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Circulating cytokines and gastric cancer risk

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Abstract

Purpose

Chronic inflammation has been hypothesized to play a significant role in the aetiology of cancer, including gastric cancer. In the present study, we sought to examine pre-diagnostic systemic cytokine levels in plasma, which can be seen as markers of aggregate inflammation, and risk of distal gastric cancer in a case–control study nested within the prospective Shanghai Men’s Health Study.

Methods

Circulating levels of eight inflammation-related cytokines were measured in the plasma collected at baseline for 180 incident cases of distal gastric cancer and 358 matched controls. Helicobacter pylori sero-positivity was assessed using multiplex serology. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CI).

Results

Individuals with IL-8 levels above the lowest quartile were at twofold increased odds of gastric cancer [OR 1.91 (95 % CI 1.05–3.46), OR 2.10 (95 % CI 1.19–3.74), and OR 2.30 (95 % CI 1.26–4.19), for the second through fourth quartiles, respectively]. While there were suggestions of an increase in risk with increased level of many of the other cytokines measured (IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ), no significant associations were found at the p < 0.05 level. Infection with CagA-positive H. pylori did not modify these associations.

Conclusions

In a population with high gastric cancer incidence and high H. pylori prevalence, increased circulating levels of IL-8 may indicate increased risk of gastric cancer. These findings add to our understanding of the disease and further efforts to uncover biomarkers of disease risk.

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References

  1. Keibel A, Singh V, Sharma MC (2009) Inflammation, microenvironment, and the immune system in cancer progression. Curr Pharm Des 15(17):1949–1955

    Article  PubMed  CAS  Google Scholar 

  2. Stoicov C, Li H, Cerny J, Houghton JM (2009) How the study of Helicobacter infection can contribute to the understanding of carcinoma development. Clin Microbiol Infect 15(9):813–822

    Article  PubMed  CAS  Google Scholar 

  3. Abnet CC, Freedman ND, Kamangar F, Leitzmann MF, Hollenbeck AR, Schatzkin A (2009) Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis. Br J Cancer 100(3):551–557

    Article  PubMed  CAS  Google Scholar 

  4. Wang WH, Huang JQ, Zheng GF, Lam SK, Karlberg J, Wong BC-Y (2003) Non-steroidal anti-inflammatory drug use and risk of gastric cancer: a systematic review and meta-analysis. J Natl Cancer Inst 95(23):1784–1791

    Article  PubMed  CAS  Google Scholar 

  5. Epplein M, Nomura AM, Wilkens LR, Henderson BE, Kolonel LN (2009) Nonsteroidal antiinflammatory drugs and risk of gastric adenocarcinoma: the multiethnic cohort study. Am J Epidemiol 170(4):507–514

    Article  PubMed  Google Scholar 

  6. Schneider BG, Camargo MC, Ryckman KK, Sicinschi LA, Piazuelo MB, Zabaleta J, Correa P, Williams SM (2008) Cytokine polymorphisms and gastric cancer risk: an evolving view. Cancer Biol Ther 7(2):157–162

    Article  PubMed  CAS  Google Scholar 

  7. Yu J, Zeng Z, Wang S, Tian L, Wu J, Xue L, Lee CW, Zhang M, Goggins WB, Chen M, Hu P, Sung JJ (2010) IL-1B-511 polymorphism is associated with increased risk of certain subtypes of gastric cancer in Chinese: a case-control study. Am J Gastroenterol 105(3):557–564

    Article  PubMed  CAS  Google Scholar 

  8. Cai H, Zheng W, Xiang YB, Xu WH, Yang G, Li H, Shu XO (2007) Dietary patterns and their correlates among middle-aged and elderly Chinese men: a report from the Shanghai Men’s Health Study. Br J Nutr 98(5):1006–1013

    Article  PubMed  CAS  Google Scholar 

  9. Lee SA, Wen W, Xu WH, Zheng W, Li H, Yang G, Xiang YB, Shu XO (2008) Prevalence of obesity and correlations with lifestyle and dietary factors in Chinese men. Obesity (Silver Spring) 16(6):1440–1447

    Article  Google Scholar 

  10. Zheng W, Chow WH, Yang G, Jin F, Rothman N, Blair A, Li HL, Wen W, Ji BT, Li Q, Shu XO, Gao YT (2005) The Shanghai women’s health study: rationale, study design, and baseline characteristics. Am J Epidemiol 162(11):1123–1131

    Article  PubMed  Google Scholar 

  11. Michel A, Waterboer T, Kist M, Pawlita M (2009) Helicobacter pylori multiplex serology. Helicobacter 14(6):525–535

    Article  PubMed  CAS  Google Scholar 

  12. Epplein M, Zheng W, Xiang YB, Peek RM Jr, Li H, Correa P, Gao J, Michel A, Cai Q, Pawlita M, Shu XO (2012) Prospective study of Helicobacter pylori biomarkers for gastric cancer risk among Chinese men. Cancer Epi Biomarkers Prev 21(12):2185–2192

    Article  CAS  Google Scholar 

  13. Waterboer T, Sehr P, Michael KM, Franceschi S, Nieland JD, Joos TO, Templin MF, Pawlita M (2005) Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem 51(10):1845–1853

