1.
Association of Adiponectin and Vitamin D With Tumor Infiltrating Lymphocytes and Survival in Stage III Colon Cancer.
Sinicrope, FA, Shi, Q, Smyrk, TC, Goldberg, RM, Cohen, SJ, Gill, S, Kahlenberg, MS, Nair, S, Shield, AF, Jahagirdar, BN, et al
JNCI cancer spectrum. 2021;(5)
Abstract
BACKGROUND Adipocyte-derived adiponectin may play a role in the host inflammatory response to cancer. We examined the association of plasma adiponectin with the density of tumor-infiltrating lymphocytes (TILs) in colon cancers and with vitamin D, clinicopathological features, and patient survival. METHODS Plasma adiponectin and 25-hydroxyvitamin D [25(OH)D] were analyzed by radioimmunoassay in 600 patients with stage III colon cancer who received FOLFOX-based adjuvant chemotherapy (NCCTG N0147 [Alliance]). TIL densities were determined in histopathological sections. Associations with disease-free survival (DFS), time to recurrence, and overall survival were evaluated by multivariable Cox regression adjusting for potential confounders (ie, body mass index, race, TILs, and N stage). All statistical tests were 2-sided. RESULTS We found a statistically significant reduction in adiponectin, but not 25(OH)D, levels in tumors with high vs low TIL densities (median = 6845 vs 8984 ng/mL; P = .04). A statistically significant reduction in adiponectin was also observed in obese (body mass index >30 kg/m2) vs nonobese patients (median = 6608 vs 12 351 ng/mL; P < .001), in men vs women (median = 8185 vs 11 567 ng/mL; P < .001), in Blacks vs Whites or Asians (median = 6412 vs 8847 vs 7858 ng/mL; P < .03), and in those with fewer lymph node metastases (N1 vs N2: median = 7768 vs 9253 ng/mL; P = .01). Insufficiency of 25(OH)D (<30 ng/mL) was detected in 291 (48.5%) patients. In multivariable analyses, neither adiponectin nor 25(OH)D were associated with a statistically significant difference in DFS, overall survival , or time to recurrence in models adjusted for potential confounders. We found a statistically significant association of TILs with prognosis, yet no such interaction was observed for the association of adiponectin with TILs for DFS. CONCLUSIONS Lower circulating adiponectin levels were associated with a statistically significant increase in TIL densities in colon cancers, indicating an enhanced antitumor immune response. In contrast to TILs, neither adiponectin nor 25(OH)D was independently prognostic.
2.
Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development.
Pietrzyk, L, Torres, A, Maciejewski, R, Torres, K
Asian Pacific journal of cancer prevention : APJCP. 2015;(10):4161-8
Abstract
Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-α (TNF-α). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).