Skip to main content

Advertisement

Log in

Pooled analysis of the association of PTGS2 rs5275 polymorphism and NSAID use with invasive ovarian carcinoma risk

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Inflammation is postulated to play an important role in ovarian carcinogenesis. Prostaglandin endoperoxide synthase 2 (PTGS2) is responsible for the conversion of arachidonic acid to prostaglandins in response to inflammation. In a pooled analysis of two population-based studies, the Hawaii Ovarian Cancer Case–Control Study and the New England Case–Control Study, including 1,025 women with invasive ovarian carcinoma and 1,687 cancer-free controls, the association of ovarian cancer risk with the PTGS2 rs5275 polymorphism and the use of nonsteroidal antiinflammatory drugs (NSAIDs) were examined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. In the pooled analysis, the CC genotype was associated with a reduced risk of nonserous ovarian carcinoma (OR = 0.66; CI: 0.44–0.98). In addition, the lowest risk was observed among carriers of the CC genotype who were users of only nonaspirin NSAIDs (OR = 0.43; CI:0.20–0.93) in all women combined. The association of PTGS2 rs5275 with nonserous ovarian carcinoma and possible effect modification by NSAID use needs further validation, preferably in prospective studies.

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

Access this article

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. Auersperg N, Wong AS, Choi KC, Kang SK, Leung PC (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22(2):255–288

    Article  CAS  PubMed  Google Scholar 

  2. Fathalla MF (1971) Incessant ovulation—a factor in ovarian neoplasia? Lancet 2(7716):163

    Article  CAS  PubMed  Google Scholar 

  3. Espey LL (1994) Current status of the hypothesis that mammalian ovulation is comparable to an inflammatory reaction. Biol Reprod 50(2):233–238

    Article  CAS  PubMed  Google Scholar 

  4. Richards JS, Russell DL, Ochsner S, Espey LL (2002) Ovulation: new dimensions and new regulators of the inflammatory-like response. Annu Rev Physiol 64:69–92

    Article  CAS  PubMed  Google Scholar 

  5. Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90(17):7915–7922

    Article  CAS  PubMed  Google Scholar 

  6. Hofseth LJ, Ying L (2006) Identifying and defusing weapons of mass inflammation in carcinogenesis. Biochim Biophys Acta 1765(1):74–84

    CAS  PubMed  Google Scholar 

  7. Schildkraut JM, Moorman PG, Halabi S, Calingaert B, Marks JR, Berchuck A (2006) Analgesic drug use and risk of ovarian cancer. Epidemiology 17(1):104–107

    Article  PubMed  Google Scholar 

  8. Prizment AE, Folsom AR, Anderson KE (2010) Nonsteroidal anti-inflammatory drugs and risk for ovarian and endometrial cancers in the Iowa Women’s Health Study. Cancer Epidemiol Biomarkers Prev 19(2):435–442

    Article  CAS  PubMed  Google Scholar 

  9. Tzonou A, Polychronopoulou A, Hsieh CC, Rebelakos A, Karakatsani A, Trichopoulos D (1993) Hair dyes, analgesics, tranquilizers and perineal talc application as risk factors for ovarian cancer. Int J Cancer 55(3):408–410

    Article  CAS  PubMed  Google Scholar 

  10. Cramer DW, Harlow BL, Titus-Ernstoff L, Bohlke K, Welch WR, Greenberg ER (1998) Over-the-counter analgesics and risk of ovarian cancer. Lancet 351(9096):104–107

    Article  CAS  PubMed  Google Scholar 

  11. Akhmedkhanov A, Toniolo P, Zeleniuch-Jacquotte A, Kato I, Koenig KL, Shore RE (2001) Aspirin and epithelial ovarian cancer. Prev Med 33(6):682–687

    Article  CAS  PubMed  Google Scholar 

  12. Lacey JV Jr, Sherman ME, Hartge P, Schatzkin A, Schairer C (2004) Medication use and risk of ovarian carcinoma: a prospective study. Int J Cancer 108(2):281–286

    Article  CAS  PubMed  Google Scholar 

  13. Tavani A, Gallus S, La VC, Conti E, Montella M, Franceschi S (2000) Aspirin and ovarian cancer: an Italian case-control study. Ann Oncol 11(9):1171–1173

