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01-09-2009 | Gastrointestinal Oncology

CRP Genetic Polymorphism Is Associated with Lymph Node Metastasis in Thoracic Esophageal Squamous Cell Cancer

Authors: Satoru Motoyama, MD, PhD, Masatomo Miura, PhD, Yudai Hinai, PhD, Kiyotomi Maruyama, MD, PhD, Shuetsu Usami, MD, Hajime Saito, MD, PhD, Yoshihiro Minamiya, MD, PhD, Shigeru Satoh, MD, PhD, Katsuyuki Murata, MD, PhD, Toshio Suzuki, PhD, Jun-ichi Ogawa, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2009

Abstract

Background

Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis.

Methods

The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-α and -β, interferon (IFN)-γ, transforming growth factor (TGF)- β, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12β were investigated using the polymerase chain reaction–restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis.

Results

For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively.

Conclusions

These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.

Orringer MB, Marshall B, Chang AC, Lee J, Pickens A, Lau CL. Two thousand transhiatal esophagectomies: changing trends, lessons learned. Ann Surg. 2007;246:363–72.PubMedCrossRef

Siewert JR, Stein HJ, Feith M, Bruecher BL, Bartels H, Fink U. Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world. Ann Surg. 2001;234:360–7.PubMedCrossRef

Mariette C, Piessen G, Briez N, Triboulet JP. The number of metastatic lymph nodes and the ratio between metastatic and examined lymph nodes are independent prognostic factors in esophageal cancer regardless of neoadjuvant chemoradiation or lymphadenectomy extent. Ann Surg. 2008;247:365–71.PubMedCrossRef

Wijnhoven BP, Tran KT, Esterman A, Bruecher BL, Bartels H, Fink U. An evaluation of prognostic factors and tumor staging of resected carcinoma of the esophagus. Ann Surg. 2007;245:717–25.PubMedCrossRef

Chiu PW, Chan KF, Lee YT, Sung JJ, Lau JY, Ng EK. Endoscopic submucosal dissection used for treating early neoplasia of the foregut using a combination of knives. Surg Endosc. 2008;22:777–83.PubMedCrossRef

Marnell L, Mold C, Du Clos TW. C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol. 2005;117:104–11.PubMedCrossRef

Fleming JS, Beaugié CR, Haviv I, Chenevix-Trench G, Tan OL. Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses. Mol Cell Endocrinol. 2006;247:4–21.PubMedCrossRef

Jackson JR, Seed MP, Kircher CH, Willoughby DA, Winkler JD. The codependence of angiogenesis and chronic inflammation. FASEB J. 1997;11:457–65.PubMed

Helzlsouer KJ, Erlinger TP, Platz EA. C-reactive protein levels and subsequent cancer outcomes: results from a prospective cohort study. Eur J Cancer. 2006;42:704–7.PubMedCrossRef

10.

Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.PubMedCrossRef

11.

Elliott RL, Blobe GC. Role of transforming growth factor Beta in human cancer. J Clin Oncol. 2005;23:2078–93.CrossRef

12.

Mangi MH, Newland AC. Interleukin-3 in hematology and oncology: current state of knowledge and future directions. Cytokines Cell Mol Ther. 1999;5:87–95.PubMed

13.

Erlinger TP, Platz EA, Rifai N, Helzlsouer KJ. C-reactive protein and the risk of incident colorectal cancer. JAMA. 2004;291:585–90.PubMedCrossRef

14.

Shimada H, Nabeya Y, Okazumi S, Matsubara H, Shiratori T, Aoki T, et al. Elevation of preoperative serum C-reactive protein level is related to poor prognosis in esophageal squamous cell carcinoma. J Surg Oncol. 2003;83:248–52.PubMedCrossRef

15.

Hashimoto K, Ikeda Y, Korenaga D, et al. The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular carcinoma. Cancer. 2005;103:1856–64.PubMedCrossRef

16.

Miyata Y, Koga S, Nishikido M, et al. Predictive values of acute phase reactants, basic fetoprotein, and immunosuppressive acidic protein for staging and survival in renal cell carcinoma. Urology. 2001;58:161–4.PubMedCrossRef

17.

Hefler LA, Concin N, Hofstetter G, et al. Serum C-reactive protein as independent prognostic variable in patients with ovarian cancer. Clin Cancer Res. 2008;14:710–4.PubMedCrossRef

18.

Carlson CS, Aldred SF, Lee PK, et al. Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. Am J Hum Genet. 2005;77:64–7.PubMedCrossRef

19.

Szalai AJ, Wu J, Lange EM, McCrory MA, Langefeld CD, Williams A. Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level. J Mol Med. 2005;83:440–7.PubMedCrossRef

20.

Motoyama S, Ishiyama K, Maruyama K, et al. Preoperative mapping of lymphatic drainage from the tumor using ferumoxide-enhanced magnetic resonance imaging in clinical submucosal thoracic squamous cell esophageal cancer. Surgery. 2007;141:736–47.PubMedCrossRef

21.

Wolford JK, Gruber JD, Ossowski VM, et al. A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab. 2003;78:136–44.PubMedCrossRef

22.

Russell AI, Cunninghame Graham DS, et al. Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum Mol Genet. 2004;13:137–47.PubMedCrossRef

23.

