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A pooled multisite analysis of the effects of female reproductive hormones on glioma risk

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Abstract

Purpose

The association between female reproductive factors and glioma risk is unclear, but most published studies have been limited by small sample size. We conducted a pooled multisite study of pre- and postmenopausal women, investigating the effect of female reproductive factors, including hormonal medications.

Methods

Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (95 % CIs) assessing the effects of female reproductive factors and female hormonal medications in glioma cases and unrelated controls.

Results

Menarche over the age of 15 as compared to under 12 was associated with a statistically significant risk for glioma (OR 2.00, 95 % CI 1.47–2.71). Use of oral contraceptive pills (OCP) was inversely associated with risk of glioma (OR 0.61, 95 % CI 0.50–0.74), and there was an inverse trend with longer duration of OCP use (p for trend <0.0001). Use of hormone replacement therapy (HRT) was also inversely associated with risk of glioma (OR 0.55, 95 % CI 0.44–0.68), and there was an inverse trend with longer duration of use (p for trend <0.0001). Compared to those reporting neither OCP use nor HRT use, those who reported using both were less likely to have a diagnosis of glioma (OR 0.34, 95 % CI 0.24–0.48).

Conclusions

Female reproductive hormones may decrease the risk for glioma. The association appears to be strongest with greater length of use and use of both HRT and OCP.

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References

  1. Ostrom QT, Gittleman H, Farah P et al (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States 2006–2010. Neuro-Oncol 15(Suppl 2):ii1–ii56

    Article  PubMed  Google Scholar 

  2. Preston DL, Ron E, Yonehara S, Kobuke T, Fujii H, Kishikawa M et al (2002) Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure. J Natl Cancer Inst 94:1555–1563

    Article  CAS  PubMed  Google Scholar 

  3. Yonehara S, Brenner AV, Kishikawa M, Inskip PD, Preston DL, Ron E et al (2004) Clinical and epidemiologic characteristics of first primary tumors of the central nervous system and related organs among atomic bomb survivors in Hiroshima and Nagasaki, 1958–1995. Cancer 101:1644–1654

    Article  PubMed  Google Scholar 

  4. Garcia-Segura LM, Azocoitia I, DonCarlos LL (2001) Neuroprotection by estradiol. Prog Neurobiol 63:29–60

    Article  CAS  PubMed  Google Scholar 

  5. Santagati S, Melcangi RC, Celotti F, Martini L, Maggi A (1994) Estrogen receptor is expressed in different types of glial cells in culture. J Neurochem 63:2058–2064

    Article  CAS  PubMed  Google Scholar 

  6. Carroll RS, Zhang J, Dashner K, Sar M, Black PM (1995) Steroid hormone receptors in astrocytic neoplasms. Neurosurgery 37:496–503

    Article  CAS  PubMed  Google Scholar 

  7. Khalid MH, Shibata S, Furukawa K, Nadel A, Ammerman MD, Caputy AJ (2004) Role of estrogen receptor-related antigen in initiating the growth of human glioma cells. J Neurosurg 100:923–930

    Article  CAS  PubMed  Google Scholar 

  8. Hatch EE, Linet MS, Zhang J, Fine HA, Shapiro WR, Selker RG et al (2005) Reproductive and hormonal factors and risk of brain tumors in adult females. Int J Cancer 114:797–805

    Article  CAS  PubMed  Google Scholar 

  9. Silvera SA, Miller AB, Rohan TE (2006) Hormonal and reproductive factors and risk of glioma: a prospective cohort study. Int J Cancer 118:1321–1324

    Article  CAS  PubMed  Google Scholar 

  10. Hochberg F, Toniolo P, Cole P (1990) Nonoccupational risk indicators of glioblastoma in adults. J Neuro-Oncol 8:55–60

    Article  CAS  Google Scholar 

  11. Cantor KP, Lynch CF, Johnson D (1993) Reproductive factors and risk of brain, colon, and other malignancies in Iowa (United States). Cancer Causes Control 4:505–511

    Article  CAS  PubMed  Google Scholar 

  12. Lambe M, Coogan P, Baron J (1997) Reproductive factors and the risk of brain tumors: a population-based study in Sweden. Int J Cancer 72:389–393

