Skip to main content
SpringerLink
Log in

Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38–8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76–4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24–1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  • Campa D, Hung RJ, Mates D et al (2005) Lack of association between 251 T > A polymorphism of IL8 and lung cancer risk. Cancer Epidemiol Biomarkers Prev 14:2457–2458

    Article  CAS  PubMed  Google Scholar 

  • Cheng YA, Shiue LF, Yu HS, Hsieh TY, Tsai CC (2000) Interleukin-8 secretion by cultured oral epidermoid carcinoma cells induced with nicotine and/or arecoline treatments. Kaohsiung J Med Sci 16:126–133

    CAS  PubMed  Google Scholar 

  • Dikshit R, Gupta PC, Ramasundarahettige C, Gajalakshmi V, Aleksandrowicz L, Badwe R et al (2012) Cancer mortality in India: a nationally representative survey. Lancet 379:1807–1816

    Article  PubMed  Google Scholar 

  • Gao LB, Pan XM, Jia J et al (2010) IL-8 -251A/T polymorphism is associated with decreased cancer risk among population based studies: evidence from a meta-analysis. Eur J Cancer 46:1333–1343

    Article  CAS  PubMed  Google Scholar 

  • Gu WL, Yang JJ (2011) Expression and clinical significance of serum interleukin-8 level in patients with oral squamous cell carcinoma. Shanghai Kou Qiang Yi Xue 20:78–81

    CAS  PubMed  Google Scholar 

  • Gunter MJ, Canzian F, Landi S, Chanock SJ, Sinha R, Rothman N (2006) Inflammation-related gene polymorphisms and colorectal adenoma. Cancer Epidemiol Biomarkers Prev 15:1126–1131

    Article  CAS  PubMed  Google Scholar 

  • Huang Q, Wang C, Qiu LJ, Shao F, Yu JH (2011) IL-8-251A > T polymorphism is associated with breast cancer risk: a meta-analysis. J Cancer Res Clin Oncol 137:1147–1150

    Article  CAS  PubMed  Google Scholar 

  • Hull J, Thomson A, Kwiatkowski D (2000) Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax 55:1023–1027

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kietthubthew S, Wickliffe J, Sriplung H, Ishida T, Chonmaitree T, Au WW (2010) Association of polymorphisms in proinflammatory cytokine genes with the development of oral cancer in Southern Thailand. Int J Hyg Environ Health 213:146–152

    Article  CAS  PubMed  Google Scholar 

  • Kim SJ, Uehara H, Karashima T, McCarty M, Shih N, Fidler IJ (2001) Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and metastasis of human prostate cancer cells implanted orthotopically in nude mice. Neoplasia 3:33–42

    Article  CAS  PubMed  Google Scholar 

  • Kotani N, Kudo R, Sakurai Y et al (2004) Cerebrospinal fluid interleukin 8 concentrations and the subsequent development of postherpetic neuralgia. Am J Med 116:318–324

    Article  CAS  PubMed  Google Scholar 

  • Landi S, Moreno V, Gioia-Patricola L et al (2003) Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activated receptor gamma with colorectal cancer. Cancer Res 63:3560–3566

    CAS  PubMed  Google Scholar 

  • Lee WP, Tai DI, Lan KH et al (2005) The -251T allele of the interleukin-8 promoter is associated with increased risk of gastric carcinoma featuring diffuse-type histopathology in Chinese population. Clin Cancer Res 11:6431–6441

    Article  CAS  PubMed  Google Scholar 

  • Li A, Varney ML, Singh RK (2001) Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials. Clin Cancer Res 7:3298–3304

    CAS  PubMed  Google Scholar 

  • Li K, Yao S, Liu S, Wang B, Mao D (2009) Genetic polymorphisms of interleukin 8 and risk of ulcerative colitis in the Chinese population. Clinica Chimica Acta 405:30–34

    Article  CAS  Google Scholar 

  • Lin PY, Yu CH, Wang JT, Chen HH, Cheng SJ, Kuo MY, Chiang CP (2008) Expression of hypoxiainducible factor-1 alpha is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan. J Oral Pathol Med 37:18–25

    Article  PubMed  Google Scholar 

  • Liu CM, Yeh CJ, Yu CC et al (2012) Impact of interleukin-8 gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan. Oral Dis 18:307–314

    Article  PubMed  Google Scholar 

  • Lokshin AE, Winans M, Landsittel D et al (2006) Circulating IL-8 and anti- IL-8 autoantibody in patients with ovarian cancer. Gynecol Oncol 102:244–251

    Article  CAS  PubMed  Google Scholar 

  • Mallath MK, Taylor DG, Badwe RA, Rath GK, Shanta V, Pramesh CS et al (2014) The growing burden of cancer in India: epidemiology and social context. Lancet Oncol 15:e205–e212

