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Circulating IL-1β levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women

  • Original Paper
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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Long-term human papillomavirus (HPV) infection is a prerequisite for cervical cancer. IL-1β and IL-1Ra expression levels play an important role in cervical carcinogenesis. Several functional genetic variants in IL1B and IL-RN have been reported to be associated with IL-1β expression and cancer susceptibility. In the current study, we hypothesized that plasma IL-1β levels, IL-1B and IL-RN polymorphisms were candidate biomarkers for cervical cancer.

Methods

We measured plasma IL-1β levels and genotyped IL-1B and IL-RN polymorphisms in a case–control study of 404 cervical cancer cases and 404 controls in Chinese women.

Results

The mean plasma IL-1β levels in cervical cancer cases (42.19 ± 31.55 pg/ml) was significantly higher than those in controls (34.86 ± 22.68 pg/ml, P = 0.0002), and plasma IL-1β levels above the 75% quartiles in controls (IL-1β ≥ 46.94 pg/ml) were associated with a 1.74-fold significantly increased risk of cervical cancer [95% confidence interval (CI), 1.28–2.36], compared with those of lowest quartile. Multivariate logistic regression analyses revealed that the variant genotypes, IL-1B T-31C TC/CC and C-511T CT/TT, were associated with a significantly increased risk of cervical cancer [adjusted odds ratio (OR), 1.60; 95% CI, 1.16–2.21 for −31TC/CC, and adjusted OR, 1.52; 95% CI, 1.10–2.09 for −511CT/TT, respectively), especially among subjects having higher levels of IL-1β. However, IL-RN VNTR polymorphism was not associated with cervical cancer risk in the current study. Furthermore, the significant differences of IL-1β concentration between cervical cancer cases and controls were observed only among subjects carrying T-31C or C-511T variant genotypes.

Conclusion

Functional IL-1B genotypes may modify plasma IL-1β concentrations to contribute to the etiology of cervical cancer in Chinese women; however, further perspective studies are warranted to test the causal effects of IL-1β concentration in cervical carcinogenesis.

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Abbreviations

CI:

Confidence interval

HPV:

Human papillomavirus

IL-1β:

Interleukin-1β

LD:

Linkage disequilibrium

OR:

Odds ratio

RFLP:

Restriction fragment length polymorphism

SNPs:

Single nucleotide polymorphisms

VNTR:

Number of tandem repeats

References

  • Arend WP (2002) The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 13:323–340

    Article  CAS  PubMed  Google Scholar 

  • Arend WP, Malyak M, Guthridge CJ, Gabay C (1998) Interleukin-1 receptor antagonist: role in biology. Annu Rev Immuno l16:27–55

    Article  Google Scholar 

  • Behbakht K, Friedman J, Heimler I, Aroutcheva A, Simoes J, Faro S (2002) Role of the vaginal microbiological ecosystem and cytokine profile in the promotion of cervical dysplasia: a case–control study. Infect Dis Obstet Gynecol 10:181–186

    Article  PubMed  Google Scholar 

  • Belokrinitskaia TE, Vitkovskii IuA, Ponomareva IuN (2003) Role of cytokines in the development of immunologic and homeostatic disorders in advanced dysplasia and carcinoma of the uterine cervix. Vopr Onkol 49:51–54

    CAS  PubMed  Google Scholar 

  • Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF et al (1999) Cytokine gene polymorphism in human disease: on-balance line databases. Genes Immun 1:3–19

    Article  CAS  PubMed  Google Scholar 

  • Chang YW, Jang JY, Kim NH, Lee JW, Lee HJ, Jung WW et al (2005) Interleukin-1B (IL-1B) polymorphisms and gastric mucosal levels of IL-1beta cytokine in Korean patients with gastric cancer. Int J Cancer 114:465–471

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Wilkins LM, Aziz N, Cannings C, Wyllie DH, Bingle C et al (2006) Single nucleotide polymorphisms in the human interleukin-1B gene affect transcription according to haplotype context. Hum Mol Genet 15:519–529

    Article  CAS  PubMed  Google Scholar 

  • Dinarello CA (1991) Interleukin-1 and interleukin-1 antagonism. Blood 77:1627–1652

    CAS  PubMed  Google Scholar 

  • Dinarello CA, Wolff SM (1993) The role of interleukin-1 in disease. N Engl J Med 328:106–113

    Article  CAS  PubMed  Google Scholar 

  • El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA et al (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398–402

    Article  CAS  PubMed  Google Scholar 

  • El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB et al (2003) Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 124:1193–1201

    Article  CAS  PubMed  Google Scholar 

  • Francis SE, Camp NJ, Dewberry RM, Gunn J, Syrris P, Carter ND et al (1999) Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 99:861–866

    CAS  PubMed  Google Scholar 

  • Fujiwaki R, Iida K, Nakayama K, Kanasaki H, Hata K, Katabuchi H et al (2003) Clinical significance of interleukin-1 receptor antagonist in patients with cervical carcinoma. Gynecol Oncol 89:77–83

