Lack of Association of a Common Polymorphism in the 3'-UTR of Interleukin 8 with Non Small Cell Lung Cancer in Kashmir

  • Bhat, Imtiyaz Ahmad (Department of Immunology and Molecular Medicine, Sher i Kashmir institute of Medical Sciences Srinagar) ;
  • Pandith, Arshid A. (Advanced Center for Human Genetics, Sher i Kashmir institute of Medical Sciences Srinagar) ;
  • Bhat, Bashir A. (Department of Plastic Surgery, Sher i Kashmir institute of Medical Sciences Srinagar) ;
  • Naykoo, Niyaz A. (Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir) ;
  • Qasim, Iqbal (Department of Immunology and Molecular Medicine, Sher i Kashmir institute of Medical Sciences Srinagar) ;
  • Rasool, Roohi (Department of Immunology and Molecular Medicine, Sher i Kashmir institute of Medical Sciences Srinagar) ;
  • Aziz, Sheik Aejaz (Department of Medical Oncology, Sher i Kashmir institute of Medical Sciences Srinagar) ;
  • Shah, Zafar Amin (Department of Immunology and Molecular Medicine, Sher i Kashmir institute of Medical Sciences Srinagar)
  • Published : 2013.07.30


Background: Chronic inflammation is considered as an important factor in the pathogenesis of lung cancer. The presence of inflammatory cells and higher levels of pro-inflammatory cytokines in the tumor microenvironment and their surrounding tissues is gaining much importance in research. Materials and Methods: One hundred ninety NSCLC cases and 200 age, smoking and sex matched controls were evaluated for association of IL-8 -251 (rs4073) and IL-8 -845 (rs2227532) in our population. Restriction fragment length polymorphism (RFLP) was used followed by direct sequencing for the detection of SNPs. Results: The IL-8 -845 polymorphism was not found in our population. No significant association was observed between the IL-8 -251 AT genotypes and IL-8 -25 AA genotypes and NSCLC (p=0.05) in our population. The IL-8 -251 A allele was also non-significant (p=0.05) in NSCLC patients. Conclusions: In conclusion, this report reveals lack of association between IL-8 - 251 A/T polymorphism and NSCLC in our Kashmir Valley population.


Interleukin 8;restriction fragment length polymorphism;non small cell lung cancer (NSCLC)


