Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies

Anita Koushik, Molin Wang, Kristin E. Anderson, Piet van den Brandt, Tess V. Clendenen, A. Heather Eliassen, Jo L. Freudenheim, Jeanine M. Genkinger, Niclas Håkansson, James R. Marshall, Marjorie L. McCullough, Anthony B. Miller, Kim Robien, Thomas E. Rohan, Catherine Schairer, Leo J. Schouten, Shelley S. Tworoger, Ying Wang, Alicja Wolk, Anne Zeleniuch-JacquotteStephanie A. Smith-Warner

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Purpose: Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer. Methods: The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Results: Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7–16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95 % confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97–1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99–1.04) for vitamin C (400 mg/day), 1.02 (0.97–1.06) for vitamin E (130 mg/day), and 1.01 (0.96–1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95 % CI 0.89–1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types. Conclusion: These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.

Original languageEnglish (US)
Pages (from-to)1315-1327
Number of pages13
JournalCancer Causes and Control
Issue number9
StatePublished - Sep 2 2015

Bibliographical note

Funding Information:
We would like to thank the participants and staff of each of the cohorts for their valuable contributions and the organizations that funded the infrastructure for each cohort study. The centralization, checking, harmonization, and statistical analyses of the participant-level data from each of the cohorts were funded by Grant P01 CA55075 from the US National Cancer Institute and Grant 20010 from the Fonds de recherche du Québec—Santé. Dr. Anita Koushik currently holds a New Investigator Award from the Canadian Institutes of Health Research.

Publisher Copyright:
© 2015, Springer International Publishing Switzerland.


  • Cohort studies
  • Folate
  • Ovarian cancer
  • Pooled analysis
  • Vitamin A
  • Vitamin C
  • Vitamin E


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