Skip to main content
Top
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma

Authors: Curtis J Henry, Rebecca L Sedjo, Andrii Rozhok, Jennifer Salstrom, Dennis Ahnen, Theodore R Levin, Ralph D’Agostino Jr, Steven Haffner, James DeGregori, Tim Byers

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear.

Methods

Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin-10 (IL-10), IL-1β, IL-6, IL-17A, IL-2, IL-4, IL-7, IL-12(p70), interferon-γ (IFN-γ), macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1β (MIP-1β) were determined. Multiple logistic regression analyses were used to evaluate the association between adenoma prevalence and cytokine levels.

Results

The presence of colorectal adenomas was not associated with significant increases in the systemic levels of proinflammatory (TNF-α, IL-6, IL-1β) or T-cell polarizing (IL-12, IL-2, IL-10, IL-4, IL-17, IFN-γ) cytokines. Furthermore, MCP-1 and RANTES levels were equivalent in the serum of study participants with and without adenomas.

Conclusions

These findings suggest colorectal adenoma prevalence may not be associated with significant alterations in systemic inflammation.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.CrossRefPubMed
2.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;6(2):69–90.CrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;6(2):69–90.CrossRef
3.
go back to reference Kang M, Edmundson P, Araujo-Perez F, McCoy AN, Galanko J, Keku TO. Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas. BMC Cancer. 2013;13:91.CrossRefPubMedPubMedCentral Kang M, Edmundson P, Araujo-Perez F, McCoy AN, Galanko J, Keku TO. Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas. BMC Cancer. 2013;13:91.CrossRefPubMedPubMedCentral
4.
go back to reference Olsen HW, Lawrence WA, Snook CW, Mutch WM. Risk factors and screening techniques in 500 patients with benign and malignant colon polyps. An urban community experience. Dis Colon Rectum. 1988;31(3):216–21.CrossRefPubMed Olsen HW, Lawrence WA, Snook CW, Mutch WM. Risk factors and screening techniques in 500 patients with benign and malignant colon polyps. An urban community experience. Dis Colon Rectum. 1988;31(3):216–21.CrossRefPubMed
6.
go back to reference Terzic J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101–14. e5.CrossRefPubMed Terzic J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101–14. e5.CrossRefPubMed
7.
go back to reference Krzystek-Korpacka M, Diakowska D, Kapturkiewicz B, Bebenek M, Gamian A. Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance. Cancer Lett. 2013;337(1):107–14.CrossRefPubMed Krzystek-Korpacka M, Diakowska D, Kapturkiewicz B, Bebenek M, Gamian A. Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance. Cancer Lett. 2013;337(1):107–14.CrossRefPubMed
8.
go back to reference Lakatos L, Mester G, Erdelyi Z, David G, Pandur T, Balogh M, et al. Risk factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: results of a population-based study. Inflamm Bowel Dis. 2006;12(3):205–11.CrossRefPubMed Lakatos L, Mester G, Erdelyi Z, David G, Pandur T, Balogh M, et al. Risk factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: results of a population-based study. Inflamm Bowel Dis. 2006;12(3):205–11.CrossRefPubMed
9.
go back to reference Lee WS, Baek JH, You DH, Nam MJ. Prognostic value of circulating cytokines for stage III colon cancer. J Surg Res. 2013;182(1):49–54.CrossRefPubMed Lee WS, Baek JH, You DH, Nam MJ. Prognostic value of circulating cytokines for stage III colon cancer. J Surg Res. 2013;182(1):49–54.CrossRefPubMed
11.
12.
go back to reference Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology. 1991;101(3):635–9.CrossRefPubMed Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology. 1991;101(3):635–9.CrossRefPubMed