  1. Andia DC, de Oliveira NF, Letra AM, et al (2011). Interleukin-8 gene promoter polymorphism (rs4073) may contribute to chronic periodontitis. J Periodontol, 82, 893-9.
  2. Araki S, Omori Y, Lyn D, et al (2007). Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer. Cancer Res, 67, 6854-62.
  3. Balkwill F (2004). Cancer and the chemokine network. Nat Rev Cancer, 4, 540-50.
  4. Balkwill F, Mantovani A (2001). Inflammation and cancer: back to virchow? Lancet, 357, 539-45.
  5. Ben Nasr H, Chahed K, Mestiri S, et al (2007). Association of IL-8 (-251) T/A polymorphism with susceptibility to and aggressiveness of nasopharyngeal carcinoma. Hum Immunol, 68, 761-9.
  6. Bidwell J, Keen L, Gallagher G, et al (2001). Cytokine gene polymorphism in human disease: on-line databases, supplement 1. Genes Immun, 2, 61-70.
  7. Boffetta P, Ye W, Boman G, Nyren (2002). Lung cancer risk in a population-based cohort of patients hospitalized for asthma in Sweden. Eur Respir J, 19, 127-33.
  8. Brew R, Southern SA, Flanagan BF, McDicken IW, Christmas SE (1996). Detection of interleukin-8 mRNA and protein in human colorectal carcinoma cells. Eur J Cancer, 32, 2142-7.
  9. Campa D, Hung RJ, Mates D, et al (2005). Lack of association between -251 T>A polymorphism of IL-8 and lung cancer risk. Cancer Epidemiol Biomarkers Prev, 14, 2457-8.
  10. Campa D, Zienolddiny S, Maggini V, et al (2004). Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis, 2, 229-35.
  11. Cohen RF, Contrino J, Spiro JD, et al (1995). Interleukin-8 expression by head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg, 121, 202-9.
  12. Cohen BH, Diamond EL, Graves CG, et al (1977). A common familial component in lung cancer and chronic obstructive pulmonary disease. Lancet, 2, 523-6.
  13. Dan H, Liu W, Zhou Y, et al (2010). Association of Interleukin-8 gene polymorphisms and haplotypes with oral lichen planus in a Chinese population. Inflammation, 33, 76-81.
  14. Du H, Bay BH, Mahendran R, Olivo M (2002). Endogenous expression of interleukin-8, interleukin-10 in nasopharyngeal carcinoma cells, the effect of photodynamic therapy. Int J Mol Med, 10, 73-6.
  15. Gao LB, Pan XM, Jia J, et al (2010). IL-8 -251A/T polymorphism is associated with decreased cancer risk among populationbased studies: Evidence from a meta-analysis. Eur J Cancer, 46, 1333-43.
  16. Aggarwal BB, Vijayalekshmi RV, Sung B (2009). Targeting inflammatory pathways for prevetion and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res, 15, 425-30.
  17. Ahmed OI, Adel AM, Diab DR, Gobran NS (2006). Prognostic value of serum level of interleukin-6 and interleukin-8 in metastatic breast cancer patients. Egypt J Immunol, 13, 61-8.
  18. Hull J, Thomson A, Kwiatkowski D (2000). Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax, 55, 1023-7.
  19. Hu LX, Du YY, Zhang Y, Pan YY (2012). Lack of association between Interleukin-8-251 T>A polymorphism and colorectal cancer risk: a meta-analysis based on 3,019 cases and 3,984 controls. Asian Pac J Cancer Prev, 13, 5075-9.
  20. Lee EB, Kim JY, Zhao J (2007). Haplotype association of IL-8 gene with Behcet's disease. Tissue Antigens, 69, 128-32.
  21. Lee WP, Tai DI, Lan KH, et al (2005). The IL8 -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, 6431-41.
  22. 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. Clin Chem Acta, 405, 30-4.
  23. Lin WW, Karin M (2007). A cytokine mediated link between innate immunity, inflammation and cancer. J Clin Invest, 117, 1175-83.
  24. Lurje G, Zhang W, Schultheis AM, et al (2008). Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer. Ann Oncol, 19, 1734-41.
  25. Mantovani A (2009). Cancer related inflammation: the seven the hall mark of cancer. Am Soc Clin Oncol, 1092, 1-10.
  26. Mayne ST, Buenconsejo J, Janerich DT (1999). Previous lung disease and risk of lung cancer among men and women nonsmokers. Am J Epidemiol, 149, 13-20.
  27. McCarron SL, Edwards S, Evans PR, et al (2002). Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res, 62, 3369-72.
  28. Millar HJ, Nemeth JA, McCabe FL, Pikounis B, Wickstrom E (2008). Circulating human interleukin-8 as an indicator of cancer progression in a nude rat orthotopic human non-small cell lung carcinoma model. Cancer Epidemiol Biomarkers Prev, 17, 2180-7.
  29. Mukaida N, Shiroo M, Matsushima K (1989). Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol, 143, 1366-71.
  30. Mustapha MA, Shahpudin SN, Aziz AA, Ankathil R (2012). Risk modification of colorectal cancer susceptibility by interleukin-8 -251T>A polymorphism in Malaysians. World J Gastroenterol, 18, 2668-73.
  31. Ohyauchi M, Imatani A, Yonechi M, et al (2005). The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut, 54, 330-5.
  32. Peebles KA, Lee JM, Mao JT, et al (2007). Inflammation and lung carcinogenesis: applying findings in prevention and treatment. Expert Rev Anticancer Ther, 7, 1405-21.
  33. Qin X, Deng Y, Liao XC, et al (2012). The IL-8 gene polymorphisms and the risk of the hepatitis B virus/infected patients. DNA Cell Biol, 31, 1125-30.
  34. Shahzad A, Knapp M, Lang I, Kohler G (2010). Interleukin 8 (IL-8) - a universal biomarker. Int Arch Med, 3, 11.
  35. Song B, Zhang D, Wang S, Zheng H, Wang X (2009). Association of Interleukin-8 with cachexia from patients with low-third gastric cancer. Comp Funct Genomics, [Epub ahead of print].
  36. Taguchi A, Ohmiya N, Shirai K, et al (2005). Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol Biomarkers Prev, 14, 2487-93.
  37. Takizawa H, Tanaka M, Takami K, et al (2000). Increased expression of inflammatory mediators in small-airway epithelium from tobacco smokers. Am J Physiol Lung Cell Mol Physiol, 278, 906-13.
  38. Vicari AP, Caux C (2002). Chemokines in cancer. Cytokine Growth Factor Rev, 13, 143-54.Wang N, Zhou R, Wang C, et al (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, 2831-41.
  39. Wang Z, Wang C, Zhao Z, et al (2013). Association between -251A>T polymorphism in the interleukin-8 gene and oral cancer risk: a meta-analysis. Gene, 2, 168-76.
  40. Waugh DJ, Wilson C (2008). The Interleukin-8 pathway in cancer. Clin Cancer Res, 14, 6735-41.
  41. Wei YS, Lan Y, Tang RG, et al (2007). Single nucleotide polymorphism and haplotype association of the interleukin-8 gene with nasopharyngeal carcinoma. Clin Immunol, 125, 309-17.
  42. Xie K (2001). Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev, 12, 375-91.
  43. Xue H, Liu J, Lin B, et al (2012). A meta-analysis of Interleukin-8 -251 promoter polymorphism associated with gastric cancer risk. PLoS One, 7, 28083.

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