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Circulating prolactin levels and risk of epithelial ovarian cancer

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Abstract

Purpose

Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown.

Methods

We conducted a nested case–control study of 230 cases and 432 individually matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer. We also assessed whether lifestyle and reproductive factors are associated with circulating prolactin among controls.

Results

Prolactin levels were significantly lower among post- versus pre-menopausal women, parous versus nulliparous women, and past versus never users of oral contraceptives in our cross-sectional analysis of controls. In our nested case–control study, we observed a non-significant positive association between circulating prolactin and ovarian cancer risk (ORQ4vsQ1 1.56, 95 % CI 0.94, 2.63, p trend 0.15). Our findings were similar in multivariate-adjusted models and in the subgroup of women who donated blood ≥5 years prior to diagnosis. We observed a significant positive association between prolactin and risk for the subgroup of women with BMI ≥25 kg/m2 (ORQ4vsQ1 3.10, 95 % CI 1.39, 6.90), but not for women with BMI <25 kg/m2 (ORQ4vsQ1 0.81, 95 % CI 0.40, 1.64).

Conclusions

Our findings suggest that prolactin may be associated with increased risk of ovarian cancer, particularly in overweight/obese women. Factors associated with reduced risk of ovarian cancer, such as parity and use of oral contraceptives, were associated with lower prolactin levels, which suggests that modulation of prolactin may be a mechanism underlying their association with risk.

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References

  1. Freeman ME et al (2000) Prolactin: structure, function, and regulation of secretion. Physiol Rev 80(4):1523–1631

    PubMed  CAS  Google Scholar 

  2. Egli M, Leeners B, Kruger TH (2010) Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction. Reproduction 140(5):643–654

    Article  PubMed  CAS  Google Scholar 

  3. Shao R et al (2008) Differences in prolactin receptor (PRLR) in mouse and human fallopian tubes: evidence for multiple regulatory mechanisms controlling PRLR isoform expression in mice. Biol Reprod 79(4):748–757

    Article  PubMed  CAS  Google Scholar 

  4. Schwarzler P et al (1997) Prolactin gene expression and prolactin protein in premenopausal and postmenopausal human ovaries. Fertil Steril 68(4):696–701

    Article  PubMed  CAS  Google Scholar 

  5. Tan D et al (2011) Prolactin increases survival and migration of ovarian cancer cells: importance of prolactin receptor type and therapeutic potential of S179D and G129R receptor antagonists. Cancer Lett 310(1):101–108

    Article  PubMed  CAS  Google Scholar 

  6. Levina VV et al (2009) Biological significance of prolactin in gynecologic cancers. Cancer Res 69(12):5226–5233

    Article  PubMed  CAS  Google Scholar 

  7. Osterholzer HO, Streibel EJ, Nicosia SV (1985) Growth effects of protein hormones on cultured rabbit ovarian surface epithelial cells. Biol Reprod 33(1):247–258

    Article  PubMed  CAS  Google Scholar 

  8. Asai-Sato M et al (2005) Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation or cisplatin treatment. Int J Cancer 115(4):539–544

    Article  PubMed  CAS  Google Scholar 

  9. Lennartsson AK, Jonsdottir IH (2011) Prolactin in response to acute psychosocial stress in healthy men and women. Psychoneuroendocrinology 36(10):1530–1539

    Article  PubMed  CAS  Google Scholar 

  10. Lee JW et al (2009) Surgical stress promotes tumor growth in ovarian carcinoma. Clin Cancer Res 15(8):2695–2702

    Article  PubMed  Google Scholar 

  11. Thaker PH et al (2006) Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med 12(8):939–944

    Article  PubMed  CAS  Google Scholar 

  12. Gregoriou G et al (1999) Evaluation of serum prolactin levels in patients with endometriosis and infertility. Gynecol Obstet Invest 48(1):48–51

    Article  PubMed  CAS  Google Scholar 

  13. Eliassen AH, Tworoger SS, Hankinson SE (2007) Reproductive factors and family history of breast cancer in relation to plasma prolactin levels in premenopausal and postmenopausal women. Int J Cancer 120(7):1536–1541

    Article  PubMed  CAS  Google Scholar 

  14. Mor G et al (2005) Serum protein markers for early detection of ovarian cancer. Proc Natl Acad Sci USA 102(21):7677–7682