13.
go back to reference Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. 1993;328(18):1313–6.CrossRefPubMed Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. 1993;328(18):1313–6.CrossRefPubMed
14.
go back to reference Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS ONE. 2011;6(1):e16393.CrossRefPubMedPubMedCentral Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS ONE. 2011;6(1):e16393.CrossRefPubMedPubMedCentral
15.
go back to reference Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22(2):292–8.CrossRefPubMedPubMedCentral Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22(2):292–8.CrossRefPubMedPubMedCentral
16.
go back to reference Scanlan PD, Shanahan F, Clune Y, Collins JK, O'Sullivan GC, O'Riordan M, et al. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol. 2008;10(3):789–98.CrossRefPubMed Scanlan PD, Shanahan F, Clune Y, Collins JK, O'Sullivan GC, O'Riordan M, et al. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol. 2008;10(3):789–98.CrossRefPubMed
17.
go back to reference Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. Isme J. 2012;6(2):320–9.CrossRefPubMed Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. Isme J. 2012;6(2):320–9.CrossRefPubMed
18.
go back to reference Guffey CR, Fan D, Singh UP, Murphy EA. Linking obesity to colorectal cancer: recent insights into plausible biological mechanisms. Curr Opin Clin Nutr Metab Care. 2013;16(5):595–600.CrossRefPubMed Guffey CR, Fan D, Singh UP, Murphy EA. Linking obesity to colorectal cancer: recent insights into plausible biological mechanisms. Curr Opin Clin Nutr Metab Care. 2013;16(5):595–600.CrossRefPubMed
19.
go back to reference Huang X, Zou Y, Lian L, Wu X, He X, Huang Y, et al. Changes of T Cells and Cytokines TGF-beta1 and IL-10 in Mice during Liver Metastasis of Colon Carcinoma: Implications for Liver Anti-tumor Immunity. J Gastrointest Surg. 2013;17(7):1283–91.CrossRefPubMed Huang X, Zou Y, Lian L, Wu X, He X, Huang Y, et al. Changes of T Cells and Cytokines TGF-beta1 and IL-10 in Mice during Liver Metastasis of Colon Carcinoma: Implications for Liver Anti-tumor Immunity. J Gastrointest Surg. 2013;17(7):1283–91.CrossRefPubMed
20.
go back to reference Liu Z, Brooks RS, Ciappio ED, Kim SJ, Crott JW, Bennett G, et al. Diet-induced obesity elevates colonic TNF-alpha in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer. J Nutr Biochem. 2012;23(10):1207–13.CrossRefPubMed Liu Z, Brooks RS, Ciappio ED, Kim SJ, Crott JW, Bennett G, et al. Diet-induced obesity elevates colonic TNF-alpha in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer. J Nutr Biochem. 2012;23(10):1207–13.CrossRefPubMed
22.
go back to reference Choi JW, Liu H, Shin DH, Yu GI, Hwang JS, Kim ES, et al. Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients. Proteomics. 2013;13(15):2361–74.CrossRefPubMed Choi JW, Liu H, Shin DH, Yu GI, Hwang JS, Kim ES, et al. Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients. Proteomics. 2013;13(15):2361–74.CrossRefPubMed
23.
go back to reference Wang W, Li X, Zheng D, Zhang D, Huang S, Zhang X, et al. Dynamic changes of peritoneal macrophages and subpopulations during ulcerative colitis to metastasis of colorectal carcinoma in a mouse model. Inflamm Res. 2013;62(7):669–80.CrossRefPubMed Wang W, Li X, Zheng D, Zhang D, Huang S, Zhang X, et al. Dynamic changes of peritoneal macrophages and subpopulations during ulcerative colitis to metastasis of colorectal carcinoma in a mouse model. Inflamm Res. 2013;62(7):669–80.CrossRefPubMed
24.