    Article  PubMed  Google Scholar 

  • McCarron SL, Edwards S, Evans PR et al (2002) Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res 62:3369–3372

    CAS  PubMed  Google Scholar 

  • Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nagaraj NS, Beckers S, Mensah JK, Waigel S, Vigneswaran N, Zacharias W (2006) Cigarette smoke condensate induces cytochromes P450 and aldo-keto reductases in oral cancer cells. Toxicol Lett 165:182–194

    Article  CAS  PubMed  Google Scholar 

  • Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL, Miller RJ (2001) Chemokines and glycoprotein 120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 21:5027–5035

    CAS  PubMed  Google Scholar 

  • Rafrafi A, Chahed B, Kaabachi S (2013) Association of IL-8 gene polymorphisms with non small cell lung cancer in Tunisia: a case control study. Human Immunol 74:1368–1374

    Article  CAS  Google Scholar 

  • Reyes-Gibby CC, Spitz M, Wu X et al (2007) Cytokine genes and pain severity in lung cancer: exploring the influence of TNF-{alpha}-308 G/A IL6–174G/C and IL8–251T/A. Cancer Epidemiol Biomarkers Prev 16:2745–2751

    Article  CAS  PubMed  Google Scholar 

  • Reyes-Gibby CC, Shete S, Yennurajalingam S et al (2009) Genetic and non genetic covariates of pain severity in patients with adenocarcinoma of the pancreas: assessing the influence of cytokine genes. J Pain Symptom Manag 38:894–902

    Article  CAS  Google Scholar 

  • Savage SA, Abnet CC, Mark SD et al (2004) Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 13:2251–2257

    CAS  PubMed  Google Scholar 

  • Savage SA, Hou L, Lissowska J, Chow WH, Zatonski W, Chanock SJ, Yeager M (2006) Interleukin-8 polymorphisms are not associated with gastric cancer risk in a Polish population. Cancer Epidemiol Biomarkers Prev 15:589–591

    Article  CAS  PubMed  Google Scholar 

  • Shimizu Y, Kondo S, Shirai A, Furukawa M, Yoshizaki T (2008) A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer. Auris Nasus Larynx 35:381–389

    Article  PubMed  Google Scholar 

  • Srivastava S, Salim N, Robertson MJ (2010) Interleukin-18: biology and role in the immunotherapy of cancer. Curr Med Chem 17:3353–3357

    Article  CAS  PubMed  Google Scholar 

  • Wang N, Zhou R, Wang C, Guo X, Chen Z, Yang S, Li Y (2012) 251 T/A polymorphism of the interleukin-8 gene and cancer risk: a huge review and meta-analysis based on 42 case–control studies. Mol Biol Rep 39:2831–2841

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Wang C, Zhao Z, Liu F, Guan X, Lin X, Zhang L (2013) Association between -251A > T polymorphism in the interleukin-8 gene and oral cancer risk: a meta-analysis. Gene 522:168–176

    Article  CAS  PubMed  Google Scholar 

  • Watanabe H, Iwase M, Ohashi M, Nagumo M (2002) Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines. Oral Oncol 38:670679

    Article  Google Scholar 

  • Watkins LR, Wiertelak EP, Goehler LE, Smith KP, Martin D, Maier SF (1994) Characterization of cytokine-induced hyperalgesia. Brain Res 654:15–26

    Article  CAS  PubMed  Google Scholar 

  • Watkins LR, Maier SF, Goehler LE (1995) Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 63:289–302

    Article  CAS  PubMed  Google Scholar 

  • 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:e28083

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financially supported by a grant from Indian Council of Medical Research (ICMR) (No: 3/2/2/131/2012/NCD-III).

Author information

Authors and Affiliations

  1. Department of Anaesthesiology, King George’s Medical University, Lucknow, UP, India

    Prithvi Kumar Singh, Girish Chandra, Jaishri Bogra & Rajni Gupta

  2. Department of Surgical Oncology, King George’s Medical University, Lucknow, UP, India

    Vijay Kumar

  3. Department of Biochemistry, King George’s Medical University, Lucknow, UP, 226003, India

    Syed Rizwan Hussain, Abbas Ali Mahdi & Mohammad Kaleem Ahmad

  4. Department of Microbiology, King George’s Medical University, Lucknow, UP, India

    Amita Jain

Authors
  1. Prithvi Kumar Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Girish Chandra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jaishri Bogra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajni Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vijay Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Syed Rizwan Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amita Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Abbas Ali Mahdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mohammad Kaleem Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Kaleem Ahmad.

Ethics declarations

Conflict of interest

The authors have no conflict of interests in this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, P.K., Chandra, G., Bogra, J. et al. Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain. Biochem Genet 54, 95–106 (2016). https://doi.org/10.1007/s10528-015-9704-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-015-9704-y

Keywords

Search

Navigation