Table 1.

Associations between “Cancer Risk”, “Inflammation”, and “Metabolic Syndrome” in cancer.

Author(s) Publication Year Level of Evidence	Oncogenesis or Cancer Typology	Biomarkers Assessed	Conditions Assessed	Findings
Jee et al., 2005 [24] level I	Cervix Colon/Rectum Breast Esophagus Leukemia Liver Pancreas Stomach	AP-1 CRP FFA IGFBP3 IGF1 IL-6 IL-1β Insulin MCP-1 MMP-9 NF-κB PAI-1 TF TNF-α	Central obesity Dyslipidemia, hyperglycemia Hypertension	A high BMI increased the risk of colon cancer but was not associated with rectal cancer. Triglyceride levels in the blood did not increase the risk of colorectal cancer.
Sumantran and Tillu 2012 [25] level I	Oncogenesis	Ama COX-2 HIF-1 alpha IL-6 iNOS MCP-1 NF-κB NO OLR-1 PPARs Prostaglandins STAT-3 TNF-α	Abnormal lipid metabolism Chronic inflammation Diet Obesity T2DM	Tumor-infiltrating leukocytes and TAMs were recognized in the tumor stroma. The inflammatory microenvironment directly improved tumor progression, evasion, of apoptosis, and accelerated the processes of angiogenesis, invasion, and metastasis.
Gristina et al., 2015 [20] level I	CRC HCC	C-Reactive IGF1 IL-6 PI3K TNF-α	BMI Hyperinsulinemia Obesity T2DM	T2DM and MetS were directly associated to obesity-related hyperinsulinemia and increasing levels of IGF-1. These mechanisms were considered as key factors in carcinogenesis.
Veniou et al., 2016 [27] level I	Bladder Breast Colon Colorectal Endometrium Gastric HCC Lung Ovary Pancreas Prostate Rectal Thyroid	Adiponectin AMPK IGF-1 IGFBP-3 IR HDLc Leptin mTOR Triglycerides	Aromatase BMI Cytotoxic products inducing insulin resistance Dysglycemia Hyperinsulinemia Hypertension Inflammation MetS Obesity	Insulin stimulated the production of IGF-1 by upregulating the GH receptors in the liver. Activation of IGF-1R stimulated cell proliferation through RAS/MAPK signaling pathway with anti-apoptotic consequence via the PI3K/AKT pathway. Among patients with wild-type RAS cancers, the prognosis was dismal in the obese subgroup.
Battelli et al., 2019 [28] level I	Oncogenesis	COX-2 HIF-1α Insulin LDL NF-kβ NO ROS Uric Acid VEGF XOR	Inflammation MetS Oncogenesis Oxidative stress T2DM	XOR was involved in the pathogenesis of both MetS and cancer through the inflammatory response and the oxidative stress. ROS and nitrogen species and the uric acid derived from XOR improved hypertension, dyslipidemia and insulin resistance, participating in cell transformation and proliferation and also in the progression and metastasis process.
Yu et al., 2020 [29] level I	General	GDH1 K-ras mTOR MAPK MYC P53 Statins TNF-α	Cell signaling pathways Chronic inflammation Dyslipidemia Hyperglycemia Inflammation MetS Obesity Oxidative stress ROS	Increased ROS production, chronic inflammation, and aberrant activation of oncogenic signaling pathways represent important links between metabolic disorders and cancer.
Neshat et al., 2022 [30] level I	Breast Cervical Colon Endometrial Epithelial Esophageal General Gastric Hematological Liver Lung Ovarian Prostate	HDL-C LDL-C Statins TG	CVD Dyslipidemia Hypercholesterolemia	Cholesterol, HDL-C, LDL-C, and TG levels and statins could positively impact on the incidence, progression, and prognosis of different types of cancer, such as lung, prostate, ovary, breast, and gastrointestinal cancers.
Sergeeva et al., 2023 [31] level I	Adrenocortical Breast Colon CRC Endometrium Esophageal HCC Melanoma	Estrogens HbA1c IGFBP IGFBPL1 MAPK mTOR PI3K	Chronic inflammation Hyperinsulinemia Hypoxia Inflammation Lipid metabolism Obesity Oxidative stress	Obesity and cancer development was based on several alterations of metabolism. Increased levels of glucose, fructose, and lipids could be linked to increased food uptake with altered expression of factors regulating metabolic processes under obesity. Obesity was associated with IGF axis alterations and increased estrogen levels. Low-grade chronic inflammation, deregulation of adipokines levels, and hypoxia associated to obesity were very important in cancer genesis and its progression.
Pandit et al., 2024 [32] level I	CRC General	AMPK FFAs HER2 Hsp90 IGFs IL-1 IL-6 IL-8 NF-kβ STAT3 TNF-α	BMI Leptins STA-3-mediated	Higher BMI scores was associated to increased risks of malignancies.

Abbreviations: AMPK: adenosine monophosphate-activated protein kinase is an enzyme; AP-1: activating protein-1; COX-2: cyclooxygenase-2; CRC: colorectal cancer; CRP: C-reactive protein; CVD: cardiovascular disease; GDH1: glutamate dehydrogenase; HbA1C: glycated hemoglobin; HCC: hepatocellular carcinoma; HDL-C: total cholesterol, high-density lipoprotein cholesterol; HER2: human epidermal growth factor receptor 2; HIF-1 alpha: hypoxia-inducible factor 1alpha; Hsp90: heat shock protein; IGF-1: insulin-like growth factor-1; IGFBP3: insulin-like growth factor binding protein; IL-6: interleukine-6; iNOS: inducible nitric oxide synthase; IR: insulin receptor; LDL-C: low-density lipoprotein cholesterol; MCP-1: monocyte chemotactic protein-1; MMP-9: matrix metalloproteinase-9; mTOR: mechanistic target of rapamycin; NF-κB: factor-kappa B; NO: nitric oxide; OLR-1: oxidized LDL receptor 1, PAI-1: plasminogen activator inhibitor-1; PI3K: phosphoinositide 3-kinase; PPARs: peroxisome proliferator-activated receptors; ROS: reactive oxygen species; STAT: signal transducer and activator of transcription; TF: tissue factor; TG: triglyceride; T2DM: type 2 diabetes mellitus; VEGF, vascular endothelial growth factor; XOR: xanthine oxidoreductase.