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Tumor Biology

, Volume 37, Issue 12, pp 15813–15823 | Cite as

Association of single-nucleotide polymorphisms of high-mobility group box 1 with susceptibility and clinicopathological characteristics of uterine cervical neoplasia in Taiwanese women

  • Hsin-Hung Wu
  • Yu-Fan Liu
  • Shun-Fa Yang
  • Wea-Lung Lin
  • Shiuan-Chih Chen
  • Chih-Ping Han
  • Hsiang-Ling Wang
  • Long-Yau Lin
  • Po-Hui Wang
Original Article

Abstract

To date, no study associated the genetic polymorphisms of high-mobility group box 1 protein (HMGB1) with the development of uterine cervical cancer. We therefore conducted this study to investigate the associations of HMGB1 single-nucleotide polymorphisms (SNPs) with cervical carcinogenesis and clinicopathological characteristics of cancer patients. Five hundred two women, including 112 with invasive cancer, 85 with precancerous lesions of the uterine cervix, and 305 normal controls, were consecutively enrolled into this study. Analysis of HMGB1 SNPs was done by real-time polymerase chain reaction and genotyping. Our results found that the risk of susceptibility to cervical invasive cancer was 1.85 (95 % CI 1.12–3.04; p = 0.016) in women with TC and 1.99 (95 % CI 1.24–3.23; p = 0.005) in women with TC/CC after adjusting for age, using TT as a comparison reference in HMGB1 SNP rs1412125. In rs2249825, the increased risk was also seen for the development of cervical invasive cancer in women with CG [adjusted odds ratio (AOR) 2.04, 95 % CI 1.22–3.40; p = 0.006] or CG/GG (AOR 2.02, 95 % CI 1.22–3.32; p = 0.006) using CC as a comparison reference. An additional integrated in silico analysis confirmed that rs2249825 creates a binding site for v-Myb, which may affect HMGB1 expression. In conclusion, Taiwanese women with TC or TC/CC in HMGB1 SNP rs1412125 as well as CG or CG/GG in rs2249825 were susceptible to the development of cervical invasive cancer.

Keywords

Single-nucleotide polymorphism HMGB1 Cervical cancer 

Notes

Compliance with ethical standards

The Chung Shan Medical University Hospital Institutional Review Board approved this study, and informed written consents were obtained from all subjects (CSMUH IRB: CS12219, CS14014)

Conflicts of interest

None.

