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Genetic polymorphisms of interleukin-1 beta (IL-1B) and IL-1 receptor antagonist (IL-1RN) and breast cancer risk in Korean women

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Abstract

Objective

To evaluate the potential role of genetic polymorphisms of interleukin-1 beta (IL-1B) and IL-1 receptor antagonist (IL-1RN) on breast cancer development, a hospital-based case-control study was conducted in Korea.

Methods

Histologically confirmed breast cancer cases (n = 560) and controls (n = 509) without cancer history were recruited from three teaching hospitals in Seoul between September 1998 and January 2002. Information on risk factors of breast cancer were collected by interviewed questionnaire. Genotypes of IL-1B (-31C/T) and IL-1RN (86 bp variable number tandom repeats in intron 2) were determined by PCR-CTPP (confronting two-pair primers) and PCR, respectively. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression model.

Results

The IL-1RN *2-allele was associated with decreased breast cancer risk with marginal significance (OR = 0.7, 95% CI  = 0.48–1.05). The IL-1B CC or TC genotype was not associated with decreased risk of breast cancer (OR = 0.9, 95% CI  = 0.65–1.16). However, combination of IL-1B C-allele (CT or CC) and IL-1RN *2-allele containing genotypes significantly decreased the risk of breast cancer (OR = 0.6, 95% CI = 0.39–0.99). A moderately decreasing trend of risk was observed as the number of ‘putative low risk’ allele increased (p for trend = 0.07). Suggestive combined effect on breast cancer risk was also observed between body mass index (BMI) and IL-1RN non-*2 allele: women with higher BMI and IL-1RN non-*2 allele had 1.7-fold higher risk than women with lower BMI and IL-1RN*2 genotypes.

Conclusion

Our results suggest that genetic polymorphisms of interleukin-1 may play a role in the individual susceptibility for breast cancer development in Korean women.

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References

  1. Jin L, Yuan RQ, Fuchs A, Yao Y, Joseph A, Schwall R, Schnitt SJ, Guida A, Hastings HM, Andres J, Turkel G, Polverini PJ, Goldberg ID, Rosen EM, 1997 Expression of interleukin-1beta in human breast carcinoma Cancer 80(3): 421–434

    Article  PubMed  CAS  Google Scholar 

  2. Kurtzman SH, Anderson KH, Wang Y, Miller LJ, Renna M, Stankus M, Lindquist RR, Barrows G, Kreutzer DL, 1999 Cytokines in human breast cancer: IL-1 alpha and IL-1 beta expression Oncol Rep 6(1): 65–70

    PubMed  CAS  Google Scholar 

  3. Miller LJ, Kurtzman SH, Anderson K, Wang Y, Stankus M, Renna M, Lindquist R, Barrows G, Kreutzer DL, 2000 Interleukin-1 family expression in human breast cancer: interleukin-1 receptor antagonist Cancer Invest 18(4): 293–302

    Article  PubMed  CAS  Google Scholar 

  4. Witkin SS, Gerber S, Ledger WJ, 2002: Influence of interleukin-1 receptor antagonist gene polymorphism on disease Clin Infect Dis 34: 204–209

    Article  PubMed  CAS  Google Scholar 

  5. Coussens LM, Werb Z, 2002 Inflammation and cancer Nature 420: 860–867

    Article  PubMed  CAS  Google Scholar 

  6. El-Omar EM, Carrington M, Cho WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF, Rabkin CS, 2000 Interleukin-1 polymorphisms associated with increased risk of gastric cancer Nature 404(6776): 398–402

    Article  PubMed  CAS  Google Scholar 

  7. Machado JC, Pharoah P, Sousa S, Carvalho R, Oliveira C, Figueiredo C, Amorim A, Seruca R, Caldas C, Carneiro F, Sobrinho-Simoes M, 2001 Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma Gastroenterology 121(4): 823–829

    Article  PubMed  CAS  Google Scholar 

  8. Sehouli J, Mustea A, Konsgen D, Katsares I, Lichtenegger W, 2002 Polymorphism of IL-1 receptor antagonist gene: role in cancer Anticancer Res. 22(6A): 3421–3424