Eklund C, Kivimäki M, Islam MS, et al. C-reactive protein genetics is associated with carotid artery compliance in men in The Cardiovascular Risk in Young Finns Study. Atherosclerosis. 2008;196:841–8.PubMedCrossRef

24.

Day CP, Grove J, Daly AK, Stewart MW, Avery PJ, Walker M. Tumour necrosis factor-alpha gene promoter polymorphism and decreased insulin resistance. Diabetologia. 1998;41:430–4.PubMedCrossRef

25.

Skoog T, van’t Hooft FM, Kallin B, et al. A common functional polymorphism (C–>A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet. 1999;8:1443–9.PubMedCrossRef

26.

Kim TG, Kim HY, Lee SH, et al. Systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 homozygote in the Korean population. Hum Immunol. 1996;46:10–7.PubMedCrossRef

27.

Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV. A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol. 2000;61:863–6.PubMedCrossRef

28.

Shu XO, Gao YT, Cai Q, et al. Genetic polymorphisms in the TGF-beta 1 gene and breast cancer survival: a report from the Shanghai Breast Cancer Study. Cancer Res. 2004;64:836–9.PubMedCrossRef

29.

Graziano F, Ruzzo A, Santini D, et al. Prognostic role of interleukin-1beta gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer. J Clin Oncol. 2005;23:2339–45.PubMedCrossRef

30.

Lehtimäki T, Laaksonen R, Janatuinen T, et al. Interleukin-1B genotype modulates the improvement of coronary artery reactivity by lipid-lowering therapy with pravastatin: a placebo-controlled positron emission tomography study in young healthy men. Pharmacogenetics. 2003;13:633–9.PubMedCrossRef

31.

32.

Ross OA, Curran MD, Meenagh A, et al. Study of age-association with cytokine gene polymorphisms in an aged Irish population. Mech Ageing Dev. 2003;124:199–206.PubMedCrossRef

33.

Noguchi E, Shibasaki M, Arinami T, et al. Association of asthma and the interleukin-4 promoter gene in Japanese. Clin Exp Allergy. 1998;28:449–53.PubMedCrossRef

34.

Buraczynska M, Jozwiak L, Ksiazek P, Borowicz E, Mierzicki P. Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. Transl Res. 2007;150:101–5.PubMedCrossRef

35.

Wolford JK, Colligan PB, Gruber JD, Bogardus C. Variants in the interleukin 6 receptor gene are associated with obesity in Pima Indians. Mol Genet Metab. 2003;80:338–43.PubMedCrossRef

36.

Edwards-Smith CJ, Jonsson JR, Purdie DM, Bansal A, Shorthouse C, Powell EE. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa. Hepatology. 1999;30:526–30.PubMedCrossRef

37.

Hall MA, McGlinn E, Coakley G, et al. Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. Genes Immun. 2000;1:219–24.PubMedCrossRef

38.

Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.PubMedCrossRef

39.

Vakkila J, Lotze MT. Inflammation and necrosis promote tumour growth. Nat Rev Immunol. 2004;4:641–8.PubMedCrossRef

40.

Zeh HJ 3rd, Lotze MT. Addicted to death: invasive cancer and the immune response to unscheduled cell death. J Immunother. 2005;28:1–9.PubMedCrossRef

41.

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.PubMedCrossRef

42.

Marnell L, Mold C, Du Clos TW. C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol. 2005;117:104–11.PubMedCrossRef

43.

Lange LA, Carlson CS, Hindorff LA, et al. Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. JAMA. 2006;296:2703–11.PubMedCrossRef

44.

Miller DT, Zee RY, Suk Danik J, et al. Association of common CRP gene variants with CRP levels and cardiovascular events. Ann Hum Genet. 2005;69:623–38.PubMedCrossRef

45.

Siemes C, Visser LE, Coebergh JW, et al. C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol. 2006;24:5216–22.PubMedCrossRef

46.

Wen W, Cai Q, Xiang YB, et al. The modifying effect of C-reactive protein gene polymorphisms on the association between central obesity and endometrial cancer risk. Cancer. 2008;112:2409–16.PubMedCrossRef

47.

Ockene IS, Matthews CE, Rifai N, Ridker PM, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem. 2001;47:444–50.PubMed

48.

Wang HW, Sui SF. Dissociation and subunit rearrangement of membrane-bound human C-reactive proteins. Biochem Biophys Res Commun. 2001;288:75–9.PubMedCrossRef

49.

Marsik C, Sunder-Plassmann R, Jilma B, et al. The C-reactive protein (+)1444C/T alteration modulates the inflammation and coagulation response in human endotoxemia. Clin Chem. 2006;52:1952–7.PubMedCrossRef

Title: CRP Genetic Polymorphism Is Associated with Lymph Node Metastasis in Thoracic Esophageal Squamous Cell Cancer
Authors: Satoru Motoyama, MD, PhD
Masatomo Miura, PhD
Yudai Hinai, PhD
Kiyotomi Maruyama, MD, PhD
Shuetsu Usami, MD
Hajime Saito, MD, PhD
Yoshihiro Minamiya, MD, PhD
Shigeru Satoh, MD, PhD
Katsuyuki Murata, MD, PhD
Toshio Suzuki, PhD
Jun-ichi Ogawa, MD, PhD
Publication date: 01-09-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 9/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-009-0525-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

CRP Genetic Polymorphism Is Associated with Lymph Node Metastasis in Thoracic Esophageal Squamous Cell Cancer

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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