References

  1. 1.
    Javaherian K, Liu JF, Wang JC. Nonhistone proteins HMG1 and HMG2 change the DNA helical structure. Science. 1978;199:1345–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Bustin M, Lehn DA, Landsman D. Structural features of the HMG chromosomal proteins and their genes. Biochim Biophys Acta. 1990;1049:231–43.CrossRefPubMedGoogle Scholar
  3. 3.
    Vaccari T, Beltrame M, Ferrari S, Bianchi ME. Hmg4, a new member of the Hmg1/2 gene family. Genomics. 1998;49:247–52.CrossRefPubMedGoogle Scholar
  4. 4.
    Goodwin GH, Sanders C, Johns EWA. New group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem. 1973;38:14–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Ferrari S, Finelli P, Rocchi M, Bianchi ME. The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13. Genomics. 1996;35:367–71.CrossRefPubMedGoogle Scholar
  6. 6.
    Yang EJ, Lee W, SK K, Song KS, Bae JS. Anti-inflammatory activities of oleanolic acid on HMGB1 activated HUVECs. Food Chem Toxicol. 2012;50:1288–94.CrossRefPubMedGoogle Scholar
  7. 7.
    Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248–51.CrossRefPubMedGoogle Scholar
  8. 8.
    O'Connor KA, Hansen MK, Rachal Pugh C, Deak MM, Biedenkapp JC, Milligan ED, Johnson JD, Wang H, Maier SF, Tracey KJ, Watkins LR. Further characterization of high mobility group box 1 (HMGB1) as a proinflammatory cytokine: central nervous system effects. Cytokine. 2003;24:254–65.CrossRefPubMedGoogle Scholar
  9. 9.
    Guazzi S, Strangio A, Franzi AT, Bianchi ME. HMGB1, an architectural chromatin protein and extracellular signalling factor, has a spatially and temporally restricted expression pattern in mouse brain. Gene Expr Patterns. 2003;3:29–33.CrossRefPubMedGoogle Scholar
  10. 10.
    van Zoelen MA, Laterre PF, van Veen SQ, van Till JW, Wittebole X, Bresser P, Tanck MW, Dugernier T, Ishizaka A, Boermeester MA, van der Poll T. Systemic and local high mobility group box 1 concentrations during severe infection. Crit Care Med. 2007;35:2799–804.CrossRefPubMedGoogle Scholar
  11. 11.
    Gaini S, Koldkjaer OG, Moller HJ, Pedersen C, Pedersen SSA. Comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study. Crit Care. 2007;11:R76.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Goldstein RS, Gallowitsch-Puerta M, Yang L, Rosas-Ballina M, Huston JM, Czura CJ, Lee DC, Ward MF, Bruchfeld AN, Wang H, Lesser ML, Church AL, Litroff AH, Sama AE, Tracey KJ. Elevated high-mobility group box 1 levels in patients with cerebral and myocardial ischemia. Shock. 2006;25:571–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Urbonaviciute V, Furnrohr BG, Meister S, Munoz L, Heyder P, De Marchis F, Bianchi ME, Kirschning C, Wagner H, Manfredi AA, Kalden JR, Schett G, Rovere-Querini P, Herrmann M, Voll RE. Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med. 2008;205:3007–18.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kuniyasu H, Chihara Y, Kondo H, Ohmori H, Ukai R. Amphoterin induction in prostatic stromal cells by androgen deprivation is associated with metastatic prostate cancer. Oncol Rep. 2003;10:1863–8.PubMedGoogle Scholar
  15. 15.
    Takada M, Hirata K, Ajiki T, Suzuki Y, Kuroda Y. Expression of receptor for advanced glycation end products (RAGE) and MMP-9 in human pancreatic cancer cells. Hepato-Gastroenterology. 2004;51:928–30.PubMedGoogle Scholar
  16. 16.
    Sasahira T, Akama Y, Fujii K, Kuniyasu H. Expression of receptor for advanced glycation end products and HMGB1/amphoterin in colorectal adenomas. Virchows Arch. 2005;446:411–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Nasiell K, Roger V, Nasiell M. Behavior of mild cervical dysplasia during long-term follow-up. Obstet Gynecol. 1986;67:665–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Petignat P, Roy M. Diagnosis and management of cervical cancer. BMJ. 2007;335:765–8.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Pinto AP, Crum CP. Natural history of cervical neoplasia: defining progression and its consequence. Clin Obstet Gynecol. 2000;43:352–62.CrossRefPubMedGoogle Scholar
  20. 20.
    Shastry BSSNP. impact on gene function and phenotype. Methods Mol Biol. 2009;578:3–22.CrossRefPubMedGoogle Scholar
  21. 21.
    Kornblit B, Munthe-Fog L, Madsen HO, Strom J, Vindelov L, Garred P. Association of HMGB1 polymorphisms with outcome in patients with systemic inflammatory response syndrome. Crit Care. 2008;12:R83.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wang Y, Li XP, Yin JY, Zhang Y, He H, Qian CY, Chen J, Zheng Y, Smieszkol K, YL F, Chen ZY, Zhou HH, Liu ZQ. Association of HMGB1 and HMGB2 genetic polymorphisms with lung cancer chemotherapy response. Clin Exp Pharmacol Physiol. 2014;41:408–15.CrossRefPubMedGoogle Scholar
  23. 23.
    Yue L, Zhang Q, He L, Zhang M, Dong J, Zhao D, Ma H, Pan H and Zheng L. Genetic predisposition of six well-defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population. J Cell Mol Med 2016;Google Scholar
  24. 24.