    Article  PubMed  CAS  Google Scholar 

  14. Waterboer T, Sehr P, Pawlita M (2006) Suppression of non-specific binding in serological Luminex assays. J Immunol Methods 309(1–2):200–204

    Article  PubMed  CAS  Google Scholar 

  15. Epplein M, Signorello LB, Zheng W, Peek RM Jr, Michel A, Williams SM, Pawlita M, Correa P, Cai Q, Blot WJ (2011) Race, African ancestry, and Helicobacter pylori infection in a low-income United States population. Cancer Epidemiol Biomarkers Prev 20(5):826–834

    Article  PubMed  Google Scholar 

  16. Wong HL, Rabkin CS, Shu XO, Pfeiffer RM, Cai Q, Ji BT, Yang G, Li HL, Rothman N, Gao YT, Zheng W, Chow WH (2011) Systemic cytokine levels and subsequent risk of gastric cancer in Chinese Women. Cancer Sci 102(10):1911–1915

    Article  PubMed  CAS  Google Scholar 

  17. Macri A, Versaci A, Loddo S, Scuderi G, Travagliante M, Trimarchi G, Teti D, Famulari C (2006) Serum levels of interleukin 1beta, interleukin 8 and tumour necrosis factor alpha as markers of gastric cancer. Biomarkers 11(2):184–193

    Article  PubMed  CAS  Google Scholar 

  18. Konturek SJ, Starzynska T, Konturek PC, Karczewska E, Marlicz K, Lawniczak M, Jaroszewicz-Heigelman H, Bielanski W, Hartwich A, Ziemniak A, Hahn EG (2002) Helicobacter pylori and CagA status, serum gastrin, interleukin-8 and gastric acid secretion in gastric cancer. Scand J Gastroenterol 37(8):891–898

    Article  PubMed  CAS  Google Scholar 

  19. Xue H, Liu J, Lin B, Wang Z, Sun J, Huang G (2012) A meta-analysis of interleukin-8-251 promoter polymorphism associated with gastric cancer risk. PLoS ONE 7(1):e28083

    Article  PubMed  CAS  Google Scholar 

  20. Lee SA, Kallianpur A, Xiang YB, Wen W, Cai Q, Liu D, Fazio S, Linton MF, Zheng W, Shu XO (2007) Intra-individual variation of plasma adipokine levels and utility of single measurement of these biomarkers in population-based studies. Cancer Epidemiol Biomarkers Prev 16(11):2464–2470

    Article  PubMed  CAS  Google Scholar 

  21. Evans C, Morrison I, Heriot AG, Bartlett JB, Finlayson C, Dalgleish AG, Kumar D (2006) The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival. Br J Cancer 94(10):1412–1419

    Article  PubMed  CAS  Google Scholar 

  22. Manavalan JS, Hernandez L, Shah JG, Konikkara J, Naiyer AJ, Roland AL, Ciaccio E, Minaya MT, Green PH, Bhagat G (2009) Serum cytokine elevations in celiac disease: association with disease presentation. Hum Immunol 71(1):50–57

    Article  Google Scholar 

  23. Pine SR, Mechanic LE, Enewold L, Chaturvedi AK, Katki HA, Zheng YL, Bowman ED, Engels EA, Caporaso NE, Harris CC (2011) Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer. J Natl Cancer Inst 103(14):1112–1122

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Cancer Institute at the National Institutes of Health (K07 CA151782-01A1 to M.E. and R01 CA82729-11 to X.-O.S.) and the Joint Initiative for Innovation and Research of the German Helmholtz Association (A.M. and M.P.). The plasma sample preparations were performed at the Survey and Biospecimen Core, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). R.M.P. is supported by DK R01 58587, CA R01 77955, CA P01 116087, and DK P30 058404.

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Authors and Affiliations

  1. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 6th Floor, Nashville, TN, 37203-1738, USA

    Meira Epplein, Qiuyin Cai, Jie Wu, Wei Zheng & Xiao-Ou Shu

  2. Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaoting University School of Medicine, Shanghai, China

    Yong-Bing Xiang, Honglan Li & Jing Gao

  3. Division of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University, Nashville, TN, USA

    Richard M. Peek Jr. & Pelayo Correa

  4. Infection and Cancer Program, Division of Genome Modifications and Carcinogenesis, German Cancer Research Center (DFKZ), Heidelberg, Germany

    Angelika Michel & Michael Pawlita

Authors
  1. Meira Epplein
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  2. Yong-Bing Xiang
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  3. Qiuyin Cai
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  4. Richard M. Peek Jr.
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  5. Honglan Li
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  6. Pelayo Correa
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  7. Jing Gao
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  8. Jie Wu
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  9. Angelika Michel
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  10. Michael Pawlita
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  11. Wei Zheng
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  12. Xiao-Ou Shu
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Corresponding author

Correspondence to Meira Epplein.

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Epplein, M., Xiang, YB., Cai, Q. et al. Circulating cytokines and gastric cancer risk. Cancer Causes Control 24, 2245–2250 (2013). https://doi.org/10.1007/s10552-013-0284-z

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  • DOI: https://doi.org/10.1007/s10552-013-0284-z

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