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Urinary melatonin and risk of ovarian cancer

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Abstract

Purpose

Melatonin has anti-carcinogenic properties, including modulation of estradiol production, cell cycle regulation, and promotion of apoptosis. Urinary melatonin has been inversely associated with breast cancer in some studies, but the association with ovarian cancer has not been investigated.

Methods

We measured urinary 6-sulfatoxymelatonin (aMT6s) in nested ovarian cancer case–control studies in the Nurses’ Health Study (NHS; n = 100 cases; 199 controls) and NHSII (n = 52 cases; 105 controls); samples were mainly from first morning voids. Controls were matched to cases on year of birth, menopause status, use of menopausal hormone therapy, and urine collection characteristics. We evaluated the association of tertiles of aMT6s, corrected for creatinine concentrations, with risk of ovarian cancer using conditional logistic regression. Models were adjusted for key ovarian cancer risk factors, and we additionally evaluated adjustment for usual sleep duration, snoring, and history of rotating night shift work.

Results

aMT6s was not significantly associated with risk of ovarian cancer. In multivariable models, the odds ratio comparing the highest tertile of aMT6s to the lowest was 0.79, 95 % confidence interval (CI) 0.40–1.56 in the NHS and 2.88, and 95 % CI in the NHSII 0.97–8.52. Additional adjustment for sleep habits and night shift work had little impact on the observed results. We observed no clear association between urinary melatonin and ovarian cancer risk.

Conclusions

These results are consistent with our previous study in which we reported no association between night shift work and ovarian cancer; however, given the small sample size in our study, additional evaluation in larger studies is warranted.

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References

  1. Straif K, Baan R, Grosse Y et al (2007) Carcinogenicity of shift-work, painting, and fire-fighting. Lancet Oncol. 8:1065–1066

    Article  PubMed  Google Scholar 

  2. Poole EM, Schernhammer ES, Tworoger SS (2011) Rotating night shift work and risk of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 20:934–938

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bhatti P, Cushing-Haugen KL, Wicklund KG, Doherty JA, Rossing MA (2013) Nightshift work and risk of ovarian cancer. Occup Environ Med 70:231–237

    Article  PubMed  PubMed Central  Google Scholar 

  4. Carter BD, Diver WR, Hildebrand JS, Patel AV, Gapstur SM (2014) Circadian disruption and fatal ovarian cancer. Am J Prev Med 46:S34–S41

    Article  PubMed  Google Scholar 

  5. Viswanathan AN, Schernhammer ES (2009) Circulating melatonin and the risk of breast and endometrial cancer in women. Cancer Lett 281:1–7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Anisimov VN (2006) Light pollution, reproductive function and cancer risk. Neuro Endocrinol Lett. 27:35–52

    CAS  PubMed  Google Scholar 

  7. Haus EL, Smolensky MH (2013) Shift work and cancer risk: potential mechanistic roles of circadian disruption, light at night, and sleep deprivation. Sleep Med Rev 17:273–284

    Article  PubMed  Google Scholar 

  8. Treeck O, Haldar C, Ortmann O (2006) Antiestrogens modulate MT1 melatonin receptor expression in breast and ovarian cancer cell lines. Oncol Rep 15:231–235

    CAS  PubMed  Google Scholar 

  9. Srinivasan V, Pandi-Perumal SR, Brzezinski A, Bhatnagar KP, Cardinali DP (2011) Melatonin, immune function and cancer. Recent Pat Endocr Metab Immune Drug Discov. 5:109–123

    Article  CAS  PubMed  Google Scholar 

  10. Futagami M, Sato S, Sakamoto T, Yokoyama Y, Saito Y (2001) Effects of melatonin on the proliferation and cis-diamminedichloroplatinum (CDDP) sensitivity of cultured human ovarian cancer cells. Gynecol Oncol 82:544–549

    Article  CAS  PubMed  Google Scholar 

  11. Shellard SA, Whelan RD, Hill BT (1989) Growth inhibitory and cytotoxic effects of melatonin and its metabolites on human tumour cell lines in vitro. Br J Cancer 60:288–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bartsch H, Buchberger A, Franz H et al (2000) Effect of melatonin and pineal extracts on human ovarian and mammary tumor cells in a chemosensitivity assay. Life Sci 67:2953–2960

    Article  CAS  PubMed  Google Scholar 

  13. Petranka J, Baldwin W, Biermann J, Jayadev S, Barrett JC, Murphy E (1999) The oncostatic action of melatonin in an ovarian carcinoma cell line. J Pineal Res 26:129–136

    Article  CAS  PubMed  Google Scholar 

  14. Papazisis KT, Kouretas D, Geromichalos GD et al (1998) Effects of melatonin on proliferation of cancer cell lines. J Pineal Res 25:211–218

