Associations of Human Colorectal Adenoma with Serum Biomarkers of Body Iron Stores, Inflammation and Antioxidant Protein Thiols

Red and processed meat consumption and obesity are established risk factors for colorectal adenoma (CRA). Adverse changes in biomarkers of body iron stores (total serum iron, ferritin, transferrin and transferrin saturation), inflammation (high-sensitivity C-reactive protein [hs-CRP]) and anti-oxidative capacity (total of thiol groups (-S-H) of proteins [SHP]) might reflect underlying mechanisms that could explain the association of red/processed meat consumption and obesity with CRA. Overall, 100 CRA cases (including 71 advanced cases) and 100 CRA-free controls were frequency-matched on age and sex and were selected from a colonoscopy screening cohort. Odds ratios (OR) and 95% confidence intervals (95%CI) for comparisons of top and bottom biomarker tertiles were derived from multivariable logistic regression models. Ferritin levels were significantly positively associated with red/processed meat consumption and hs-CRP levels with obesity. SHP levels were significantly inversely associated with obesity. Transferrin saturation was strongly positively associated with overall and advanced CRA (ORs [95%CIs]: 3.05 [1.30–7.19] and 2.71 [1.03–7.13], respectively). Due to the high correlation with transferrin saturation, results for total serum iron concentration were similar (but not statistically significant). Furthermore, SHP concentration was significantly inversely associated with advanced CRA (OR [95%CI]: 0.29 [0.10–0.84]) but not with overall CRA (OR [95%CI]: 0.65 [0.27–1.56]). Ferritin, transferrin, and hs-CRP levels were not associated with CRA. High transferrin saturation as a sign of iron overload and a low SHP concentration as a sign of redox imbalance in obese patients might reflect underlying mechanisms that could in part explain the associations of iron overload and obesity with CRA.

[1]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[2]  L. Milković,et al.  The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies , 2020, Antioxidants.

[3]  H. Brenner,et al.  Factors associated with high oxidative stress in patients with type 2 diabetes: a meta-analysis of two cohort studies , 2020, BMJ Open Diabetes Research & Care.

[4]  H. Brenner,et al.  Longitudinal Associations of Body Mass Index, Waist Circumference, and Waist-to-Hip Ratio with Biomarkers of Oxidative Stress in Older Adults: Results of a Large Cohort Study , 2020, Obesity Facts.

[5]  L. Milković,et al.  The relevance of pathophysiological alterations in redox signaling of 4-hydroxynonenal for pharmacological therapies of major stress-associated diseases. , 2019, Free radical biology & medicine.

[6]  H. Brenner,et al.  Pre‐diagnostic derivatives of reactive oxygen metabolites and the occurrence of lung, colorectal, breast and prostate cancer: An individual participant data meta‐analysis of two large population‐based studies , 2019, International journal of cancer.

[7]  H. Brenner,et al.  Investigation on potential associations of oxidatively generated DNA/RNA damage with lung, colorectal, breast, prostate and total cancer incidence , 2019, Scientific Reports.

[8]  N. Žarković,et al.  The Role of Acrolein and NADPH Oxidase in the Granulocyte-Mediated Growth-Inhibition of Tumor Cells , 2019, Cells.

[9]  D. Melzer,et al.  Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank , 2019, British Medical Journal.

[10]  D. Bernlohr,et al.  Adipose oxidative stress and protein carbonylation , 2018, The Journal of Biological Chemistry.

[11]  G. Frühbeck,et al.  NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development , 2018, Front. Immunol..

[12]  H. Brenner,et al.  The colorectal cancer epidemic: challenges and opportunities for primary, secondary and tertiary prevention , 2018, British Journal of Cancer.

[13]  N. Žarković,et al.  4-Hydroxynonenal in Redox Homeostasis of Gastrointestinal Mucosa: Implications for the Stomach in Health and Diseases , 2018, Antioxidants.

[14]  H. Brenner,et al.  Urinary 8‐isoprostane levels and occurrence of lung, colorectal, prostate, breast and overall cancer: Results from a large, population‐based cohort study with 14 years of follow‐up , 2018, Free radical biology & medicine.

[15]  E. Jansen,et al.  Long-term stability of oxidative stress biomarkers in human serum , 2017, Free radical research.

[16]  R. Bostick,et al.  A Novel Application of Structural Equation Modeling Estimates the Association between Oxidative Stress and Colorectal Adenoma , 2017, Cancer Prevention Research.

[17]  L. Milković,et al.  Cancer growth regulation by 4‐hydroxynonenal , 2017, Free radical biology & medicine.

[18]  S. Tu,et al.  Iron intake, serum iron indices and risk of colorectal adenomas: a meta‐analysis of observational studies , 2017, European journal of cancer care.

[19]  D. Albanes,et al.  Serum ghrelin is associated with risk of colorectal adenocarcinomas in the ATBC study , 2017, Gut.

[20]  B. Schöttker,et al.  Reduction-oxidation pathways involved in cancer development: a systematic review of literature reviews. , 2017, Oncotarget.

