Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 1/2010

01-01-2010

The −174 G/C Polymorphism in Interleukin-6 (IL-6) Promoter Region is Associated with Serum IL-6 and Carcinoembryonic Antigen Levels in Patients with Colorectal Cancers in Taiwan

Authors: Kun-Yun Yeh, Ying-Ying Li, Ling-Ling Hsieh, Jim-Ray Chen, Rei-Ping Tang

Published in: Journal of Clinical Immunology | Issue 1/2010

Login to get access

Abstract

Introduction

We investigated the associations between −174 G/C polymorphism of interleukin-6 (IL-6) gene promoter and serum IL-6 and carcinoembryonic antigen (CEA) levels in Taiwanese patients with colorectal cancer (CRC).

Results and Discussion

The frequency of the G allele was only 0.043, which is significantly lower compared to Western analogs. On grouping genotypes as G-positive (GG and CG) and G-negative (GG), the average IL-6 level and CEA levels were significantly lower in G-positive patients than in G-negative analogs (IL-6, 3.56 ± 4.38 vs. 15.38 ± 9.52 pg/ml, P = 0.021; CEA, 27.7 ± 25.7 vs. 157.7 ± 59.6 ng/ml, P = 0.012). The patients without the G allele had higher incidences of synchronous cancers of other origins (P = 0.003).

