The Role of Antioxidants and Vitamin A in Ovarian Cancer: Results From the Women's Health Initiative

Abstract

Antioxidant nutrients and carotenoids have been inconsistently associated with ovarian cancer risk. We examined the relationship between intake of dietary and supplemental antioxidant nutrients including vitamins C, E, and selenium as well as carotenoids and vitamin A and ovarian cancer in 133,614 postmenopausal women enrolled in the Women's Health Initiative (WHI) study. Dietary intake was assessed using a food frequency questionnaire, and ovarian cancer endpoints were centrally adjudicated. Cox regression models were used to estimate the risk for invasive ovarian cancer in relation to each of the antioxidant nutrients and carotenoids under consideration using models stratified for a WHI study component. A total of 451 cases of invasive ovarian cancer were diagnosed over 8.3 yr of follow-up. Dietary intake at baseline was not significantly different for cases vs. controls. Cases reported greater intake of supplemental vitamin C (358.0 mg/day vs. 291.6 mg/day, respectively; P = 0.024). Multivariate modeling ( P for trend) of the risk for developing ovarian cancer did not suggest any significant relationships among dietary factors and ovarian cancer risk. The results from this prospective study of well-nourished, postmenopausal women suggest that intake of dietary antioxidants, carotenoids, and vitamin A are not associated with a reduction in ovarian cancer risk.

ACKNOWLEDGMENTS

Supported by the National Institutes of Health (NIH) Department of Health and Human Services, National Heart, Lung and Blood Institute, with additional support from NIH GCRC MO1RR0045. Clinical trials listing: NCT 00000611. We would like to acknowledge the study participants as well as the investigators and staff who gave their time to ensure the success of the Women's Health Initiative. Further, we would like to recognize Alicia Sato and Mary Pettinger for their support with the statistical analysis and Alyssa Smith who provides unending support to the publication process. Special acknowledgment to the WHI study team. A full listing of theWHI investigators can be found at http://www.whi.org. A shortlist is provided here. Program Office, National Heart, Lung, and Blood Institute, Bethesda, Maryland: Elizabeth Nabel, Jacques Rossouw, Shari Ludlam, Linda Pottern, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: Fred Hutchinson Cancer Research Center, Seattle, WA: Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L. Kooperberg, Ruth E. Patterson, Anne McTiernan; Wake Forest University School of Medicine, Winston-Salem, NC: Sally Shumaker; Medical Research Labs, Highland Heights, KY: Evan Stein; University of California at San Francisco, San Francisco, CA: Steven Cummings. Clinical Centers: Albert Einstein College of Medicine, Bronx, NY: Sylvia Wassertheil-Smoller; Baylor College of Medicine, Houston, TX: Jennifer Hays; Brigham and Women's Hospital, Harvard Medical School, Boston, MA: JoAnn Manson; Brown University, Providence, RI: Annlouise R. Assaf; Emory University, Atlanta, GA: Lawrence Phillips; Fred Hutchinson Cancer Research Center, Seattle, WA: Shirley Beresford; George Washington University Medical Center, Washington, DC: Judith Hsia; Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA: Rowan Chlebowski; Kaiser Permanente Center for Health Research, Portland, OR: Evelyn Whitlock; Kaiser Permanente Division of Research, Oakland, CA: Bette Caan; Medical College of Wisconsin, Milwaukee, WI: Jane Morley Kotchen; MedStar Research Institute/Howard University, Washington, DC: Barbara V. Howard; Northwestern University, Chicago/Evanston, IL: Linda Van Horn; Rush Medical Center, Chicago, IL: Henry Black; Stanford Prevention Research Center, Stanford, CA: Marcia L. Stefanick; State University of New York at Stony Brook, Stony Brook, NY: Dorothy Lane; The Ohio State University, Columbus, OH: Rebecca Jackson; University of Alabama at Birmingham, Birmingham, AL: Cora E. Lewis; University of Arizona, Tucson/Phoenix, AZ: Tamsen Bassford; University at Buffalo, Buffalo, NY: Jean Wactawski-Wende; University of California at Davis, Sacramento, CA: John Robbins; University of California at Irvine, CA: F. Allan Hubbell; University of California at Los Angeles, Los Angeles, CA: Howard Judd; University of California at San Diego, LaJolla/Chula Vista, CA: Robert D. Langer; University of Cincinnati, Cincinnati, OH: Margery Gass; University of Florida, Gainesville/Jacksonville, FL: Marian Limacher; University of Hawaii, Honolulu, HI: David Curb; University of Iowa, Iowa City/Davenport, IA: Robert Wallace; University of Massachusetts/Fallon Clinic, Worcester, MA: Judith Ockene; University of Medicine and Dentistry of New Jersey, Newark, NJ: Norman Lasser; University of Miami, Miami, FL: Mary Jo O'Sullivan; University of Minnesota, Minneapolis, MN: Karen Margolis; University of Nevada, Reno, NV: Robert Brunner; University of North Carolina, Chapel Hill, NC: Gerardo Heiss; University of Pittsburgh, Pittsburgh, PA: Lewis Kuller; University of Tennessee, Memphis, TN: Karen C. Johnson; University of Texas Health Science Center, San Antonio, TX: Robert Brzyski; University of Wisconsin, Madison, WI: Gloria E. Sarto; Wake Forest University School of Medicine, Winston-Salem, NC: Denise Bonds; Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI: Susan Hendrix.

Notes

∗ P < 0.05;

∗∗ P < 0.01;

∗∗∗ P < 0.001.

^a Abbreviations are as follows: WHI, Women's Health Initiative; RAE, retinol activity equivalents; RE, retinol equivalents.

^b P value < 0.05; Student's t-test difference of means for cases vs. controls.

^c Only β -carotene was reported to be taken as a dietary supplement; all others reported for diet only.

^d Only data for supplemental selenium reported, as accurate dietary exposure estimates are not available.

^a Abbreviations are as follows: CI, confidence interval; RAE, retinol activity equivalents; ATE, α -tocopherol equivalents. Cox models stratified on clinical trial and/or observational study participation adjusted for age, log calories, No. breast/ovary cancer relatives, dietary modification randomization arm, hysterectomy status, minority race, pack-years smoking, physical activity, nonsteroidal anti-inflammatory drug use, parity, infertility, duration of oral contraceptive use, lifetime ovulatory cycles, partial oophorectomy, age at menopause, and HT usage at entry.

^b Only β -carotene was reported to be taken as a dietary supplement; all others reported for diet only.

^c Only data for supplemental selenium reported, as accurate dietary exposure estimates are not available.