    Article  CAS  PubMed  Google Scholar 

  13. Schlehofer B, Blettner M, Preston-Martin S, Niehoff D, Wahrendorf J, Arslan A, Ahlbom A, Choi WN, Giles GG, Howe GR, Little J, Ménégoz F et al (1999) Role of medical history in brain tumor development. Results from the International Adult Brain Tumor Study. Int J Cancer 82:155–160

    Article  CAS  PubMed  Google Scholar 

  14. Huang K, Whelan EA, Ruder AM, Ward EM, Deddens JA, Davis-King KE et al (2004) Reproductive factors and risk of glioma in women. Cancer Epidemiol Biomarkers Prev 13:1583–1588

    PubMed  Google Scholar 

  15. Felini MJ, Olshan AF, Schroeder JC, Carozza SE, Miike R, Rice T, Wrensch M (2009) Reproductive factors and hormone use and risk of adult glioma. Cancer Causes Control 20:87–96

    Article  PubMed Central  PubMed  Google Scholar 

  16. Wigertz A, Lönn S, Mathiesen T, Ahlbom A, Hall P, Feychting M et al (2006) Risk of brain tumors associated with exposure to exogenous female sex hormones. Am J Epidemiol 164:629–636

    Article  PubMed  Google Scholar 

  17. Benson VS, Pirie K, Green J, Casabonne D, Beral V, Million Women Study Collaborators (2008) Lifestyle factors and primary glioma and meningioma tumors in the Million Women Study cohort. Br J Cancer 99:185–190

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Wigertz A, Lönn S, Hall P, Auvinen A, Christensen HC, Johansen C, Klaeboe L, Salminen T, Schoemaker MJ, Swerdlow AJ, Tynes T, Feychting M (2008) Reproductive factors and risk of meningioma and glioma. Cancer Epidemiol Biomarkers Prev 17:2663–2670

    Article  PubMed  Google Scholar 

  19. Schlehofer B, Blettner M, Wahrendorf J (1992) Association between brain tumors and menopausal status. J Natl Cancer Inst 84:1346–1349

    Article  CAS  PubMed  Google Scholar 

  20. Qi Z, Shao C, Zhang X, Hui G, Zhong W (2013) Exogenous and endogenour hormones in relation to glioma in women: a meta-analysis of 11 case–control studies. PLoS ONE 8(7):e68695

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Kabat GC, Park Y, Hollenbeck AR, Schatzkin A, Rohan TE (2011) Reproductive factors and exogenous hormone use and risk of adult glioma in women in the NIH-AARP Diet and Health Study. Int J Cancer 128(4):944–950. doi:10.1002/ijc.25413

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Amirian E, Scheurer ME, Bondy ML (2010) The association between birth order, sibship size and glioma development in adulthood. Int J Cancer 126:2752–2756

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Wiemels JL, Wiencke JK, Kelsey KT, Moghadassi M, Rice T, Urayama KY et al (2007) Allergy-related polymorphisms influence glioma status and serum IgE levels. Cancer Epidemiol Biomarkers Prev 16:1229–1235

    Article  CAS  PubMed  Google Scholar 

  24. Wrensch M, McMillan A, Wiencke J, Wiemels J, Kelsey K, Patoka J et al (2007) Nonsynonymous coding single-nucleotide polymorphisms spanning the genome in relation to glioblastoma survival and age at diagnosis. Clin Cancer Res 13:197–205

    Article  CAS  PubMed  Google Scholar 

  25. Zisakis A, Piperi C, Themistocleous MS, Korkolopoulou P, Boviatsis EI, Sakas DE et al (2007) Comparative analysis of peripheral and localised cytokine secretion in glioblastoma patients. Cytokine 39:99–105

    Article  CAS  PubMed  Google Scholar 

  26. Berger A (2000) Th1 and Th2 responses: what are they? BMJ 321:424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Brandacher G, Winkler C, Schroecksnadel K, Margreiter R, Fuchs D (2006) Antitumoral activity of interferon-gamma involved in impaired immune function in cancer patients. Curr Drug Metab 7:599–612

    Article  CAS  PubMed  Google Scholar 

  28. Schwartzbaum J, Jonsson F, Ahlbom A, Preston-Martin S, Lönn S, Söderberg KC et al (2003) Cohort studies of association between self-reported allergic conditions, immune-related diagnoses and glioma and meningioma risk. Int J Cancer 106:423–428

