A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer

Flavonoids are antioxidant compounds found in plants, including fruits, vegetables and tea. No prior prospective studies have examined the association between intake of flavonoids in the flavonol and flavone subclasses and ovarian cancer risk. We analyzed the association between intake of 5 common dietary flavonoids and incidence of epithelial ovarian cancer among 66,940 women in the Nurses' Health Study. We calculated each participant's intake of myricetin, kaempferol, quercetin, luteolin and apigenin from dietary data collected at multiple time points, and used Cox proportional hazards regression to model the incidence rate ratio (RR) of ovarian cancer for each quintile of intake. Our analysis included 347 cases diagnosed between 1984 and 2002, and 950,347 person‐years of follow‐up. There was no clear association between total intake of the 5 flavonoids examined and incidence of ovarian cancer (RR = 0.75 for the highest versus lowest quintile, 95% confidence interval [CI] = 0.51–1.09). However, there was a significant 40% decrease in ovarian cancer incidence for the highest versus lowest quintile of kaempferol intake (RR = 0.60, 95% CI = 0.42–0.87; p‐trend = 0.002), and a significant 34% decrease in incidence for the highest versus lowest quintile of luteolin intake (RR = 0.66, 95% CI = 0.49–0.91; p‐trend = 0.01). There was evidence of an inverse association with consumption of tea (nonherbal) and broccoli, the primary contributors to kaempferol intake in our population. These data suggest that dietary intake of certain flavonoids may reduce ovarian cancer risk, although additional prospective studies are needed to further evaluate this association. If confirmed, these results would provide an important target for ovarian cancer prevention. © 2007 Wiley‐Liss, Inc.

[1]  D. Stram,et al.  Diet and risk of ovarian cancer in the California Teachers Study cohort. , 2007, American journal of epidemiology.

[2]  A. Trentham-Dietz,et al.  Alcohol consumption and ovarian cancer risk in a population‐based case–control study , 2006, International journal of cancer.

[3]  C. la Vecchia,et al.  Onion and garlic use and human cancer. , 2006, The American journal of clinical nutrition.

[4]  Xianglin Shi,et al.  Apigenin inhibits tumor angiogenesis through decreasing HIF-1alpha and VEGF expression. , 2006, Carcinogenesis.

[5]  J. Lovegrove,et al.  Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study. , 2006, The British journal of nutrition.

[6]  Xianglin Shi,et al.  Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells. , 2006, The Journal of nutrition.

[7]  K. Moysich,et al.  Consumption of black tea or coffee and risk of ovarian cancer , 2006, International Journal of Gynecologic Cancer.

[8]  Y. Moon,et al.  Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. , 2006, Toxicology in vitro : an international journal published in association with BIBRA.

[9]  G. Ursin,et al.  Dietary Risk Factors for Ovarian Cancer: The Adventist Health Study (United States) , 2006, Cancer Causes & Control.

[10]  R. Goldbohm,et al.  Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies , 2006, British Journal of Cancer.

[11]  R. Goldbohm,et al.  Dairy Products and Ovarian Cancer: A Pooled Analysis of 12 Cohort Studies , 2006, Cancer Epidemiology Biomarkers & Prevention.

[12]  C. la Vecchia,et al.  Pizza consumption and the risk of breast, ovarian and prostate cancer , 2006, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[13]  S. Larsson,et al.  Tea consumption and ovarian cancer risk in a population-based cohort. , 2005, Archives of internal medicine.

[14]  I. Gram,et al.  Fruit and Vegetable Consumption and Risk of Epithelial Ovarian Cancer: The European Prospective Investigation into Cancer and Nutrition , 2005, Cancer Epidemiology Biomarkers & Prevention.

[15]  R. Goldbohm,et al.  Consumption of vegetables and fruits and risk of ovarian carcinoma , 2005, Cancer.

[16]  W. Willett,et al.  Fruits and Vegetables and Ovarian Cancer Risk in a Pooled Analysis of 12 Cohort Studies , 2005, Cancer Epidemiology Biomarkers & Prevention.

[17]  Bing-Hua Jiang,et al.  Apigenin inhibits VEGF and HIF‐1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  A. Whittemore,et al.  Histologic types of epithelial ovarian cancer: have they different risk factors? , 2005, Gynecologic oncology.

[19]  R. Kaaks,et al.  Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. , 2005, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[20]  Jean Marx,et al.  Inflammation and Cancer: The Link Grows Stronger , 2004, Science.

[21]  Christopher J. Rhodes,et al.  Role of oxygen radicals in DNA damage and cancer incidence , 2004, Molecular and Cellular Biochemistry.

[22]  Heiner Boeing,et al.  Dietary Determinants of Epithelial Ovarian Cancer: A Review of the Epidemiologic Literature , 2004, Nutrition and cancer.

[23]  D. Kitts,et al.  Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells , 2004, Molecular and Cellular Biochemistry.

