Abstract 3428: Association of adipokines and inflammation biomarkers with cancer risk in men
Authors: Douglas DeMoulin, Hui Cai, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu
Journal: Cancer Research (2024)

Abstract Using pre-diagnosis fasting plasma samples from 4,040 participants of the Shanghai Men’s Health Study which enrolled 61,464 men ages 40-70 during 2001-2006, we prospectively evaluated the associations of adipokines and inflammation biomarkers with cancer risk. Levels of leptin, resistin, adiponectin, plasminogen activator inhibitor type-1 (PAI-1), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNFa), monocyte chemoattractant protein-1 (MCP-1), and insulin were measured by Luminex assays, and C-reactive protein (CRP), measured by ACE Clinical Chemistry System. Biomarker levels were categorized by tertile distribution. The Cox regression model was applied to derive hazard ratios (HR) and 95% confidence intervals (CI) for cancer risk in association with biomarkers with adjustment for potential confounders. Principle component analysis (PCA) was performed to assess associations with multiple biomarkers, and tertile scores for each component were used in analyses. During 15-years of follow-up, 318 cancer cases were identified, including 85 lung, 49 gastric, 17 liver, and 61 colorectal cancer (CRC) cases. Analyses adjusted for age, education and income showed that 3rd vs 1st tertile of TNFa (HR=1.7, 95%CI=1.0-3.0) and adiponectin (HR=4.0, 95%CI=1.1-14.4) was associated with lung and liver cancer risk, respectively. High levels of leptin, insulin, and CRP were each associated with CRC risk: respective HRs were 2.3 (95%CI=1.1-4.7), 2.1 (95%CI=1.0-4.2), and 2.0 (95%CI=1.1-3.9). After further adjustment for known cancer risk factors, TNFa-lung cancer (HR=1.8, 95%CI=1.1-3.1); leptin-CRC (HR= 3.2, 95%CI=1.3-7.7); insulin-CRC (HR=2.1, 95%CI=1.0-4.5); and CRP-CRC (HR=2.0, 95%CI=1.0-4.0) associations remained statistically significant. The adiponectin-lung cancer association lost significance. PCA identified 4 principal components (PC). High PC1 score (main loadings: TNFa, leptin, and insulin) was associated with CRC risk (HR=2.3, 95%CI=1.1-5.0 for 3rd vs 1st tertile ptrend=0.02). High PC2 score (main loadings: adiponectin, IL-8, MCP-1) and PC3 (main loadings: resistin and PAI-1) were associated with liver cancer risk: HR=5.2 (95%CI=1.1-24.3) for the 3rd vs 1st tertile, ptrend=0.03 and HR=4.7 (95%CI=1.0-21.7), for the 3rd vs 1st tertile, ptrend=0.03, respectively. High PC4 score (main loadings: IL-6 and CRP) was associated with lung cancer risk (HR=1.7, 95%CI=1.0-3.0, for the 3rd vs 1st tertile, ptrend=0.04). These associations, except the PC1-CRC association, lost significance after further adjustment of known cancer risk factors. Our study found that high plasma levels of insulin, CRP, and their combination were associated with CRC risk, high resistin and adiponectin levels with liver cancer risk, and high TNFa levels with lung cancer risk. Some biomarker-cancer associations may be explained by their correlations with known cancer risk factors, especially smoking. Citation Format: Douglas DeMoulin, Hui Cai, Qiuyin Cai, Wei Zheng, Xiao-Ou Shu. Association of adipokines and inflammation biomarkers with cancer risk in men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3428.