go back to reference Bobe G, Murphy G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, et al. Serum cytokine concentrations, flavonol intake and colorectal adenoma recurrence in the Polyp Prevention Trial. Br J Cancer. 2010;103(9):1453–61.CrossRefPubMedPubMedCentral Bobe G, Murphy G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, et al. Serum cytokine concentrations, flavonol intake and colorectal adenoma recurrence in the Polyp Prevention Trial. Br J Cancer. 2010;103(9):1453–61.CrossRefPubMedPubMedCentral
25.
go back to reference Bobe G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, Colburn NH, et al. Interleukin-6 as a potential indicator for prevention of high-risk adenoma recurrence by dietary flavonols in the polyp prevention trial. Cancer Prev Res (Phila). 2010;3(6):764–75.CrossRef Bobe G, Albert PS, Sansbury LB, Lanza E, Schatzkin A, Colburn NH, et al. Interleukin-6 as a potential indicator for prevention of high-risk adenoma recurrence by dietary flavonols in the polyp prevention trial. Cancer Prev Res (Phila). 2010;3(6):764–75.CrossRef
26.
go back to reference Chaturvedi AK, Kemp TJ, Pfeiffer RM, Biancotto A, Williams M, Munuo S, et al. Evaluation of multiplexed cytokine and inflammation marker measurements: a methodologic study. Cancer Epidemiol Biomarkers Prev. 2011;20(9):1902–11.CrossRefPubMedPubMedCentral Chaturvedi AK, Kemp TJ, Pfeiffer RM, Biancotto A, Williams M, Munuo S, et al. Evaluation of multiplexed cytokine and inflammation marker measurements: a methodologic study. Cancer Epidemiol Biomarkers Prev. 2011;20(9):1902–11.CrossRefPubMedPubMedCentral
27.
go back to reference Parkitny L, McAuley JH, Kelly PJ, Di Pietro F, Cameron B, Moseley GL. Multiplex cytokine concentration measurement: how much do the medium and handling matter? Mediators Inflamm. 2013;2013:1–13. Article ID 890706.CrossRef Parkitny L, McAuley JH, Kelly PJ, Di Pietro F, Cameron B, Moseley GL. Multiplex cytokine concentration measurement: how much do the medium and handling matter? Mediators Inflamm. 2013;2013:1–13. Article ID 890706.CrossRef
28.
go back to reference Wagenknecht LE, Mayer EJ, Rewers M, Haffner S, Selby J, Borok GM, et al. The insulin resistance atherosclerosis study (IRAS) objectives, design, and recruitment results. Ann Epidemiol. 1995;5(6):464–72.CrossRefPubMed Wagenknecht LE, Mayer EJ, Rewers M, Haffner S, Selby J, Borok GM, et al. The insulin resistance atherosclerosis study (IRAS) objectives, design, and recruitment results. Ann Epidemiol. 1995;5(6):464–72.CrossRefPubMed
29.
go back to reference Sedjo RL, Byers T, Levin TR, Haffner SM, Saad MF, Tooze JA, et al. Change in body size and the risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 2007;16(3):526–31.CrossRefPubMed Sedjo RL, Byers T, Levin TR, Haffner SM, Saad MF, Tooze JA, et al. Change in body size and the risk of colorectal adenomas. Cancer Epidemiol Biomarkers Prev. 2007;16(3):526–31.CrossRefPubMed
30.
go back to reference Diabetes mellitus. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1985;727:1–113. Diabetes mellitus. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1985;727:1–113.
31.
go back to reference Lee SK, Surh CD. Role of interleukin-7 in bone and T-cell homeostasis. Immunol Rev. 2005;208:169–80.CrossRefPubMed Lee SK, Surh CD. Role of interleukin-7 in bone and T-cell homeostasis. Immunol Rev. 2005;208:169–80.CrossRefPubMed
32.
go back to reference D’Agostiono RB. Transformation to normality of the null distribution of g 1 . Biometrika. 1970;57(3):679–81. D’Agostiono RB. Transformation to normality of the null distribution of g 1 . Biometrika. 1970;57(3):679–81.
33.
go back to reference D’Agostino RB, Belanger A, D’Agostino Jr RB. A suggestion for using powerful and informative tests of normality. Am Stat. 1990;44(4):316–21. D’Agostino RB, Belanger A, D’Agostino Jr RB. A suggestion for using powerful and informative tests of normality. Am Stat. 1990;44(4):316–21.