[24]  S. Wen,et al.  A case-control study of diet and the risk of ovarian cancer. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[25]  Insu P. Lee,et al.  Anticancer effects of (-)-epigallocatechin-3-gallate on ovarian carcinoma cell lines. , 2004, Gynecologic oncology.

[26]  Andy H. Lee,et al.  Soy and Isoflavone Intake Are Associated With Reduced Risk of Ovarian Cancer in Southeast China , 2004, Nutrition and cancer.

[27]  D. Purdie,et al.  Coffee, Tea and Caffeine and Risk of Epithelial Ovarian Cancer , 2004, Cancer Causes and Control.

[28]  C. Bain,et al.  Alcohol, wine, and risk of epithelial ovarian cancer. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[29]  Douglas D. Taylor,et al.  Inhibitory effect of genistein and daidzein on ovarian cancer cell growth. , 2004, Anticancer research.

[30]  R. Ness,et al.  Alcohol Consumption and the Risk of Mucinous and Nonmucinous Epithelial Ovarian Cancer , 2003, Obstetrics and gynecology.

[31]  Hongwei Wang,et al.  Flavonoids: Promising anticancer agents , 2003, Medicinal research reviews.

[32]  M. Goodman,et al.  Alcohol Consumption and the Risk of Borderline and Invasive Ovarian Cancer , 2003, Obstetrics and gynecology.

[33]  J. Freudenheim,et al.  Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups. , 2003, The Journal of nutrition.

[34]  M. López-Lázaro Flavonoids as anticancer agents: structure-activity relationship study. , 2002, Current medicinal chemistry. Anti-cancer agents.

[35]  E. Rimm,et al.  Flavonol and flavone intakes in US health professionals. , 2002, Journal of the American Dietetic Association.

[36]  Andy H. Lee,et al.  Tea consumption and ovarian cancer risk: a case-control study in China. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[37]  D. Birt,et al.  Dietary agents in cancer prevention: flavonoids and isoflavonoids. , 2001, Pharmacology & therapeutics.

[38]  R. Meli,et al.  Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A.1. , 2001, Life sciences.

[39]  C. la Vecchia,et al.  Coffee and Alcohol Intake and Risk of Ovarian Cancer: An Italian Case-Control Study , 2001, Nutrition and cancer.

[40]  D. Cramer,et al.  Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer , 2000, International journal of cancer.

[41]  R. Ness,et al.  Possible role of ovarian epithelial inflammation in ovarian cancer. , 1999, Journal of the National Cancer Institute.

[42]  T. J. Doyle,et al.  Tea consumption and cancer incidence in a prospective cohort study of postmenopausal women. , 1996, American journal of epidemiology.

[43]  M. Stampfer,et al.  Test of the National Death Index and Equifax Nationwide Death Search. , 1994, American journal of epidemiology.

[44]  Peter C. H. Hollman,et al.  Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands , 1992 .

[45]  C. la Vecchia,et al.  Alcohol and epithelial ovarian cancer. , 1992, Journal of clinical epidemiology.

[46]  L. Larocca,et al.  Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. , 1990, British Journal of Cancer.

[47]  G A Colditz,et al.  Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. , 1989, International journal of epidemiology.

[48]  S. Shapiro,et al.  Epithelial ovarian cancer and coffee drinking. , 1987, International journal of epidemiology.

[49]  Meir J. Stampfer,et al.  Total energy intake: implications for epidemiologic analyses. , 1986, American journal of epidemiology.

[50]  W. Willett,et al.  Reproducibility and validity of a semiquantitative food frequency questionnaire. , 1985, American journal of epidemiology.

[51]  W. Willett,et al.  Test of the National Death Index. , 1984, American journal of epidemiology.

[52]  Gary Williamson,et al.  Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. , 2005, The American journal of clinical nutrition.

[53]  R. Goldbohm,et al.  Alcohol and ovarian cancer risk: results from the Netherlands Cohort Study , 2004, Cancer Causes & Control.

[54]  J. Marx Cancer research. Inflammation and cancer: the link grows stronger. , 2004, Science.

[55]  G. Beecher Proceedings of the Third International Scientific Symposium on Tea and Human Health: Role of Flavonoids in the Diet , 2003 .

[56]  J. Ross,et al.  Dietary flavonoids: bioavailability, metabolic effects, and safety. , 2002, Annual review of nutrition.

[57]  N. O'Brien,et al.  Dietary flavonols: chemistry, food content, and metabolism. , 2002, Nutrition.

[58]  L. Le Marchand Cancer preventive effects of flavonoids--a review. , 2002, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[59]  C. la Vecchia,et al.  Tea consumption and cancer risk. , 1992, Nutrition and cancer.

[60]  W. Willett,et al.  The use of a self-administered questionnaire to assess diet four years in the past. , 1988, American journal of epidemiology.