    PubMed  CAS  Google Scholar 

  9. Ito LS, Iwata H, Hamajima N, Saito T, Matsuo K, Mizutani M, Iwase T, Miura S, Okuma K, Inoue M, Hirose K, Tajima K, 2002 Significant reduction in breast cancer risk for Japanese women with interleukin 1B -31 CT/TT relative to CC genotype Jpn J Clin Oncol 32(10): 398–402

    Article  PubMed  Google Scholar 

  10. Smith KC, Bateman AC, Fussell HM, Howell WM, 2004 Cytokine gene polymorphisms and breast cancer susceptibility and prognosis Eur J Immunogenet 31(4): 167–173

    Article  PubMed  CAS  Google Scholar 

  11. Wilkinson RJ, Patel P, Llewelyn M, Hirsch CS, Pasvol G, Snounou G, Davidson RN, Toossi Z, 1999 Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis J Exp Med 189 (12): 1863–1874

    Article  PubMed  CAS  Google Scholar 

  12. Dabrowski MP, Stankiewicz W, Plusa T, Chcialowski A, Szmigielski S, 2001 Competition of IL-1 and IL-1ra determines lymphocyte response to delayed stimulation with PHA Mediators Inflamm 10(3): 101–107

    Article  PubMed  CAS  Google Scholar 

  13. Danis VA, Millington M, Hyland VJ, Grennan D, 1995: Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism Clin Exp Immunol 99(2): 303–310

    Article  PubMed  CAS  Google Scholar 

  14. Bioque G, Crusius JB, Koutroubakisn I, Bouma G, Kostense PJ, Meuwissen SG, Pena AS, 1995 Allelic polymorphism in IL-1 beta and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease Clin Exp Immunol 102(2): 379–383

    Article  PubMed  CAS  Google Scholar 

  15. 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(3): 195–198

    Article  PubMed  CAS  Google Scholar 

  16. Hamajima N, Matsuo K, Saito T, Tajima K, Okuma K, Yamao K, Tominaga S, 2001 Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection Jap J Cancer Res 92: 383–389

    CAS  Google Scholar 

  17. Park SK, Yoo KY, Lee SJ, Kim SU, Ahn SH, Noh DY, Choe KJ, Strickland PT, Hirvonen A, Kang D, 2000 Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk Pharmacogenetics 10(4): 301–309

    Article  PubMed  CAS  Google Scholar 

  18. Lee KM, Park SK, Hamajima N, Tajima K, Yoo KY, Shin A, Noh DY, Ahn SH, Hirvonen A, Kang D, 2005: Genetic polymorphisms of TGF-β1 & TNF-β and breast cancer risk Br Cancer Res Treat 90(2):149–55

    Article  CAS  Google Scholar 

  19. Speirs V, Kerin MJ, Newton CJ, Walton DS, Green AR, Desain SB, Atkin SL, 1999 Evidence for transcriptional activation of ER alpha by IL-1beta in breast cancer cells Int J Oncol 15(6): 1251–1254

    PubMed  CAS  Google Scholar 

  20. Honma S, Shimodaira K, Shimizu Y, Tsuchiya N, Saito H, Yanaihara T, Okai T, 2002 The influence of inflammatory cytokines on estrogen production and cell proliferation in human breast cancer cells Endocr J 49(3): 371–377

    Article  PubMed  CAS  Google Scholar 

  21. Reichlin S, Chen G, Nicolson M, 2000 Blood to brain transfer of leptin in normal and interleukin-1beta-treated male rats Endocrinology 141(6): 1951–1954

    Article  PubMed  CAS  Google Scholar 

  22. Hu X, Juneja SC, Maihle NJ, Cleary MP, 2002 Leptin-a growth factor in normal and malignant breast cells and for normal mammary gland development J Natl Cancer Inst 94(22): 1704–1711

    PubMed  CAS  Google Scholar 

  23. Yin N, Wang D, Zhang H, Yi X, Sun X, Shi B, Wu H, Wu G, Wang X, 2004 Molecular mechanisms in the growth stimulation of breast cancer cells by leptin Cancer Res 64: 5870–5875