    Article  PubMed  CAS  Google Scholar 

  15. Lu D et al (2011) Comparison of candidate serologic markers for type I and type II ovarian cancer. Gynecol Oncol 122(3):560–566

    Article  PubMed  CAS  Google Scholar 

  16. Clendenen TV et al (2011) Circulating inflammation markers and risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 20(5):799–810

    Article  PubMed  CAS  Google Scholar 

  17. Rosner B (1983) Percentage points for a generalized ESD many-outlier procedure. Technometrics 25(2):165–172

    Article  Google Scholar 

  18. van Buuren S (2007) Multiple imputation of discrete and continuous data by fully conditional specification. Stat Methods Med Res 16(3):219–242

    Article  PubMed  Google Scholar 

  19. Tanner MJ, Hadlow NC, Wardrop R (2011) Variation of female prolactin levels with menopausal status and phase of menstrual cycle. Aust N Z J Obstet Gynaecol 51(4):321–324

    Article  PubMed  Google Scholar 

  20. Faupel-Badger JM et al (2010) Prolactin serum levels and breast cancer: relationships with risk factors and tumour characteristics among pre- and postmenopausal women in a population-based case-control study from Poland. Br J Cancer 103(7):1097–1102

    Article  PubMed  CAS  Google Scholar 

  21. Reyes FI, Winter JS, Faiman C (1977) Pituitary-ovarian relationships preceding the menopause. I. A cross-sectional study of serum follice-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone levels. Am J Obstet Gynecol 129(5):557–564

    PubMed  CAS  Google Scholar 

  22. Love RR et al (1991) Prolactin and growth hormone levels in premenopausal women with breast cancer and healthy women with a strong family history of breast cancer. Cancer 68(6):1401–1405

    Article  PubMed  CAS  Google Scholar 

  23. Meyer F et al (1986) Endogenous sex hormones, prolactin, and breast cancer in premenopausal women. J Natl Cancer Inst 77(3):613–616

    PubMed  CAS  Google Scholar 

  24. Yu MC et al (1981) Elevated levels of prolactin in nulliparous women. Br J Cancer 43(6):826–831

    Article  PubMed  CAS  Google Scholar 

  25. Bernstein L et al (1985) Estrogen and sex hormone-binding globulin levels in nulliparous and parous women. J Natl Cancer Inst 74(4):741–745

    PubMed  CAS  Google Scholar 

  26. Kwa HG et al (1981) Plasma prolactin levels and breast cancer: relation to parity, weight and height, and age at first birth. Int J Cancer 28(1):31–34

    Article  PubMed  CAS  Google Scholar 

  27. Wang DY et al (1988) The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women. Eur J Cancer Clin Oncol 24(7):1225–1231

    Article  PubMed  CAS  Google Scholar 

  28. Wang DY et al (1984) Nyctohemeral changes in plasma prolactin levels and their relationship to breast cancer risk. Int J Cancer 33(5):629–632

    Article  PubMed  CAS  Google Scholar 

  29. Nagata C et al (2011) Associations of body size and reproductive factors with circulating levels of sex hormones and prolactin in premenopausal Japanese women. Cancer Causes Control 22(4):581–588

    Article  PubMed  Google Scholar 

  30. Musey VC et al (1987) Long-term effect of a first pregnancy on the secretion of prolactin. N Engl J Med 316(5):229–234

    Article  PubMed  CAS  Google Scholar 

  31. Wang DY et al (1987) The relationship between blood prolactin levels and risk of breast cancer in premenopausal women. Eur J Cancer Clin Oncol 23(10):1541–1548

    Article  PubMed  CAS  Google Scholar 

  32. Love RR, Rose DP (1985) Elevated bioactive prolactin in women at risk for familial breast cancer. Eur J Cancer Clin Oncol 21(12):1553–1554

    Article  PubMed  CAS  Google Scholar 

  33. Levin PA, Malarkey WB (1981) Daughters of women with breast cancer have elevated mean 24-hour prolactin (PRL) levels and a partial resistance of PRL to dopamine suppression. J Clin Endocrinol Metab 53(1):179–183

    Article  PubMed  CAS  Google Scholar 

  34. Henderson BR et al (1975) Elevated serum levels of estrogen and prolactin in daughters of patients with breast cancer. N Engl J Med 293(16):790–795