    Article  CAS  PubMed  Google Scholar 

  14. Hannibal CG, Rossing MA, Wicklund KG, Cushing-Haugen KL (2008) Analgesic drug use and risk of epithelial ovarian cancer. Am J Epidemiol 167(12):1430–1437

    Article  PubMed  Google Scholar 

  15. Pinheiro SP, Tworoger SS, Cramer DW, Rosner BA, Hankinson SE (2009) Use of nonsteroidal antiinflammatory agents and incidence of ovarian cancer in 2 large prospective cohorts. Am J Epidemiol 169(11):1378–1387

    Article  PubMed  Google Scholar 

  16. Crew KD, Neugut AI (2006) Aspirin and NSAIDs: effects in breast and ovarian cancers. Curr Opin Obstet Gynecol 18(1):71–75

    Article  PubMed  Google Scholar 

  17. Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271(52):33157–33160

    Article  CAS  PubMed  Google Scholar 

  18. DuBois RN, Abramson SB, Crofford L et al (1998) Cyclooxygenase in biology and disease. FASEB J 12(12):1063–1073

    CAS  PubMed  Google Scholar 

  19. Landen CN Jr, Mathur SP, Richardson MS, Creasman WT (2003) Expression of cyclooxygenase-2 in cervical, endometrial, and ovarian malignancies. Am J Obstet Gynecol 188(5):1174–1176

    Article  CAS  PubMed  Google Scholar 

  20. Shigemasa K, Tian X, Gu L, Shiroyama Y, Nagai N, Ohama K (2003) Expression of cyclooxygenase-2 and its relationship to p53 accumulation in ovarian adenocarcinomas. Int J Oncol 22(1):99–105

    CAS  PubMed  Google Scholar 

  21. Khalifeh I, Munkarah AR, Lonardo F et al (2004) Expression of Cox-2, CD34, Bcl-2, and p53 and survival in patients with primary peritoneal serous carcinoma and primary ovarian serous carcinoma. Int J Gynecol Pathol 23(2):162–169

    Article  PubMed  Google Scholar 

  22. Li S, Miner K, Fannin R, Carl BJ, Davis BJ (2004) Cyclooxygenase-1 and 2 in normal and malignant human ovarian epithelium. Gynecol Oncol 92(2):622–627

    Article  CAS  PubMed  Google Scholar 

  23. Cok SJ, Morrison AR (2001) The 3′-untranslated region of murine cyclooxygenase-2 contains multiple regulatory elements that alter message stability and translational efficiency. J Biol Chem 276(25):23179–23185

    Article  CAS  PubMed  Google Scholar 

  24. Dixon DA, Kaplan CD, McIntyre TM, Zimmerman GA, Prescott SM (2000) Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3′-untranslated region. J Biol Chem 275(16):11750–11757

    Article  CAS  PubMed  Google Scholar 

  25. Yang H, Gu J, Lin X et al (2008) Profiling of genetic variations in inflammation pathway genes in relation to bladder cancer predisposition. Clin Cancer Res 14(7):2236–2244

    Article  CAS  PubMed  Google Scholar 

  26. Cho KR, Shih I (2009) Ovarian cancer. Annu Rev Pathol 4:287–313

    Article  CAS  PubMed  Google Scholar 

  27. Mok SC, Kwong J, Welch WR et al (2007) Etiology and pathogenesis of epithelial ovarian cancer. Dis Markers 23(5–6):367–376

    CAS  PubMed  Google Scholar 

  28. Mandai M, Yamaguchi K, Matsumura N, Baba T, Konishi I (2009) Ovarian cancer in endometriosis: molecular biology, pathology, and clinical management. Int J Clin Oncol 14(5):383–391

    Article  PubMed  Google Scholar 

  29. Chiaffarino F, Parazzini F, Bosetti C et al (2007) Risk factors for ovarian cancer histotypes. Eur J Cancer 43(7):1208–1213

    Article  PubMed  Google Scholar 

  30. Gates MA, Rosner BA, Hecht JL, Tworoger SS (2010) Risk factors for epithelial ovarian cancer by histologic subtype. Am J Epidemiol 171(1):45–53

    Article  PubMed  Google Scholar 

  31. Berchuck A, Schildkraut JM, Pearce CL, Chenevix-Trench G, Pharoah PD (2008) Role of genetic polymorphisms in ovarian cancer susceptibility: development of an international ovarian cancer association consortium. Adv Exp Med Biol 622:53–67