    Pang X, Zhang Y, Wei H, Zhang J, Luo Q, Huang C, Zhang S. Expression and effects of high-mobility group box 1 in cervical cancer. Int J Mol Sci. 2014;15:8699–712.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Yang SF, Yeh CB, Chou YE, Lee HL, Liu YF. Serpin peptidase inhibitor (SERPINB5) haplotypes are associated with susceptibility to hepatocellular carcinoma. Sci Rep. 2016;6:26605.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lin YS, Liu YF, Chou YE, Yang SF, Chien MH, CH W, Chou CH, Cheng CW, Wang PH. Correlation of chitinase 3-like 1 single nucleotide polymorphisms and haplotypes with uterine cervical cancer in Taiwanese women. PLoS One. 2014;9:e104038.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Kornblit B, Munthe-Fog L, Petersen SL, Madsen HO, Vindelov L, Garred P. The genetic variation of the human HMGB1 gene. Tissue Antigens. 2007;70:151–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Hernandez-Munain C, Krangel MS. Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors. Mol Cell Biol. 1994;14:473–83.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Chayka O, Kintscher J, Braas D, Klempnauer KH. v-Myb mediates cooperation of a cell-specific enhancer with the mim-1 promoter. Mol Cell Biol. 2005;25:499–511.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ahn MY, Kwon SM, Cheong HH, Park JH, Lee J, Min SK, Ahn SG, Yoon JH. Toll-like receptor 7 agonist, imiquimod, inhibits oral squamous carcinoma cells through apoptosis and necrosis. J Oral Pathol Med. 2012;41:540–6.PubMedGoogle Scholar
  31. 31.
    Flohr AM, Rogalla P, Meiboom M, Borrmann L, Krohn M, Thode-Halle B, Bullerdiek J. Variation of HMGB1 expression in breast cancer. Anticancer Res. 2001;21:3881–5.PubMedGoogle Scholar
  32. 32.
    Liu Y, Xie C, Zhang X, Huang D, Zhou X, Tan P, Qi L, Hu G, Tian Y, Qiu Y. Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance. Eur J Cancer. 2010;46:3007–15.CrossRefPubMedGoogle Scholar
  33. 33.
    Kornblit B, Masmas T, Petersen SL, Madsen HO, Heilmann C, Schejbel L, Sengelov H, Muller K, Garred P, Vindelov L. Association of HMGB1 polymorphisms with outcome after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2010;16:239–52.CrossRefPubMedGoogle Scholar
  34. 34.
    Mantovani RA. Survey of 178 NF-Y binding CCAAT boxes. Nucleic Acids Res. 1998;26:1135–43.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Mailly F, Berube G, Harada R, Mao PL, Phillips S, Nepveu A. The human cut homeodomain protein can repress gene expression by two distinct mechanisms: active repression and competition for binding site occupancy. Mol Cell Biol. 1996;16:5346–57.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lipsick JS, Wang DM. Transformation by v-Myb. Oncogene. 1999;18:3047–55.CrossRefPubMedGoogle Scholar
  37. 37.
    Ness SA. The Myb oncoprotein: regulating a regulator. Biochim Biophys Acta. 1996;1288:F123–39.PubMedGoogle Scholar
  38. 38.
    IH O, Reddy EP. The myb gene family in cell growth, differentiation and apoptosis. Oncogene. 1999;18:3017–33.CrossRefGoogle Scholar
  39. 39.
    De Marzo AM, Marchi VL, Epstein JI, Nelson WG. Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol. 1999;155:1985–92.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Supic G, Kozomara R, Zeljic K, Stanimirovic D, Magic M, Surbatovic M, Jovic N, Magic Z. HMGB1 genetic polymorphisms in oral squamous cell carcinoma and oral lichen planus patients. Oral Dis. 2015;21:536–43.CrossRefPubMedGoogle Scholar
  41. 41.
    Shifman S, Bronstein M, Sternfeld M, Pisante-Shalom A, Lev-Lehman E, Weizman A, Reznik I, Spivak B, Grisaru N, Karp L, Schiffer R, Kotler M, Strous RD, Swartz-Vanetik M, Knobler HY, Shinar E, Beckmann JS, Yakir B, Risch N, Zak NB, Darvasi A. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet. 2002;71:1296–302.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Xu Y, Chen Z, Zhang G, Xi Y, Sun R, Chai F, Wang X, Guo J, Tian L. HMGB1 overexpression correlates with poor prognosis in early-stage squamous cervical cancer. Tumour Biol. 2015;36:9039–47.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Hsin-Hung Wu
    • 1
    • 2
    • 3
  • Yu-Fan Liu
    • 4
    • 5
  • Shun-Fa Yang
    • 1
    • 5
  • Wea-Lung Lin
    • 6
    • 7
  • Shiuan-Chih Chen
    • 1
    • 6
    • 8
  • Chih-Ping Han
    • 6
    • 7
    • 9
  • Hsiang-Ling Wang
    • 1
    • 10
  • Long-Yau Lin
    • 1
    • 6
    • 9
  • Po-Hui Wang
    • 1
    • 6
    • 9
  1. 1.Institute of MedicineChung Shan Medical UniversityTaichungTaiwan
  2. 2.Infertility CenterXiamen EMBO Hospital XiamenFujianChina
  3. 3.Reproductive Medicine CenterKinmen HospitalKinmenTaiwan
  4. 4.Department of Biomedical SciencesChung Shan Medical UniversityTaichungTaiwan
  5. 5.Department of Medical ResearchChung Shan Medical University HospitalTaichungTaiwan
  6. 6.School of MedicineChung Shan Medical UniversityTaichungTaiwan
  7. 7.Department of PathologyChung Shan Medical University HospitalTaichungTaiwan
  8. 8.Department of Family and Community MedicineChung Shan Medical University HospitalTaichungTaiwan
  9. 9.Department of Obstetrics and GynecologyChung Shan Medical University HospitalTaichungTaiwan
  10. 10.Department of Beauty ScienceNational Taichung University of Science and TechnologyTaichungTaiwan

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