34.
go back to reference Navarrete-Reyes AP, Montana-Alvarez M. Inflammaging, Aging inflammatory origin. Rev Invest Clin. 2009;61(4):327–36.PubMed Navarrete-Reyes AP, Montana-Alvarez M. Inflammaging, Aging inflammatory origin. Rev Invest Clin. 2009;61(4):327–36.PubMed
35.
go back to reference Rotondi M, Chiovato L. The chemokine system as a therapeutic target in autoimmune thyroid diseases: a focus on the interferon-gamma inducible chemokines and their receptor. Curr Pharm Des. 2011;17(29):3202–16.CrossRefPubMed Rotondi M, Chiovato L. The chemokine system as a therapeutic target in autoimmune thyroid diseases: a focus on the interferon-gamma inducible chemokines and their receptor. Curr Pharm Des. 2011;17(29):3202–16.CrossRefPubMed
36.
go back to reference Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003;3(2):133–46.CrossRefPubMed Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003;3(2):133–46.CrossRefPubMed
37.
go back to reference O'Garra A, Murphy KM. From IL-10 to IL-12: how pathogens and their products stimulate APCs to induce T(H)1 development. Nat Immunol. 2009;10(9):929–32.CrossRefPubMed O'Garra A, Murphy KM. From IL-10 to IL-12: how pathogens and their products stimulate APCs to induce T(H)1 development. Nat Immunol. 2009;10(9):929–32.CrossRefPubMed
38.
go back to reference Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res. 2008;68(1):323–8.CrossRefPubMedPubMedCentral Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res. 2008;68(1):323–8.CrossRefPubMedPubMedCentral
39.
go back to reference Half E, Arber N. Colon cancer: preventive agents and the present status of chemoprevention. Expert Opin Pharmacother. 2009;10(2):211–9.CrossRefPubMed Half E, Arber N. Colon cancer: preventive agents and the present status of chemoprevention. Expert Opin Pharmacother. 2009;10(2):211–9.CrossRefPubMed
40.
go back to reference Huang WK, Chiou MJ, Yu KH, Lin YC, Yang TS, Chen JS, et al. The association between low-dose aspirin use and the incidence of colorectal cancer: a nationwide cohort study. Aliment Pharmacol Ther. 2013;38(4):432–9.CrossRefPubMed Huang WK, Chiou MJ, Yu KH, Lin YC, Yang TS, Chen JS, et al. The association between low-dose aspirin use and the incidence of colorectal cancer: a nationwide cohort study. Aliment Pharmacol Ther. 2013;38(4):432–9.CrossRefPubMed
41.
go back to reference Chan AT, Arber N, Burn J, Chia WK, Elwood P, Hull MA, et al. Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev Res (Phila). 2012;5(2):164–78.CrossRef Chan AT, Arber N, Burn J, Chia WK, Elwood P, Hull MA, et al. Aspirin in the chemoprevention of colorectal neoplasia: an overview. Cancer Prev Res (Phila). 2012;5(2):164–78.CrossRef
42.
go back to reference Chia WK, Ali R, Toh HC. Aspirin as adjuvant therapy for colorectal cancer--reinterpreting paradigms. Nat Rev Clin Oncol. 2012;9(10):561–70.CrossRefPubMed Chia WK, Ali R, Toh HC. Aspirin as adjuvant therapy for colorectal cancer--reinterpreting paradigms. Nat Rev Clin Oncol. 2012;9(10):561–70.CrossRefPubMed
43.
go back to reference Wang D, DuBois RN. The role of anti-inflammatory drugs in colorectal cancer. Annu Rev Med. 2013;64:131–44.CrossRefPubMed Wang D, DuBois RN. The role of anti-inflammatory drugs in colorectal cancer. Annu Rev Med. 2013;64:131–44.CrossRefPubMed
Metadata
Title
Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma
Authors
Curtis J Henry
Rebecca L Sedjo
Andrii Rozhok
Jennifer Salstrom
Dennis Ahnen
Theodore R Levin
Ralph D’Agostino Jr
Steven Haffner
James DeGregori
Tim Byers
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1115-2

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine