Cancer Causes & Control

, Volume 25, Issue 7, pp 795–808 | Cite as

Dairy food and nutrient intake in different life periods in relation to risk of ovarian cancer

  • Melissa A. Merritt
  • Elizabeth M. Poole
  • Susan E. Hankinson
  • Walter C. Willett
  • Shelley S. Tworoger
Original paper



High lactose intake has been suggested to increase epithelial ovarian cancer (EOC) risk. We evaluated the association between lactose consumed during specific life periods (high school, premenopause, and postmenopause) and later risk of EOC.


We assessed the association of dairy food and nutrient intake with risk of EOC during 28 years of follow-up including 764 cases in the Nurses’ Health Study (NHS) and NHSII. Cox proportional hazards regression was used to model the hazard ratios (HRs) and 95 % confidence intervals (CIs) for EOC across categories of dairy food or nutrient intake. We examined dietary intake in adulthood overall, as well as during premenopausal/postmenopausal years and high school.


In analyses of the highest versus lowest cumulative average intake in adulthood, we observed a non-significant inverse association with skim milk intake (HR 0.76, 95 % CI 0.54–1.06, p trend = 0.05), a non-significant inverse association with lactose intake (HR 0.87, 95 % CI 0.69–1.11, p trend = 0.22) and no association with consumption of whole milk, dairy calcium, or dairy fat. Similar risk estimates were observed for dairy food/nutrient intake during high school, premenopause or postmenopause. Lactose intake in adulthood was inversely associated with risk of endometrioid EOC (HR 0.32, 95 % CI 0.16–0.65, p trend < 0.001).


These findings do not support the hypothesis that higher lactose intake increases EOC risk. The inverse association with endometrioid tumors deserves further study.


Ovarian cancer Dairy Milk Lactose Calcium Fat 



The authors thank the participants and staff of the NHS and NHSII cohorts for their dedication to these studies and their contribution to this research. The authors thank 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 research was supported by the National Cancer Institute, National Institutes of Health Grants P01 CA87969 and R01 CA50385 and training Grants to M.A.M. (R25 CA098566) and E.M.P. (T32 CA009001).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2014_381_MOESM1_ESM.docx (35 kb)
Supplementary material 1 (DOCX 34 kb)


  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917PubMedCrossRefGoogle Scholar
  2. 2.
    Cramer DW, Harlow BL, Willett WC, Welch WR, Bell DA, Scully RE, Ng WG, Knapp RC (1989) Galactose consumption and metabolism in relation to the risk of ovarian cancer. Lancet 2(8654):66–71PubMedCrossRefGoogle Scholar
  3. 3.
    Chen YT, Mattison DR, Feigenbaum L, Fukui H, Schulman JD (1981) Reduction in oocyte number following prenatal exposure to a diet high in galactose. Science 214(4525):1145–1147PubMedCrossRefGoogle Scholar
  4. 4.
    Swartz WJ, Mattison DR (1988) Galactose inhibition of ovulation in mice. Fertil Steril 49(3):522–526PubMedGoogle Scholar
  5. 5.
    Genkinger JM, Hunter DJ, Spiegelman D, Anderson KE, Arslan A, Beeson WL, Buring JE, Fraser GE, Freudenheim JL, Goldbohm RA, Hankinson SE, Jacobs DR Jr, Koushik A, Lacey JV Jr, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Rodriguez C, Rohan TE, Schouten LJ, Shore R, Smit E, Wolk A, Zhang SM, Smith-Warner SA (2006) Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomark Prev 15(2):364–372CrossRefGoogle Scholar
  6. 6.
    Larsson SC, Orsini N, Wolk A (2006) Milk, milk products and lactose intake and ovarian cancer risk: a meta-analysis of epidemiological studies. Int J Cancer 118(2):431–441PubMedCrossRefGoogle Scholar
  7. 7.
    Fairfield KM, Hunter DJ, Colditz GA, Fuchs CS, Cramer DW, Speizer FE, Willett WC, Hankinson SE (2004) A prospective study of dietary lactose and ovarian cancer. Int J Cancer 110(2):271–277PubMedCrossRefGoogle Scholar
  8. 8.
    Gates MA, Rosner BA, Hecht JL, Tworoger SS (2010) Risk factors for epithelial ovarian cancer by histologic subtype. Am J Epidemiol 171(1):45–53PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Kurian AW, Balise RR, McGuire V, Whittemore AS (2005) Histologic types of epithelial ovarian cancer: have they different risk factors? Gynecol Oncol 96(2):520–530PubMedCrossRefGoogle Scholar
  10. 10.
    Yang HP, Trabert B, Murphy MA, Sherman ME, Sampson JN, Brinton LA, Hartge P, Hollenbeck A, Park Y, Wentzensen N (2012) Ovarian cancer risk factors by histologic subtypes in the NIH-AARP diet and health study. Int J Cancer 131(4):938–948PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Merritt MA, Cramer DW, Vitonis AF, Titus LJ, Terry KL (2013) Dairy foods and nutrients in relation to risk of ovarian cancer and major histological subtypes. Int J Cancer 132(5):1114–1124PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Lee JE, Willett WC, Fuchs CS, Smith-Warner SA, Wu K, Ma J, Giovannucci E (2011) Folate intake and risk of colorectal cancer and adenoma: modification by time. Am J Clin Nutr 93(4):817–825PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Cho E, Chen WY, Hunter DJ, Stampfer MJ, Colditz GA, Hankinson SE, Willett WC (2006) Red meat intake and risk of breast cancer among premenopausal women. Arch Intern Med 166(20):2253–2259PubMedCrossRefGoogle Scholar
  14. 14.
    Linos E, Willett WC (2007) Diet and breast cancer risk reduction. J Natl Compr Canc Netw 5(8):711–718PubMedGoogle Scholar
  15. 15.
    Linos E, Willett WC, Cho E, Colditz G, Frazier LA (2008) Red meat consumption during adolescence among premenopausal women and risk of breast cancer. Cancer Epidemiol Biomark Prev 17(8):2146–2151CrossRefGoogle Scholar
  16. 16.
    Missmer SA, Smith-Warner SA, Spiegelman D, Yaun SS, Adami HO, Beeson WL, van den Brandt PA, Fraser GE, Freudenheim JL, Goldbohm RA, Graham S, Kushi LH, Miller AB, Potter JD, Rohan TE, Speizer FE, Toniolo P, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hunter DJ (2002) Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies. Int J Epidemiol 31(1):78–85PubMedCrossRefGoogle Scholar
  17. 17.
    Colditz GA, Hankinson SE (2005) The Nurses’ Health Study: lifestyle and health among women. Nat Rev Cancer 5(5):388–396PubMedCrossRefGoogle Scholar
  18. 18.
    Rockhill B, Willett WC, Hunter DJ, Manson JE, Hankinson SE, Spiegelman D, Colditz GA (1998) Physical activity and breast cancer risk in a cohort of young women. J Natl Cancer Inst 90(15):1155–1160PubMedCrossRefGoogle Scholar
  19. 19.
    Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC (1992) Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol 135(10):1114–1126 discussion 1127–1136PubMedGoogle Scholar
  20. 20.
    Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J, Hennekens CH, Speizer FE (1985) Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 122(1):51–65PubMedGoogle Scholar
  21. 21.
    Salvini S, Hunter DJ, Sampson L, Stampfer MJ, Colditz GA, Rosner B, Willett WC (1989) Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol 18(4):858–867PubMedCrossRefGoogle Scholar
  22. 22.
    U.S. Department of Agriculture Agricultural Research Service (2011) USDA National Nutrient Database for Standard Reference Google Scholar
  23. 23.
    Maruti SS, Feskanich D, Colditz GA, Frazier AL, Sampson LA, Michels KB, Hunter DJ, Spiegelman D, Willett WC (2005) Adult recall of adolescent diet: reproducibility and comparison with maternal reporting. Am J Epidemiol 161(1):89–97PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Frazier AL, Willett WC, Colditz GA (1995) Reproducibility of recall of adolescent diet: Nurses’ Health Study (United States). Cancer Causes Control 6(6):499–506PubMedCrossRefGoogle Scholar
  25. 25.
    Tworoger SS, Hecht JL, Giovannucci E, Hankinson SE (2006) Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer. Am J Epidemiol 163(12):1101–1111PubMedCrossRefGoogle Scholar
  26. 26.
    Zhang X, Lee JE, Ma J, Je Y, Wu K, Willett WC, Fuchs CS, Giovannucci EL (2012) Prospective cohort studies of vitamin B-6 intake and colorectal cancer incidence: modification by time? Am J Clin Nutr 96(4):874–881PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124(1):17–27PubMedGoogle Scholar
  28. 28.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188PubMedCrossRefGoogle Scholar
  29. 29.
    Glynn RJ, Rosner B (2004) Methods to evaluate risks for composite end points and their individual components. J Clin Epidemiol 57(2):113–122PubMedCrossRefGoogle Scholar
  30. 30.
    Poole EM, Merritt MA, Jordan SJ, Yang HP, Hankinson SE, Park Y, Rosner B, Webb PM, Cramer DW, Wentzensen N, Terry KL, Tworoger SS (2013) Hormonal and reproductive risk factors for epithelial ovarian cancer by tumor aggressiveness. Cancer Epidemiol Biomark Prev 22(3):429–437CrossRefGoogle Scholar
  31. 31.
    Cramer D, Welch WR (1983) Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. J Natl Cancer Inst 71(4):717–721PubMedGoogle Scholar
  32. 32.
    Koralek DO, Bertone-Johnson ER, Leitzmann MF, Sturgeon SR, Lacey JV Jr, Schairer C, Schatzkin A (2006) Relationship between calcium, lactose, vitamin D, and dairy products and ovarian cancer. Nutr Cancer 56(1):22–30PubMedCrossRefGoogle Scholar
  33. 33.
    Mommers M, Schouten LJ, Goldbohm RA, van den Brandt PA (2006) Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on diet and cancer. Br J Cancer 94(1):165–170PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Kushi LH, Mink PJ, Folsom AR, Anderson KE, Zheng W, Lazovich D, Sellers TA (1999) Prospective study of diet and ovarian cancer. Am J Epidemiol 149(1):21–31PubMedCrossRefGoogle Scholar
  35. 35.
    Larsson SC, Bergkvist L, Wolk A (2004) Milk and lactose intakes and ovarian cancer risk in the Swedish Mammography Cohort. Am J Clin Nutr 80(5):1353–1357PubMedGoogle Scholar
  36. 36.
    Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies. Lancet Oncol 13(4):385–394PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Merritt MA, De Pari M, Vitonis AF, Titus LJ, Cramer DW, Terry KL (2013) Reproductive characteristics in relation to ovarian cancer risk by histologic pathways. Hum Reprod 28(5):1406–1417PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Somigliana E, Vigano P, Parazzini F, Stoppelli S, Giambattista E, Vercellini P (2006) Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol 101(2):331–341PubMedCrossRefGoogle Scholar
  39. 39.
    Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, Yang W, Heravi-Moussavi A, Giuliany R, Chow C, Fee J, Zayed A, Prentice L, Melnyk N, Turashvili G, Delaney AD, Madore J, Yip S, McPherson AW, Ha G, Bell L, Fereday S, Tam A, Galletta L, Tonin PN, Provencher D, Miller D, Jones SJ, Moore RA, Morin GB, Oloumi A, Boyd N, Aparicio SA, Shih IM, Mes-Masson AM, Bowtell DD, Hirst M, Gilks B, Marra MA, Huntsman DG (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 363(16):1532–1543PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA (2013) Dairy-food, calcium, magnesium, and vitamin d intake and endometriosis: a prospective cohort study. Am J Epidemiol 177(5):420–430PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Trabert B, Peters U, De Roos AJ, Scholes D, Holt VL (2011) Diet and risk of endometriosis in a population-based case–control study. Br J Nutr 105(3):459–467PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Parazzini F, Chiaffarino F, Surace M, Chatenoud L, Cipriani S, Chiantera V, Benzi G, Fedele L (2004) Selected food intake and risk of endometriosis. Hum Reprod 19(8):1755–1759PubMedCrossRefGoogle Scholar
  43. 43.
    Zemel MB, Sun X (2008) Dietary calcium and dairy products modulate oxidative and inflammatory stress in mice and humans. J Nutr 138(6):1047–1052PubMedGoogle Scholar
  44. 44.
    Hartmann S, Lacorn M, Steinhart H (1998) Natural occurrence of steroid hormones in food. Food Chem 62(1):7–20CrossRefGoogle Scholar
  45. 45.
    Crosignani P, Olive D, Bergqvist A, Luciano A (2006) Advances in the management of endometriosis: an update for clinicians. Hum Reprod Update 12(2):179–189PubMedCrossRefGoogle Scholar
  46. 46.
    Nagle CM, Bain CJ, Green AC, Webb PM (2008) The influence of reproductive and hormonal factors on ovarian cancer survival. Int J Gynecol Cancer 18(3):407–413PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Melissa A. Merritt
    • 1
    • 2
    • 3
    • 7
  • Elizabeth M. Poole
    • 1
    • 4
  • Susan E. Hankinson
    • 1
    • 4
    • 5
  • Walter C. Willett
    • 1
    • 4
    • 6
  • Shelley S. Tworoger
    • 1
    • 4
  1. 1.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  2. 2.OB/GYN Epidemiology CenterBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of Biostatistics and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  4. 4.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  5. 5.Division of Biostatistics and EpidemiologyUniversity of MassachusettsAmherstUSA
  6. 6.Department of NutritionHarvard School of Public HealthBostonUSA
  7. 7.Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK

Personalised recommendations