    Article  CAS  PubMed  Google Scholar 

  15. Chuffa LG, Fioruci-Fontanelli BA, Mendes LO et al (2013) Characterization of chemically induced ovarian carcinomas in an ethanol-preferring rat model: influence of long-term melatonin treatment. PLoS ONE 8:e81676

    Article  PubMed  PubMed Central  Google Scholar 

  16. Moore CB, Siopes TD (2004) Spontaneous ovarian adenocarcinoma in the domestic turkey breeder hen (Meleagris gallopavo): effects of photoperiod and melatonin. Neuro Endocrinol Lett. 25:94–101

    CAS  PubMed  Google Scholar 

  17. Adriaens I, Jacquet P, Cortvrindt R, Janssen K, Smitz J (2006) Melatonin has dose-dependent effects on folliculogenesis, oocyte maturation capacity and steroidogenesis. Toxicology 228:333–343

    Article  CAS  PubMed  Google Scholar 

  18. Voordouw BC, Euser R, Verdonk RE et al (1992) Melatonin and melatonin–progestin combinations alter pituitary–ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 74:108–117

    CAS  PubMed  Google Scholar 

  19. Karasek M, Kowalski AJ, Zylinska K (2000) Serum melatonin circadian profile in women suffering from the genital tract cancers. Neuro Endocrinol Lett. 21:109–113

    CAS  PubMed  Google Scholar 

  20. Schernhammer ES, Hankinson SE (2005) Urinary melatonin levels and breast cancer risk. J Natl Cancer Inst 97:1084–1087

    Article  CAS  PubMed  Google Scholar 

  21. Rosner B (1983) Percentage points for a generalized ESD many-outlier procedure. Technometrics 25:165–172

    Article  Google Scholar 

  22. Wang XS, Tipper S, Appleby PN, Allen NE, Key TJ, Travis RC (2014) First-morning urinary melatonin and breast cancer risk in the Guernsey Study. Am J Epidemiol 179:584–593

    Article  PubMed  PubMed Central  Google Scholar 

  23. Brown SB, Hankinson SE, Eliassen AH et al (2015) Urinary melatonin concentration and the risk of breast cancer in Nurses’ Health Study II. Am J Epidemiol 181:155–162

    Article  PubMed  Google Scholar 

  24. Schernhammer ES, Hankinson SE (2009) Urinary melatonin levels and postmenopausal breast cancer risk in the Nurses’ Health Study cohort. Cancer Epidemiol Biomarkers Prev. 18:74–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cos S, Gonzalez A, Guezmes A et al (2006) Melatonin inhibits the growth of DMBA-induced mammary tumors by decreasing the local biosynthesis of estrogens through the modulation of aromatase activity. Int J Cancer 118:274–278

    Article  CAS  PubMed  Google Scholar 

  26. Bondi CD, Alonso-Gonzalez C, Clafshenkel WP et al (2014) The effect of estradiol, progesterone, and melatonin on estrous cycling and ovarian aromatase expression in intact female mice. Eur J Obstet Gynecol Reprod Biol 174:80–85

    Article  CAS  PubMed  Google Scholar 

  27. del Rio B, Garcia Pedrero JM, Martinez-Campa C, Zuazua P, Lazo PS, Ramos S (2004) Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin. J Biol Chem 279:38294–38302

    Article  PubMed  Google Scholar 

  28. Ciucci A, Zannoni GF, Travaglia D, Petrillo M, Scambia G, Gallo D (2014) Prognostic significance of the estrogen receptor beta (ERbeta) isoforms ERbeta1, ERbeta2, and ERbeta5 in advanced serous ovarian cancer. Gynecol Oncol 132:351–359

    Article  CAS  PubMed  Google Scholar 

  29. Schernhammer ES, Rosner B, Willett WC, Laden F, Colditz GA, Hankinson SE (2004) Epidemiology of urinary melatonin in women and its relation to other hormones and night work. Cancer Epidemiol Biomarkers Prev. 13:936–943

    CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank the participants and staff of the Nurses’ Health Studies for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. This work was supported by National Cancer Institute Grants UM1 CA186107, P01 CA87969, R01 CA49449, UM1 CA176726, and R01 CA67262.

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Correspondence to Elizabeth M. Poole.

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This analysis was approved by the institutional review board of Brigham and Women’s Hospital. Study participants provided informed consent.

Conflict of interest

The authors have no conflicts of interest to disclose.

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Poole, E.M., Schernhammer, E., Mills, L. et al. Urinary melatonin and risk of ovarian cancer. Cancer Causes Control 26, 1501–1506 (2015). https://doi.org/10.1007/s10552-015-0640-2

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  • DOI: https://doi.org/10.1007/s10552-015-0640-2

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