    Article  CAS  PubMed  Google Scholar 

  29. Girón-González JA, Moral FJ, Elvira J, García-Gil D, Guerrero F, Gavilán I et al (2000) Consistent production of a higher TH1:TH2 cytokine ratio by stimulated T cells in men compared with women. Eur J Endocrinol 143:31–36

    Article  PubMed  Google Scholar 

  30. Subramanian S, Matejuk A, Zamora A, Vandenbark AA, Offner H (2003) Oral feeding with ethinyl estradiol suppresses and treats experimental autoimmune encephalomyelitis in SJL mice and inhibits the recruitment of inflammatory cells into the central nervous system. J Immunol 170:1548–1555

    Article  CAS  PubMed  Google Scholar 

  31. Vural P, Akgul C, Canbaz M (2006) Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women. Pharmacol Res 54:298–302

    Article  CAS  PubMed  Google Scholar 

  32. Kamada M, Irahara M, Maegawa M, Ohmoto Y, Murata K, Yasui T et al (2001) Transient increase in the levels of T-helper 1 cytokines in postmenopausal women and the effects of hormone replacement therapy. Gynecol Obstet Invest 52:82–88

    Article  CAS  PubMed  Google Scholar 

  33. Kumru S, Yildiz FM, Godekmerdan A, Kutlu S, Yilmaz B, Gurates B (2008) Effects of raloxifene and hormone replacement therapy on serum Th2 and Th3 type cytokine concentrations in healthy postmenopausal women: a randomised controlled trial. Arch Gynecol Obstet 277:489–493

    Article  CAS  PubMed  Google Scholar 

  34. Batistatou A, Stefanou D, Goussia A, Arkoumani E, Papavassiliou AG, Agnantis NJ (2004) Estrogen receptor beta (ERbeta) is expressed in brain astrocytic tumors and declines with dedifferentiation of the neoplasm. J Cancer Res Clin Oncol 130:405–410

    Article  CAS  PubMed  Google Scholar 

  35. Batistatou A, Kyzas PA, Goussia A, Arkoumani E, Voulgaris S, Polyzoidis K et al (2006) Estrogen receptor beta (ERbeta) protein expression correlates with BAG-1 and prognosis in brain glial tumours. J Neurooncol 77:17–23

    Article  CAS  PubMed  Google Scholar 

  36. Gonzalez-Aguero G, Ondarza R, Gamboa-Dominguez A, Cerbon MA, Camacho-Arroyo I (2001) Progesterone receptor isoforms expression pattern in human astrocytomas. Brain Res Bull 56:43–48

    Article  CAS  PubMed  Google Scholar 

  37. Inoue T, Akahira J, Suzuki T, Darnel AD, Kaneko C, Takahashi K et al (2002) Progesterone production and actions in the human central nervous system and neurogenic tumors. J Clin Endocrinol Metab 87:5325

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The Brain Tumor Epidemiology Consortium (BTEC) was instrumental in facilitating the collaboration and data sharing necessary for this study. In addition, the following individuals are acknowledged for their contributions: MD Anderson: Phyllis Adatto; University of Illinois at Chicago/Duke Study: Candace Zahora, Kristin Rankin, North Shore University Health System: Pat Lada, and Nicholas Vick; University of California at San Francisco: Lucie McCoy and Terri Rice. Research at the University of Illinois at Chicago was conducted under a Brain Tumor SPORE grant project (NIH Specialized Programs of Research Excellence grant 5P50 CA108786-4), directed by Dr. Faith Davis, Dr. Darell Bigner and Dr. Francis Ali-Osman. Funding was also received from the American Brain Tumor Association. Data from MD Anderson Cancer Center were collected under NIH grant R01CA070917 (M. Bondy, PI). M. E. Scheurer was funded by NIH grant K07CA131505. Data from UCSF were collected with funding from R01CA52689 and P50CA097257.

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Correspondence to Bhuma Krishnamachari.

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Krishnamachari, B., Il’yasova, D., Scheurer, M.E. et al. A pooled multisite analysis of the effects of female reproductive hormones on glioma risk. Cancer Causes Control 25, 1007–1013 (2014). https://doi.org/10.1007/s10552-014-0400-8

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  • DOI: https://doi.org/10.1007/s10552-014-0400-8

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