Conclusion

In conclusion, ethnicity affects the status of −174 G/C IL-6 polymorphism. This polymorphism status consequently influences the expressions of serum IL-6 and CEA and incidences of synchronous cancers of other origins.
Literature
1.
Chang KT, Huang CY, Tsai CM, Chiu CH, Lok YY. Role of IL-6 in neuroendocrine differentiation and chemosensitivity of non-small cell lung cancer. Am J Physiol Lung Cell Mol Physiol. 2005;289(3):L438.CrossRefPubMed
2.
Chang KT, Tsai CM, Chiou YC, Chiu CH, Jeng KS, Huang CY. IL-6 induces neuroendocrine dedifferentiation and cell proliferation in non-small cell lung cancer cells. Am J Physiol Lung Cell Mol Physiol. 2005;289(3):L446.CrossRefPubMed
3.
Yamaji H, Iizasa T, Koh E, Suzuki M, Otsuji M, Chang H, et al. Correlation between interleukin 6 production and tumor proliferation in non-small cell lung cancer. Cancer Immunol Immunother. 2004;53(9):786.CrossRefPubMed
4.
Shariat SF, Andrews B, Kattan MW, Kim J, Wheeler TM, Slawin KM. Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis. Urology. 2001;58(6):1008.CrossRefPubMed
5.
Abildgaard N, Glerup H, Rungby J, Bendix-Hansen K, Kassem M, Brixen K, et al. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma. Eur J Haematol. 2000;64(2):121.CrossRefPubMed
6.
Goydos JS, Brumfield AM, Frezza E, Booth A, Lotze MT, Carty SE. Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma: validation of utility as a clinical marker. Ann Surg. 1998;227(3):398.CrossRefPubMed
7.
Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332(6159):83.CrossRefPubMed
8.
Scambia G, Testa U, Benedetti Panici P, Foti E, Martucci R, Gadducci A, et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer. 1995;71(2):354.PubMed
9.
Lu C, Sheehan C, Rak JW, Chambers CA, Hozumi N, Kerbel RS. Endogenous interleukin 6 can function as an in vivo growth-stimulatory factor for advanced-stage human melanoma cells. Clin Cancer Res. 1996;2(8):1417.PubMed
10.
Yanagawa H, Sone S, Takahashi Y, Haku T, Yano S, Shinohara T, et al. Serum levels of interleukin 6 in patients with lung cancer. Br J Cancer. 1995;71(5):1095.PubMed
11.
Eustace D, Han X, Gooding R, Rowbottom A, Riches P, Heyderman E. Interleukin-6 (IL-6) functions as an autocrine growth factor in cervical carcinomas in vitro. Gynecol Oncol. 1993;50(1):15.CrossRefPubMed
12.
Miki S, Iwano M, Miki Y, Yamamoto M, Tang B, Yokokawa K, et al. Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett. 1989;250(2):607.CrossRefPubMed
13.
Oka M, Yamamoto K, Takahashi M, Hakozaki M, Abe T, Iizuka N, et al. Relationship between serum levels of interleukin 6, various disease parameters and malnutrition in patients with esophageal squamous cell carcinoma. Cancer Res. 1996;56(12):2776.PubMed
14.
Zhang GJ, Adachi I. Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res. 1999;19(2B):1427.PubMed
15.
Wu CW, Wang SR, Chao MF, Wu TC, Lui WY, P'eng FK, et al. Serum interleukin-6 levels reflect disease status of gastric cancer. Am J Gastroenterol. 1996;91(7):1417.PubMed
16.
Mouawad R, Benhammouda A, Rixe O, Antoine EC, Borel C, Weil M, et al. Endogenous interleukin 6 levels in patients with metastatic malignant melanoma: correlation with tumor burden. Clin Cancer Res. 1996;2(8):1405.PubMed
17.
Berek JS, Chung C, Kaldi K, Watson JM, Knox RM, Martinez-Maza O. Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol. 1991;164(4):1038.PubMed
18.
Ueda T, Shimada E, Urakawa T. Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. J Gastroenterol. 1994;29(4):423.CrossRefPubMed
19.
Belluco C, Nitti D, Frantz M, Toppan P, Basso D, Plebani M, et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol. 2000;7(2):133.CrossRefPubMed
20.
Nakagoe T, Tsuji T, Sawai T, Tanaka K, Hidaka S, Shibasaki S, et al. Increased serum levels of interleukin-6 in malnourished patients with colorectal cancer. Cancer Lett. 2003;202(1):109.CrossRefPubMed
21.
Nakagoe T, Tsuji T, Sawai T, Tanaka K, Hidaka S, Shibasaki S, et al. The relationship between circulating interleukin-6 and carcinoembryonic antigen in patients with colorectal cancer. Anticancer Res. 2003;23(4):3561.PubMed
22.
Esfandi F, Mohammadzadeh Ghobadloo S, Basati G. Interleukin-6 level in patients with colorectal cancer. Cancer Lett. 2006;244(1):76.CrossRefPubMed
23.