[21]  E. Giovannucci,et al.  Markers of systemic inflammation and colorectal adenoma risk: Meta-analysis of observational studies , 2017, World journal of gastroenterology.

[22]  R. Olszanecki,et al.  Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats , 2016, International journal of molecular sciences.

[23]  M. Nakazato,et al.  Ghrelin administration suppresses inflammation-associated colorectal carcinogenesis in mice , 2015, Cancer science.

[24]  Z. Warzecha,et al.  Peptidyl hormones of endocrine cells origin in the gut--their discovery and physiological relevance. , 2015, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[25]  R. Sinha,et al.  Meat , dairy , and cancer 1 – 4 , 2014 .

[26]  R. Bostick,et al.  Oxidative Balance Score, Colorectal Adenoma, and Markers of Oxidative Stress and Inflammation , 2014, Cancer Epidemiology, Biomarkers & Prevention.

[27]  Rafael Radi,et al.  The thiol pool in human plasma: the central contribution of albumin to redox processes. , 2013, Free radical biology & medicine.

[28]  A. Agudo,et al.  Iron and Cancer Risk—A Systematic Review and Meta-analysis of the Epidemiological Evidence , 2013, Cancer Epidemiology, Biomarkers & Prevention.

[29]  Michael J Blaha,et al.  High-sensitivity C-reactive protein and cardiovascular disease: a resolute belief or an elusive link? , 2013, Journal of the American College of Cardiology.

[30]  R. Xu,et al.  A Brief Review of the Controversial Role of Iron in Colorectal Carcinogenesis , 2013 .

[31]  A. Munshi,et al.  C-Reactive Protein and Nitric Oxide Levels in Ischemic Stroke and Its Subtypes: Correlation with Clinical Outcome , 2012, Inflammation.

[32]  R. Sinha,et al.  Iron Homeostasis and Distal Colorectal Adenoma Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial , 2011, Cancer Prevention Research.

[33]  R. Lau,et al.  Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies , 2011, PloS one.

[34]  G. Baldwin,et al.  Gastrins, iron homeostasis and colorectal cancer. , 2011, Biochimica et biophysica acta.

[35]  B. Tudek,et al.  Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients. , 2010, Mutagenesis.

[36]  H. Brenner,et al.  Comparative Evaluation of Immunochemical Fecal Occult Blood Tests for Colorectal Adenoma Detection , 2009, Annals of Internal Medicine.

[37]  Kelly A. Smith,et al.  Interrelationships between circulating gastrin and iron status in mice and humans. , 2008, American journal of physiology. Gastrointestinal and liver physiology.

[38]  M. Fonseca-Alaniz,et al.  Adipose tissue as an endocrine organ: from theory to practice. , 2007, Jornal de pediatria.

[39]  G. Hotamisligil,et al.  Inflammation and metabolic disorders , 2006, Nature.

[40]  Dean P. Jones.  Redefining oxidative stress. , 2006, Antioxidants & redox signaling.

[41]  Marco Guarneri,et al.  Relation of C-reactive protein to oxidative stress and to endothelial activation in essential hypertension. , 2006, American journal of hypertension.

[42]  N. Žarković,et al.  Tissue distribution of lipid peroxidation product acrolein in human colon carcinogenesis , 2006, Free radical research.

[43]  D. Hunter,et al.  Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women. , 2005, Journal of the National Cancer Institute.

[44]  M. Korbonits,et al.  Ghrelin—a hormone with multiple functions , 2004, Frontiers in Neuroendocrinology.

[45]  S. Bingham,et al.  Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. , 2003, Cancer research.

[46]  J. Delanghe,et al.  Total Iron Binding Capacity and Transferrin Concentration in the Assessment of Iron Status , 2002, Clinical chemistry and laboratory medicine.

[47]  S. Kelly,et al.  Plasma levels of progastrin but not amidated gastrin or glycine extended gastrin are elevated in patients with colorectal carcinoma , 2000, Gut.

[48]  S. Toyokuni,et al.  Persistent oxidative stress in human colorectal carcinoma, but not in adenoma. , 1999, Free radical biology & medicine.

[49]  L. Hallberg,et al.  Iron absorption from the whole diet in men: how effective is the regulation of iron absorption? , 1997, The American journal of clinical nutrition.

[50]  C. L. Bird,et al.  Plasma ferritin, iron intake, and the risk of colorectal polyps. , 1996, American journal of epidemiology.

[51]  F. Davis,et al.  Body iron stores and risk of colonic neoplasia. , 1994, Journal of the National Cancer Institute.

[52]  P. Schrotz-King,et al.  Direct Comparison of Diagnostic Performance of 9 Quantitative Fecal Immunochemical Tests for Colorectal Cancer Screening. , 2018, Gastroenterology.

[53]  M. Bissell.  Low-Dose Aspirin Use and Performance of Immunochemical Fecal Occult Blood Tests , 2012 .

[54]  Z. Warzecha,et al.  Protective and therapeutic effects of ghrelin in the gut. , 2012, Current medicinal chemistry.

[55]  J. Hardcastle,et al.  Colorectal cancer , 1993, Europe Against Cancer European Commission Series for General Practitioners.