    Article  CAS  PubMed  Google Scholar 

  • Grimm C, Berger I, Tomovski C, Zeillinger R, Concin N, Leodolter S et al (2004) A polymorphism of the interleukin-1 receptor antagonist plays a prominent role within the interleukin-1 gene cluster in vulvar carcinogenesis. Gynecol Oncol 92:936–940

    Article  CAS  PubMed  Google Scholar 

  • Hirankarn N, Kimkong I, Kummee P, Tangkijvanich P, Poovorawan Y (2006) Interleukin-1beta gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection. World J Gastroenterol 12:776–779

    CAS  PubMed  Google Scholar 

  • Hu Z, Shao M, Chen Y, Zhou J, Qian J, Xu L et al (2006) Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer. Cancer Lett 236:269–275

    Article  CAS  PubMed  Google Scholar 

  • Kang S, Kim JW, Park NH, Song YS, Park SY, Kang SB et al (2007) Interleukin-1 beta-511 polymorphism and risk of cervical cancer. J Korean Med Sci 22:110–113

    Article  CAS  PubMed  Google Scholar 

  • Lind H, Haugen A, Zienolddiny S (2007) Differential binding of proteins to the IL1B-31 T/C polymorphism in lung epithelial cells. Cytokine 38:43–48

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Zhai X, Jin G, Hu Z, Wang S, Wang X et al (2006) Functional variants in the promoter of interleukin-1beta are associated with an increased risk of breast cancer: a case–control analysis in a Chinese population. Int J Cancer 118:2554–2558

    Article  CAS  PubMed  Google Scholar 

  • Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S et al (2003) A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology 125:364–371

    Article  CAS  PubMed  Google Scholar 

  • Mustea A, Sehouli J, Konsgen D, Stengel D, Sofroni D, Lichtenegger W (2003) Interleukin 1 receptor antagonist (IL-1 RA) polymorphism in women with cervical cancer. Anticancer Res 23:1099–1102

    CAS  PubMed  Google Scholar 

  • Noqueira de Souza NC, Brenna SM, Campos F, Syrjänen KJ, Baracat EC, Silva ID (2006) Interleukin-6 polymorphisms and the risk of cervical cancer. Int J Gynecol Cancer 16:1278–1282

    Article  Google Scholar 

  • Parkin DM, Bray F (2006) Chapter 2: the burden of HPV related cancers. Vaccine 24:S11–S25

    Article  Google Scholar 

  • Santtila S, Savinainen K, Hurme M (1998) Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 47:195–198

    Article  CAS  PubMed  Google Scholar 

  • Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A et al (1993) Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 91:403–404

    Article  CAS  PubMed  Google Scholar 

  • Tjiong MY, van der Vange N, ter Schegget JS, Burger MP, ten Kate FW, Out TA (2001) Cytokines in cervicovaginal washing fluid from patients with cervical neoplasia. Cytokine 14:357–360

    Article  CAS  PubMed  Google Scholar 

  • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19

    Article  CAS  PubMed  Google Scholar 

  • Zeng ZR, Hu PJ, Hu S, Pang RP, Chen MH, Ng M et al (2003) Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China. Gut 52:1684–1689

    Article  CAS  PubMed  Google Scholar 

  • Zienolddiny S, Ryberg D, Maggini V, Skaug V, Canzian F, Haugen A (2004) Polymorphisms of the interleukin-1β gene are associated with increased risk of non-small cell lung cancer. Int J Cancer 109:353–356

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Program for Changjiang Scholars and Innovative Research Team in University (IRT0631); Key Development Program of Nanjing Medical University (07NMUZ011) and Natural Science Basic Research Program of Jiangsu Colleges (08KJB330002).

Conflict of interest statement

The authors disclose no potential conflict of interest.

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Authors and Affiliations

  1. Laboratory of Reproductive Medicine, Nanjing Medical University, 210029, Nanjing, China

    Nianfeng Qian, Xiaojun Chen, Suping Han, Guangfu Jin, Xiaoyi Zhou, Jing Dong, Xinru Wang, Hongbing Shen & Zhibin Hu

  2. Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, 140 Hanzhong Rd, 210029, Nanjing, China

    Nianfeng Qian, Guangfu Jin, Xiaoyi Zhou, Jing Dong, Hongbing Shen & Zhibin Hu

  3. Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China

    Suping Han

  4. Tumor Hospital of Nantong City, 226000, Nantong, China

    Xiaojun Chen & Fulin Qiang

Authors
  1. Nianfeng Qian
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  2. Xiaojun Chen
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  3. Suping Han
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  4. Fulin Qiang
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  5. Guangfu Jin
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  6. Xiaoyi Zhou
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  7. Jing Dong
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  8. Xinru Wang
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  9. Hongbing Shen
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  10. Zhibin Hu
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Corresponding authors

Correspondence to Hongbing Shen or Zhibin Hu.

Additional information

N. Qian, X. Chen contributed equally.

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Qian, N., Chen, X., Han, S. et al. Circulating IL-1β levels, polymorphisms of IL-1B, and risk of cervical cancer in Chinese women. J Cancer Res Clin Oncol 136, 709–716 (2010). https://doi.org/10.1007/s00432-009-0710-5

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  • DOI: https://doi.org/10.1007/s00432-009-0710-5

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