Schneider MR, Hoeflich A, Fischer JR, Wolf E, Sordat B, Lahm H. Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells. Cancer Lett. 2000;151(1):31.CrossRefPubMed
24.
Dansky-Ullmann C, Salgaller M, Adams S, Schlom J, Greiner JW. Synergistic effects of IL-6 and IFN-gamma on carcinoembryonic antigen (CEA) and HLA expression by human colorectal carcinoma cells: role for endogenous IFN-beta. Cytokine. 1995;7(2):118.CrossRefPubMed
25.
Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369.CrossRefPubMed
26.
Bonafe M, Olivieri F, Cavallone L, Giovagnetti S, Mayegiani F, Cardelli M, et al. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol. 2001;31(8):2357.CrossRefPubMed
27.
Olivieri F, Bonafe M, Cavallone L, Giovagnetti S, Marchegiani F, Cardelli M, et al. The −174 C/G locus affects in vitro/in vivo IL-6 production during aging. Exp Gerontol. 2002;37(2–3):309.CrossRefPubMed
28.
Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000;148(2):209.CrossRefPubMed
29.
Pola R, Flex A, Gaetani E, Lago AD, Gerardino L, Pola P, et al. The −174 G/C polymorphism of the interleukin-6 gene promoter is associated with Alzheimer's disease in an Italian population [corrected]. NeuroReport. 2002;13(13):1645.CrossRefPubMed
30.
Pola R, Flex A, Gaetani E, Pola P, Bernabei R. The −174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population. J Hum Hypertens. 2002;16(9):637.CrossRefPubMed
31.
Pola R, Gaetani E, Flex A, Aloi F, Papaleo P, Gerardino L, et al. −174 G/C interleukin-6 gene polymorphism and increased risk of multi-infarct dementia: a case–control study. Exp Gerontol. 2002;37(7):949.CrossRefPubMed
32.
Jahromi MM, Millward BA, Demaine AG. A polymorphism in the promoter region of the gene for interleukin-6 is associated with susceptibility to type 1 diabetes mellitus. J Interferon Cytokine Res. 2000;20(10):885.CrossRefPubMed
33.
Flex A, Gaetani E, Pola R, Santoliquido A, Aloi F, Papaleo P, et al. The −174 G/C polymorphism of the interleukin-6 gene promoter is associated with peripheral artery occlusive disease. Eur J Vasc Endovasc Surg. 2002;24(3):264.CrossRefPubMed
34.
Ferrari SL, Garnero P, Emond S, Montgomery H, Humphries SE, Greenspan SL. A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women. Arthritis Rheum. 2001;44(1):196.CrossRefPubMed
35.
Basso F, Lowe GD, Rumley A, McMahon AD, Humphries SE. Interleukin-6 −174 G>C polymorphism and risk of coronary heart disease in West of Scotland coronary prevention study (WOSCOPS). Arterioscler Thromb Vasc Biol. 2002;22(4):599.CrossRefPubMed
36.
Theodoropoulos G, Papaconstantinou I, Felekouras E, Nikiteas N, Karakitsos P, Panoussopoulos D, et al. Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer. World J Gastroenterol. 2006;12(31):5037.PubMed
37.
Slattery ML, Wolff RK, Herrick JS, Caan BJ, Potter JD. IL6 genotypes and colon and rectal cancer. Cancer Causes Control. 2007;18(10):1095.CrossRefPubMed
38.
Landi S, Moreno V, Gioia-Patricola L, Guino E, Navarro M, de Oca J, et al. Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activated receptor gamma with colorectal cancer. Cancer Res. 2003;63(13):3560.PubMed
39.
Belluco C, Olivieri F, Bonafe M, Giovagnetti S, Mammano E, Scalerta R, et al. −174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res. 2003;9(6):2173.PubMed
40.
Lim CS, Zheng S, Kim YS, Ahn C, Han JS, Kim S, et al. The −174 G to C polymorphism of interleukin-6 gene is very rare in Koreans. Cytokine. 2002;19(1):52.CrossRefPubMed
41.
Zhai R, Liu G, Yang C, Huang C, Wu C, Christiani DC. The G to C polymorphism at −174 of the interleukin-6 gene is rare in a Southern Chinese population. Pharmacogenetics. 2001;11(8):699.CrossRefPubMed
42.
Nakajima T, Ota N, Yoshida H, Watanabe S, Suzuki T, Emi M. Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women. Genes Immun. 1999;1(2):115.CrossRefPubMed
43.
Hayakawa T, Takamura T, Hisada A, Abe T, Nomura G, Kobayashi K. IL-6 gene polymorphism −174 G/C does not contribute substantially to hyperlipidaemia and type II diabetes mellitus in Japanese men. Diabetologia. 2002;45(3):453.CrossRefPubMed
44.
Cox ED, Hoffmann SC, DiMercurio BS, Wesley RA, Harlan DM, Kirk AD, et al. Cytokine polymorphic analyses indicate ethnic differences in the allelic distribution of interleukin-2 and interleukin-6. Transplantation. 2001;72(4):720.CrossRefPubMed
45.