    Article  PubMed  Google Scholar 

  32. Terry KL, De VI, Titus-Ernstoff L, Shih MC, Cramer DW (2005) Androgen receptor cytosine, adenine, guanine repeats, and haplotypes in relation to ovarian cancer risk. Cancer Res 65(13):5974–5981

    Article  CAS  PubMed  Google Scholar 

  33. Tung KH, Goodman MT, Wu AH et al (2003) Reproductive factors and epithelial ovarian cancer risk by histologic type: a multiethnic case-control study. Am J Epidemiol 158(7):629–638

    Article  PubMed  Google Scholar 

  34. Backlund MG, Mann JR, DuBois RN (2005) Mechanisms for the prevention of gastrointestinal cancer: the role of prostaglandin E2. Oncology 69(Suppl 1):28–32

    Article  CAS  PubMed  Google Scholar 

  35. Thun MJ (2000) Beyond willow bark: aspirin in the prevention of chronic disease. Epidemiology 11(4):371–374

    Article  CAS  PubMed  Google Scholar 

  36. Cook NR, Lee IM, Gaziano JM et al (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294(1):47–55

    Article  CAS  PubMed  Google Scholar 

  37. Awtry EH, Loscalzo J (2000) Aspirin. Circulation 101(10):1206–1218

    CAS  PubMed  Google Scholar 

  38. Cuzick J, Otto F, Baron JA et al (2009) Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 10(5):501–507

    Article  CAS  PubMed  Google Scholar 

  39. Potter JD (1999) Colorectal cancer: molecules and populations. J Natl Cancer Inst 91(11):916–932

    Article  CAS  PubMed  Google Scholar 

  40. Denkert C, Kobel M, Pest S et al (2002) Expression of cyclooxygenase 2 is an independent prognostic factor in human ovarian carcinoma. Am J Pathol 160(3):893–903

    CAS  PubMed  Google Scholar 

  41. Munkarah A, Ali-Fehmi R (2005) COX-2: a protein with an active role in gynecological cancers. Curr Opin Obstet Gynecol 17(1):49–53

    PubMed  Google Scholar 

  42. Ozel E, Pestereli HE, Simsek T, Erdogan G, Karaveli FS (2006) Expression of cyclooxygenase-2 and inducible nitric oxide synthase in ovarian surface epithelial carcinomas: is there any correlation with angiogenesis or clinicopathologic parameters? Int J Gynecol Cancer 16(2):549–555

    Article  CAS  PubMed  Google Scholar 

  43. Uddin S, Ahmed M, Hussain A et al (2010) Cyclooxygenase-2 inhibition inhibits PI3 K/AKT kinase activity in epithelial ovarian cancer. Int J Cancer 126(2):382–394

    Article  CAS  PubMed  Google Scholar 

  44. Seo SS, Song YS, Kang DH et al (2004) Expression of cyclooxygenase-2 in association with clinicopathological prognostic factors and molecular markers in epithelial ovarian cancer. Gynecol Oncol 92(3):927–935

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the physicians, administrators, and cancer registrars at the following institutions for their support of this study: Castle Memorial Hospital, Kaiser Foundation Hospital, Kapiolani Medical Center for Women and Children, Kuakini Medical Center, Queen’s Medical Center, Straub Clinic and Hospital, St Francis Hospital, Tripler Army Hospital, and Wahiawa General Hospital. We would also like to thank the NECC participants and their physicians. We are grateful to the family and friends of Kathryn Sladek Smith for their generous support of Ovarian Cancer Association Consortium through their donations to the Ovarian Cancer Research Fund. We thank Annette Lum-Jones and Ann Seifried for their assistance with genotyping. The findings and conclusions of this study do not necessarily represent the views of these physicians and institutions.

Financial Support

US Public Health Service grants R01-CA-58598, R01-CA-54419, P50-CA-105009, and contracts N01-CN-55424 and N01-PC-67001 from the National Cancer Institute, NIH, Department of Health and Human Services.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Galina Lurie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lurie, G., Terry, K.L., Wilkens, L.R. et al. Pooled analysis of the association of PTGS2 rs5275 polymorphism and NSAID use with invasive ovarian carcinoma risk. Cancer Causes Control 21, 1731–1741 (2010). https://doi.org/10.1007/s10552-010-9602-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-010-9602-x

Keywords

Navigation