    Article  PubMed  CAS  Google Scholar 

  24. Rose DP, Komninou D, Stephenson GD, 2004 Obesity, adipocytokines, and insulin resistance in breast cancer Obes Rev 5(3): 153–165

    Article  PubMed  CAS  Google Scholar 

  25. Andus T, Daig R, Vogl D, Aschenbrenner E, Lock G, Hollerbach S, Kollinger M, Scholmerich J, Gross V, 1997 Imbalance of the interleukin 1 system in colonic mucosa-association with intestinal inflammation and interleukin 1 receptor antagonist genotype 2 Gut 41(5): 651–657

    Article  PubMed  CAS  Google Scholar 

  26. Tountas NA, Casini-Raggi V, Yang H, Di Giovine FS, Vecchi M, Kam L, Melani L, Pizarro TT, Rotter JI, Cominelli F, 1999 Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis Gastroenterology 117(4): 806–813

    Article  PubMed  CAS  Google Scholar 

  27. DeMichele A, Martin AM, Mick R, Gor P, Wary L, Klein-Cabral M, Athanasiadis G, Colligan T, Stadtmauer E, Weber B, 2003 Interleukin-6-174G→C polymorphism is associated with improved outcome in high-risk breast cancer Cancer Res 63: 8051–8056

    PubMed  CAS  Google Scholar 

  28. Lacopetta B, Grieu F, Joseph D, 2004 The -174G/C gene polymorphism in interleukin-6 is associated with an aggressive breast cancer phenotype Br J Cancer 90: 419–422

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This research was supported partly by grant (2003–022) from the Asan Institute for Life Sciences, Seoul, Korea.

Author information

Authors and Affiliations

  1. Cancer Research Institute, Institute of Environmental Medicine, SNUMRC, and Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, Korea

    Kyoung-Mu Lee, Ji-Yeob Choi, Keun-Young Yoo & Daehee Kang

  2. Graduate School of Public Health, Seoul National University, Seoul, Korea

    Kyoung-Mu Lee

  3. Department of Preventive Medicine, Konkuk University College of Medicine, Chungju, Korea

    Sue Kyung Park

  4. Departments of Preventive Medicine, Biostatistics and Medical Decision Making, Nagoya Graduated School of Medicine, Nagoya, Japan

    Nobuyuki Hamajima

  5. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

    Kazuo Tajima

  6. Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

    Dong-Young Noh

  7. Department of Surgery, Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea

    Sei-Hyun Ahn

  8. Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland

    Ari Hirvonen

  9. Cancer Research Institute and Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, Korea

    Daehee Kang

Authors
  1. Kyoung-Mu Lee
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  2. Sue Kyung Park
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  3. Nobuyuki Hamajima
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  4. Kazuo Tajima
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  10. Daehee Kang
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Corresponding author

Correspondence to Daehee Kang.

Appendix

Appendix

Oligonucleotide sequences of PCR primers, PCR products, and annealing temperatures for each polymorphic sites

Polymorphism

PCR primers

PCR products (bp)

Annealing temperature (C)

IL-1B T 31 C

(F1) 5′-AAT GTC GAC ATC AAC TGC A-3′

266

574a

54

(R1) 5′-CTC CCT CGC TGT TTT TAT A-3′

(F2) 5′-ACT TCT GCT TTT GAA AGC C-3′

345

(R2) 5′-TCA GCT GTT AGA TAA GCA G-3′

IL-1RN 86bp VNTR

(F) 5′-CTC AGC AAC ACT CCT AT-3′

240 for 2 repeats

54

(R) 5′-TCC TGG TCT GCA GGT AA-3′

  1. a Common product amplified by non-allele specific primers; (F1) and (R2).

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Lee, KM., Park, S.K., Hamajima, N. et al. Genetic polymorphisms of interleukin-1 beta (IL-1B) and IL-1 receptor antagonist (IL-1RN) and breast cancer risk in Korean women. Breast Cancer Res Treat 96, 197–202 (2006). https://doi.org/10.1007/s10549-005-9079-6

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  • DOI: https://doi.org/10.1007/s10549-005-9079-6

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