Skip to main content

Advertisement

SpringerLink
Log in

Cyclooxygenase-2 Polymorphisms and Breast Cancer Associated Risk in Pakistani Patients

  • Research
  • Published:
Pathology & Oncology Research

Abstract

Prostaglandins produced by Cyclooxygenase-2 enzyme have been implicated to have a role in breast carcinogenesis. Several single nucleotide polymorphisms (SNPs) linked to COX-2 enzyme are reported to modulate its expression. The aim of the present study was to examine association of these SNPs to breast cancer risk in Pakistani patients. Methods In this case–control study, three sequence variants rs689465, rs689466, rs20417 in the promoter region of COX-2 were screened to evaluate the association with breast cancer risk. A total of 150 breast cancer patients and 101 healthy control genomic DNA were genotyped for rs689456, rs689466, rs20417 and their genotypes distribution in cases and control were compared using Pearson chi square test. Risk association was analyzed through odd ratio calculated by logistic regression. Results A screening analysis of COX-2 SNPs in 101 healthy controls showed distribution of Minor allelic frequency distribution of SNPs as follows : rs689465 (0.12), rs689466 (0.15), rs20417 (0.23). Further analyses revealed that their observed genotype frequencies were consistent with Hardy Weinberg equilibrium and strong linkage disequilibrium was identified between rs20417, rs689465 and rs689466. The Combined allele variants analysis showed that Haplotype rs68965G- 689466A-20417C (OR 2.909; CI 95 %1.3776.327; P = 0.007) was significantly associated with breast cancer. Conclusions Our results indicate no strong association between three most frequent COX-2 SNPs rs689465 rs689466, rs20417 studied with breast cancer risk in the single locus analysis. However, our data suggested that combined COX-2 SNP haplotype have a role in breast cancer associated risk in Pakistani patients.

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

Similar content being viewed by others

References

  1. Rolland PH, Martin PM, Jacquemier J, Rolland AM, Toga M (1980) Prostaglandin in human breast cancer: Evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells. J Natl Cancer Inst 64:1061–1070

    CAS  PubMed  Google Scholar 

  2. Williams CS, DuBois RN (1996) Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 270:G393–400

    CAS  PubMed  Google Scholar 

  3. O’Neill GP, Ford-Hutchinson AW (1993) Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 330:156–160

    PubMed  Google Scholar 

  4. Herschman HR (1994) Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metastasis Rev 13:241–256

    Article  CAS  PubMed  Google Scholar 

  5. Bennett A, Charlier EM, McDonald AM, Simpson JS, Stamford IF, Zebro T (1977) Prostaglandins and breast cancer. Lancet 2:624–626

    Article  CAS  PubMed  Google Scholar 

  6. Half E, Tang XM, Gwyn K, Sahin A, Wathen K, Sinicrope FA (2002) Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. Cancer Res 62:1676–1681

    CAS  PubMed  Google Scholar 

  7. Hwang D, Scollard D, Byrne J, Levine E (1998) Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 90:455–460

    Article  CAS  PubMed  Google Scholar 

  8. Gong Z, Bostick RM, Xie D, Hurley TG, Deng Z, Dixon DA et al (2009) Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma. Int J Colorectal Dis 24:647–654

    Article  PubMed Central  PubMed  Google Scholar 

  9. Hu HM, Kuo CH, Lee CH, Wu IC, Lee KW, Lee JM, et al (2009) Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study. BMC Gastroenterol 9:37

  10. Hamajima N, Takezaki T, Matsuo K, Saito T, Inoue M, Hirai T, Kato T, Ozeki J, Tajima K (2001) Genotype Frequencies of Cyclooxygenase 2 (COX2) Rare Polymorphisms for Japanese with and without Colorectal Cancer. Asian Pac J Cancer Prev 2:57–62

    PubMed  Google Scholar 

  11. Appleby SB, Ristimaki A, Neilson K, Narko K, Hla T (1994) Structure of the human cyclo-oxy genase-2 gene. Biochem J 302:723–727

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Papafili A, Hill MR, Brull DJ, McAnulty RJ, Marshall RP, Humphries SE et al (2002) Common promoter variant in cyclooxygenase-2 represses gene expression: evidence of role in acute-phase inflammatory response. Arterioscler Thromb Vasc Biol 22:1631–1636

    Article  CAS  PubMed  Google Scholar 

  13. Zhang X, Miao X, Tan W, Ning B, Liu Z, Hong Y et al (2005) Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. Gastroenterology 129:565–576

    CAS  PubMed  Google Scholar 

  14. Szezekilik W, Sanak M, Szezeklik A (2004) Functional effects and gender association of COX-2 gene polymorphism G-765C in bronchial asthama. J Allergy Clin Immunol 114:248–253

    Article  Google Scholar 

  15. Zang X, Miao X, Tan W, Ning B, Liu Z, Hong Y (2005) Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of oseophageal cancer. Gastroenterolgy 129:565–576

    Google Scholar 

  16. Bhurgri Y (2004) The role of cancer registration in National Cancer Control Pakistan. J Pak Med Assoc 54:402–404

    CAS  PubMed  Google Scholar 

  17. Pereira C, Sousa H, Ferreira P, Fragoso M, Moreira-Dias L, Lopes C et al (2006) 765G > C COX-2 polymorphism may be a susceptibility marker for gastric adenocarcinoma in patients with atrophy or intestinal metaplasia. World J Gastroenterol 12:5473–5478

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Upadhyay R, Jain M, Kumar S, Ghoshal UC, Mittal B (2009) Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squamous cell carcinoma. Mutat Res 663:52–59

    Article  CAS  PubMed  Google Scholar 

  19. Piranda DN, Festa-Vasconcellos JS, Amaral LM, Bergmann A, Vianna-Jorge R (2010) Polymorphisms in regulatory regions of cyclooxygenase-2 gene and breast cancer risk in Brazilians: a case–control study. BMC Cancer 10:613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Ke-Da Y, Chen AX, Yang C, Qiu LX, Fan L, Xu WH et al (2010) Current evidence on the relationship between polymorphisms in the COX-2 gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 122:251–257

    Article  Google Scholar 

  21. Zhu W, Wei BB, Shan X, Liu P (2010) 765G > C and 8473 T > C polymorphisms of COX-2 and cancer risk: a meta-analysis based on 33 case–control studies. Mol Biol Rep 37:277–288

    Article  CAS  PubMed  Google Scholar 

  22. Ahmed F (1996) Pakistan: Ethnic fragmentation or national integration. Pak Dev Rev 35:631–645

    Google Scholar 

  23. Gao J, Ke Q, Ma HX, Wang Y, Zhou Y, Hu ZB, Zhai XJ, Wang XC, Qing JW, Chen WS et al (2007) Functional polymorphisms in the cyclooxygenase 2 (COX-2) gene and risk of breast cancer in a Chinese population. J Toxicol Environ Health A 70:908–915

    Article  PubMed  Google Scholar 

  24. Dossus L, Kaaks R, Canzian F, Albanes D, Berndt SI, Boeing H et al (2010) PTGS2 and IL6 genetic variation and risk of breast and prostate cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3). Carcinogenesis 31:455–461

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Wang X-f, Huang M-z, Zhang X-w, Hua R-x, Guo W-j, COX-2-765G (2013) C Polymorphism Increases the Risk of Cancer: A Meta-Analysis. PLoS ONE 8(9):e73213. doi:10.1371/journal.pone.0073213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Brasky TM, Bonner MR, Moysich KB, Ambrosone CB, Nie J, Tao MH et al (2011) Genetic variant in Cox-2, Non-steroidal anti-inflammatory drug and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study. Breast Cancer Res Treat 126:157–165

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Microbiology, The Aga Khan University, Stadium Road, Karachi, 74800, Pakistan

    Tariq Moatter & Shahid Pervez

  2. Department of Pathology, Baqai Medical University, Karachi, Pakistan

    Muniba Aban & Waseem Iqbal

Authors
  1. Tariq Moatter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muniba Aban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Waseem Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shahid Pervez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shahid Pervez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moatter, T., Aban, M., Iqbal, W. et al. Cyclooxygenase-2 Polymorphisms and Breast Cancer Associated Risk in Pakistani Patients. Pathol. Oncol. Res. 21, 97–101 (2015). https://doi.org/10.1007/s12253-014-9792-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-014-9792-8

Keywords

Search

Navigation