Olomolaiye O, Wood NA, Bidwell JL. A novel NlaIII polymorphism in the human IL-6 promoter. Eur J Immunogenet. 1998;25(2–3):267.PubMed
46.
Litovkin KV, Domenyuk VP, Bubnov VV, Zaporozhan VN. Interleukin-6 −174 G/C polymorphism in breast cancer and uterine leiomyoma patients: a population-based case control study. Exp Oncol. 2007;29(4):295.PubMed
47.
Duch CR, Figueiredo MS, Ribas C, Almeida MS, Colleoni GW, Bordin JO. Analysis of polymorphism at site −174 G/C of interleukin-6 promoter region in multiple myeloma. Braz J Med Biol Res. 2007;40(2):265.PubMed
48.
Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000;275(24):18138.CrossRefPubMed
49.
Pritts T, Hungness E, Wang Q, Robb B, Hershko D, Hasselgren PO. Mucosal and enterocyte IL-6 production during sepsis and endotoxemia—role of transcription factors and regulation by the stress response. Am J Surg. 2002;183(4):372.CrossRefPubMed
50.
51.
Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei XF, et al. IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest. 1998;101(2):311.CrossRefPubMed
52.
Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60(8):1185.CrossRefPubMed
53.
Robb BW, Hershko DD, Paxton JH, Luo GJ, Hasselgren PO. Interleukin-10 activates the transcription factor C/EBP and the interleukin-6 gene promoter in human intestinal epithelial cells. Surgery. 2002;132(2):226.CrossRefPubMed
54.
Iacopetta B, Grieu F, Joseph D. The −174 G/C gene polymorphism in interleukin-6 is associated with an aggressive breast cancer phenotype. Br J Cancer. 2004;90(2):419.CrossRefPubMed
55.
Vairaktaris E, Yiannopoulos A, Vylliotis A, Yapijakis C, Derka S, Vassiliou S, et al. Strong association of interleukin-6 −174 G>C promoter polymorphism with increased risk of oral cancer. Int J Biol Markers. 2006;21(4):246.PubMed
56.
de Souza NC Nogueira, Brenna SM, Campos F, Syrjanen KJ, Baracat EC, Silva ID. Interleukin-6 polymorphisms and the risk of cervical cancer. Int J Gynecol Cancer. 2006;16(3):1278.CrossRef
57.
Gangwar R, Mittal B, Mittal RD. Association of interleukin-6 −174 G>C promoter polymorphism with risk of cervical cancer. Int J Biol Markers. 2009;24(1):11.PubMed
58.
Heikkila K, Harris R, Lowe G, Rumley A, Yarnell J, Gallacher J, et al. Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control. 2009;20(1):15.CrossRefPubMed
59.
Nusrat A, Sitaraman SV, Neish A. Interaction of bacteria and bacterial toxins with intestinal epithelial cells. Curr Gastroenterol Rep. 2001;3(5):392.CrossRefPubMed
60.
Abdul M, Hoosein N. Relationship of the interleukin-1 system with neuroendocrine and exocrine markers in human colon cancer cell lines. Cytokine. 2002;18(2):86.CrossRefPubMed
61.
Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003;374(Pt 1):1.CrossRefPubMed
62.
Cahill CM, Rogers JT. Interleukin (IL) 1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IkappaB kinase alpha pathway targeting activator protein-1. J Biol Chem. 2008;283(38):25900.CrossRefPubMed
Metadata
Title
The −174 G/C Polymorphism in Interleukin-6 (IL-6) Promoter Region is Associated with Serum IL-6 and Carcinoembryonic Antigen Levels in Patients with Colorectal Cancers in Taiwan
Authors
Kun-Yun Yeh
Ying-Ying Li
Ling-Ling Hsieh
Jim-Ray Chen
Rei-Ping Tang
Publication date
01-01-2010
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 1/2010
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-009-9324-6

Other articles of this Issue 1/2010

Journal of Clinical Immunology 1/2010 Go to the issue

OriginalPaper

Elevated Production of B Cell Chemokine CXCL13 is Correlated with Systemic Lupus Erythematosus Disease Activity

OriginalPaper

Mycobacterial ESAT-6 and katG are Recognized by Sarcoidosis CD4+ T Cells When Presented by the American Sarcoidosis Susceptibility Allele, DRB1*1101

OriginalPaper

A New Model of Induced Experimental Systemic Lupus Erythematosus (SLE) in Pigs and Its Amelioration by Treatment with a Tolerogenic Peptide

OriginalPaper

Long-Term Cerebrospinal Fluid and Blood Lymphocyte Dynamics After Rituximab for Pediatric Opsoclonus-Myoclonus

OriginalPaper

Disparate Role of LIGHT in Organ-specific Donor T Cells Activation and Effector Molecules in MHC Class II Disparate GVHD

OriginalPaper

Association of Interferon-Gamma Gene Polymorphisms in Taiwanese Children with Biliary Atresia
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits