Skip to main content
SpringerLink
Log in

Birth spacing and maternal risk of invasive epithelial ovarian cancer in a Swedish nationwide cohort

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

Abstract

Objective

Pregnancies reduce the risk of ovarian cancer, and among multiparous women, levels of circulating progesterone might be higher during pregnancies with wider birth spacing. We hypothesized that childbirth with wider birth spacing might reduce maternal risk of invasive epithelial ovarian cancer more than births with narrower spacing.

Methods

We conducted a case–control study nested in a nationwide cohort of Swedish women from 1961 to 2001. We selected five individually age-matched controls for each case of invasive epithelial ovarian cancer, and analysis for the effect of birth spacing was performed for 5,341 cases and 29,047 controls. We applied unconditional logistic regression analyses adjusting for age, ages at childbirth, educational level, area of residence, and gender of offspring.

Results

Relative risk of invasive epithelial ovarian cancer associated with each one-year increase in average birth spacing is 1.00 (95% CI = 0.98–1.01) among all women and 0.99 (0.98–1.01) among those born before 1935 and less likely to have used oral contraceptives. Further analyses on the biparous and triparous women did not find a consistent association between birth spacing and the risk of ovarian cancer.

Conclusions

Birth spacing is unlikely to be a major determinant underlying the protective effects of childbirth on ovarian cancer risk.

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. Cramer DW, Hutchison GB, Welch WR, Scully RE, Ryan KJ (1983) Determinants of ovarian cancer risk. I. Reproductive experiences and family history. J Natl Cancer Inst 71:711–716

    PubMed  CAS  Google Scholar 

  2. Negri E, Franceschi S, Tzonou A, Booth M, La Vecchia C, Parazzini F, Beral V, Boyle P, Trichopoulos D (1991) Pooled analysis of 3 European case–control studies: I. Reproductive factors and risk of epithelial ovarian cancer. Int J Cancer 49:50–56. doi:10.1002/ijc.2910490110

    Article  PubMed  CAS  Google Scholar 

  3. Whittemore AS, Harris R, Itnyre J (1992) Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Am J Epidemiol 136:1184–1203

    PubMed  CAS  Google Scholar 

  4. Adami HO, Hsieh CC, Lambe M, Trichopoulos D, Leon D, Persson I, Ekbom A, Janson PO (1994) Parity, age at first childbirth, and risk of ovarian cancer. Lancet 344:1250–1254. doi:10.1016/S0140-6736(94) 90749-8

    Article  PubMed  CAS  Google Scholar 

  5. Risch HA, Marrett LD, Howe GR (1994) Parity, contraception, infertility, and the risk of epithelial ovarian cancer. Am J Epidemiol 140:585–597

    PubMed  CAS  Google Scholar 

  6. Purdie D, Green A, Bain C, Siskind V, Ward B, Hacker N, Quinn M, Wright G, Russell P, Susil B (1995) Reproductive and other factors and risk of epithelial ovarian cancer: an Australian case–control study. Survey of Women’s Health Study Group. Int J Cancer 62:678–684. doi:10.1002/ijc.2910620606

    Article  PubMed  CAS  Google Scholar 

  7. Wittenberg J, Cook LS, Rossing MA, Weiss NS (1999) Reproductive risk factors for mucinous and non-mucinous epithelial ovarian cancer. Epidemiology 10:761–763. doi:10.1097/00001648-199911000-00018

    Article  PubMed  CAS  Google Scholar 

  8. Titus-Ernstoff L, Perez K, Cramer DW, Harlow BL, Baron JA, Greenberg ER (2001) Menstrual and reproductive factors in relation to ovarian cancer risk. Br J Cancer 84:714–721. doi:10.1054/bjoc.2000.1596

    Article  PubMed  CAS  Google Scholar 

  9. Riman T, Dickman PW, Nilsson S, Correia N, Nordlinder H, Magnusson CM, Persson IR (2002) Risk factors for invasive epithelial ovarian cancer: results from a Swedish case–control study. Am J Epidemiol 156:363–373. doi:10.1093/aje/kwf048

    Article  PubMed  Google Scholar 

  10. Tung KH, Goodman MT, Wu AH, McDuffie K, Wilkens LR, Kolonel LN, Nomura AM, Terada KY, Carney ME, Sobin LH (2003) Reproductive factors and epithelial ovarian cancer risk by histologic type: a multiethnic case–control study. Am J Epidemiol 158:629–638. doi:10.1093/aje/kwg177

    Article  PubMed  Google Scholar 

  11. Hankinson SE, Colditz GA, Hunter DJ, Willett WC, Stampfer MJ, Rosner B, Hennekens CH, Speizer FE (1995) A prospective study of reproductive factors and risk of epithelial ovarian cancer. Cancer 76:284–290. doi:10.1002/1097-0142(19950715)76:2≤284::AID-CNCR2820760219≥3.0.CO;2-5

    Article  PubMed  CAS  Google Scholar 

  12. Riman T, Nilsson S, Persson IR (2004) Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies. Acta Obstet Gynecol Scand 83:783–795. doi:10.1111/j.0001-6349.2004.00550.x

    Article  PubMed  Google Scholar 

  13. Risch HA (1998) Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 90:1774–1786. doi:10.1093/jnci/90.23.1774

    Article  PubMed  CAS  Google Scholar 

  14. Bu SZ, Yin DL, Ren XH, Jiang LZ, Wu ZJ, Gao QR, Pei G (1997) Progesterone induces apoptosis and up-regulation of p53 expression in human ovarian carcinoma cell lines. Cancer 79:1944–1950. doi:10.1002/(SICI)1097-0142(19970515)79:10≤1944::AID-CNCR15≥3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  15. Yu S, Lee M, Shin S, Park J (2001) Apoptosis induced by progesterone in human ovarian cancer cell line SNU-840. J Cell Biochem 82:445–451. doi:10.1002/jcb.1171

    Article  PubMed  CAS  Google Scholar 

  16. Syed V, Ho SM (2003) Progesterone-induced apoptosis in immortalized normal and malignant human ovarian surface epithelial cells involves enhanced expression of FasL. Oncogene 22:6883–6890. doi:10.1038/sj.onc.1206828

    Article  PubMed  CAS  Google Scholar 

  17. Maccoby EE, Doering CH, Jacklin CN (1979) Kraemer H (2003) Concentrations of sex hormones in umbilical-cord blood: their relation to sex and birth order of infants. Child Dev 50:632–642

    Article  PubMed  CAS  Google Scholar 

  18. Liu Q, Wuu J, Lambe M, Hsieh SF, Ekbom A, Hsieh CC (2002) Transient increase in breast cancer risk after giving birth: postpartum period with the highest risk (Sweden). Cancer Causes Control 13:299–305. doi:10.1023/A:1015287208222

    Article  PubMed  Google Scholar 

  19. Center for Epidemiology (1998) Cancer incidence in Sweden 1995. Center for Epidemiology, Stockholm

    Google Scholar 

  20. Whiteman DC, Murphy MF, Cook LS, Cramer DW, Hartge P, Marchbanks PA, Nasca PC, Ness RB, Purdie DM, Risch HA (2000) Multiple births and risk of epithelial ovarian cancer. J Natl Cancer Inst 92:1172–1177. doi:10.1093/jnci/92.14.1172

    Article  PubMed  CAS  Google Scholar 

  21. Batra S, Sjoberg NO, Aberg A (1978) Human placental lactogen, estradiol-17beta, and progesterone levels in the third trimester and their respective values for detecting twin pregnancy. Am J Obstet Gynecol 131:69–72

    PubMed  CAS  Google Scholar 

  22. Kelsey JL, Whittemore AS (1994) Epidemiology and primary prevention of cancers of the breast, endometrium, and ovary. A brief overview. Ann Epidemiol 4:89–95

    Article  PubMed  CAS  Google Scholar 

  23. Lukanova A, Kaaks R (2005) Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomarkers Prev 14:98–107

    PubMed  CAS  Google Scholar 

  24. Fathalla MF (1971) Incessant ovulation—a factor in ovarian neoplasia? Lancet 2:163. doi:10.1016/S0140-6736(71)92335-X

    Article  PubMed  CAS  Google Scholar 

  25. Stadel BV (1975) The etiology and prevention of ovarian cancer. Am J Obstet Gynecol 123:772–774

    PubMed  CAS  Google Scholar 

  26. Schildkraut JM, Calingaert B, Marchbanks PA, Moorman PG, Rodriguez GC (2002) Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk. J Natl Cancer Inst 94:32–38

    PubMed  CAS  Google Scholar 

  27. Rodriguez GC, Walmer DK, Cline M, Krigman H, Lessey BA, Whitaker RS, Dodge R, Hughes CL (1998) Effect of progestin on the ovarian epithelium of macaques: cancer prevention through apoptosis? J Soc Gynecol Investig 5:271–276. doi:10.1016/S1071-5576(98) 00017-3

    Article  PubMed  CAS  Google Scholar 

  28. Baik I, Lambe M, Liu Q, Cnattingius S, Mucci LA, Riman T, Ekbom A, Adami H-O, Hsieh CC (2007) Gender of offspring and maternal risk of invasive epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 11:2314–2320. doi:10.1158/1055-9965.EPI-07-0645

    Article  Google Scholar 

  29. Kumle M, Weiderpass E, Braaten T, Adami HO, Lund E (2004) Risk for invasive ovarian cancer and borderline ovarian tumours following use of hormonal contraceptives: the Norwegian-Swedish Women’s Lifestyle and Health Cohort Study. Br J Cancer 90:1386–1391. doi:10.1038/sj.bjc.6601715

    Article  PubMed  CAS  Google Scholar 

  30. Gierach GL, Modugno F, Ness RB (2005) Relations of gestational length and timing and type of incomplete pregnancy to ovarian cancer risk. Am J Epidemiol 161:452–461. doi:10.1093/aje/kwi069

    Article  PubMed  Google Scholar 

  31. Schildkraut JM, Schwingl PJ, Bastos E, Evanoff A, Hughes C (1996) Epithelial ovarian cancer risk among women with polycystic ovary syndrome. Obstet Gynecol 88:554–559. doi:10.1016/0029-7844(96) 00226-8

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the reviewers for helpful comments. This research was supported by grant R01CA95112 from the National Institutes of Health, US Public Health Services.

Author information

Authors and Affiliations

  1. Division of Biostatistics and Epidemiology, Cancer Center, University of Massachusetts Medical School, 364 Plantation Street, LRB# 427, Worcester, MA, USA

    Inkyung Baik, Qin Liu & Chung-Cheng Hsieh

  2. Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, LRB# 427, Worcester, MA, USA

    Inkyung Baik, Qin Liu & Chung-Cheng Hsieh

  3. Korea University Ansan Hospital, College of Medicine, Korea University, Seoul, Republic of Korea

    Inkyung Baik

  4. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Mats Lambe, Sven Cnattingius, Hans-Olov Adami & Chung-Cheng Hsieh

  5. Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Lucy Chie

  6. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Lorelei A. Mucci

  7. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Lorelei A. Mucci, Hans-Olov Adami & Chung-Cheng Hsieh

  8. Center for Clinical Research, Dalarna, Sweden

    Tomas Riman

  9. Department of Obstetrics and Gynecology, Falu Hospital, Falun, Sweden

    Tomas Riman

  10. Program in Clinical Epidemiology, Karolinska Hospital, Stockholm, Sweden

    Anders Ekbom

Authors
  1. Inkyung Baik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mats Lambe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucy Chie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sven Cnattingius
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lorelei A. Mucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tomas Riman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anders Ekbom
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hans-Olov Adami
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chung-Cheng Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chung-Cheng Hsieh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baik, I., Lambe, M., Liu, Q. et al. Birth spacing and maternal risk of invasive epithelial ovarian cancer in a Swedish nationwide cohort. Cancer Causes Control 19, 1131–1137 (2008). https://doi.org/10.1007/s10552-008-9178-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-008-9178-x

Keywords

Search

Navigation