: 12). The aHRs for smoking-related cancer incidence and mortality (Q4 vs Q1) were 2.35 (95% CI 1.83-3.02, p-trend&lt;0.001) and 2.96 (2.12-4.14; p-trend&lt;0.001) before adjusting for smoking, and 1.28 (0.96-1.70; p-trend=0.06) and 1.52 (1.04-2.22; p-trend=0.04) after adjusting for smoking. The aHRs for lung cancer were 6.81 (4.11-11.28), 6.84 (3.82-12.24), 2.02 (1.15-3.55) and 2.08 (1.09-3.95), respectively (all p-trend≤0.03).
Conclusions: We showed that a preliminary, protein-derived composite score provides relative risk information beyond known cancer risk factors and self-reported smoking. Use of such a score may provide value for refining individualized risk for smoking-associated cancers and may guide precision screening.
Funding: NHLBI, NCI, NPCR.
Citation Format: Meng Ru, Christopher Douville, Christie M. Ballantyne, Kenneth R. Butler, Josef Coresh, David J. Couper, Ron C. Hoogeveen, Corinne E. Joshu, Jiayun Lu, Michael T. Marrone, Anna E. Prizment, Adrienne Tin, Elizabeth A. Platz. A composite smoking-related plasma protein score is associated with smoking-related cancer risk and mortality beyond self-reported smoking history in Atherosclerosis Risk in Communities Study (ARIC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2225.