    Article  PubMed  CAS  Google Scholar 

  35. Ingram DM, Nottage EM, Roberts AN (1990) Prolactin and breast cancer risk. Med J Aust 153(8):469–473

    PubMed  CAS  Google Scholar 

  36. Jernstrom HC, Olsson H, Borg A (1997) Reduced testosterone, 17 beta-oestradiol and sexual hormone binding globulin, and increased insulin-like growth factor-1 concentrations, in healthy nulligravid women aged 19–25 years who were first and/or second degree relatives to breast cancer patients. Eur J Cancer Prev 6(4):330–340

    Article  PubMed  CAS  Google Scholar 

  37. de Waard F, Kwa HG, Poortman J (1980) Plasma prolactin levels in women at postmenopausal age with a family history of breast cancer or a prescription for antihypertensive Rauwolfia treatment. Oncology 37(1):33–36

    Article  PubMed  Google Scholar 

  38. Fishman J et al (1978) Plasma hormone profiles of young women at risk for familial breast cancer. Cancer Res 38(11 Pt 2):4006–4011

    PubMed  CAS  Google Scholar 

  39. Hankinson SE et al (1995) Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses’ Health Study (United States). Cancer Causes Control 6(3):217–224

    Article  PubMed  CAS  Google Scholar 

  40. Harvey AE, Lashinger LM, Hursting SD (2011) The growing challenge of obesity and cancer: an inflammatory issue. Ann N Y Acad Sci 1229:45–52

    Article  PubMed  CAS  Google Scholar 

  41. Bouilly J et al (2012) Prolactin signaling mechanisms in ovary. Mol Cell Endocrinol 356(1–2):80–87

    Article  PubMed  CAS  Google Scholar 

  42. Hoffmann T, Penel C, Ronin C (1993) Glycosylation of human prolactin regulates hormone bioactivity and metabolic clearance. J Endocrinol Invest 16(10):807–816

    PubMed  CAS  Google Scholar 

  43. Sinha YN (1995) Structural variants of prolactin: occurrence and physiological significance. Endocr Rev 16(3):354–369

    PubMed  CAS  Google Scholar 

  44. Arslan AA et al (2008) Reproducibility of serum pituitary hormones in women. Cancer Epidemiol Biomarkers Prev 17(8):1880–1883

    Article  PubMed  CAS  Google Scholar 

  45. Katznelson L et al (1998) Prolactin pulsatile characteristics in postmenopausal women. J Clin Endocrinol Metab 83(3):761–764

    Article  PubMed  CAS  Google Scholar 

  46. Tworoger SS et al (2007) Effect of a 12-month randomized clinical trial of exercise on serum prolactin concentrations in postmenopausal women. Cancer Epidemiol Biomarkers Prev 16(5):895–899

    Article  PubMed  CAS  Google Scholar 

  47. Fujimoto VY et al (1990) Variability of serum prolactin and progesterone levels in normal women: the relevance of single hormone measurements in the clinical setting. Obstet Gynecol 76(1):71–78

    PubMed  CAS  Google Scholar 

  48. Missmer SA et al (2006) Reproducibility of plasma steroid hormones, prolactin, and insulin-like growth factor levels among premenopausal women over a 2- to 3-year period. Cancer Epidemiol Biomarkers Prev 15(5):972–978

    Article  PubMed  CAS  Google Scholar 

  49. Muti P et al (1996) Reliability of serum hormones in premenopausal and postmenopausal women over a one-year period. Cancer Epidemiol Biomarkers Prev 5(11):917–922

    PubMed  CAS  Google Scholar 

  50. Koenig KL et al (1993) Reliability of serum prolactin measurements in women. Cancer Epidemiol Biomarkers Prev 2(5):411–414

    PubMed  CAS  Google Scholar 

  51. Hankinson SE et al (1995) Reproducibility of plasma hormone levels in postmenopausal women over a 2–3-year period. Cancer Epidemiol Biomarkers Prev 4(6):649–654

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by research grants from the U.S. National Cancer Institute (R21 CA116585, R01 CA098661, and P30CA016087) and the U.S. National Institute of Environmental Health Sciences Center Grant (P30 ES000260).

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The authors declare that they have no conflict of interest.

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Correspondence to Tess V. Clendenen.

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Clendenen, T.V., Arslan, A.A., Lokshin, A.E. et al. Circulating prolactin levels and risk of epithelial ovarian cancer. Cancer Causes Control 24, 741–748 (2013). https://doi.org/10.1007/s10552-013-0156-6

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  • DOI: https://doi.org/10.1007/s10552-013-0156-6

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