Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Abstract
Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate ≥ 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of ≥60 g/day had a HR of 0.93 (95% CI 0.77–1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.
Keywords
Breast cancer CYP3A4 metabolism Grapefruit intake Prospective studiesNotes
Acknowledgments
We thank the participants in the EPIC study and Genevieve Deharveng and Jerome Vignat at IARC for their expertise in data handling.
Funding
The EPIC is funded by: Cancer Research UK; European Commission: Public Health and Consumer Protection Directorate 1993–2004; Research Directorate-General 2005; German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; ISCIII Red de Centros RCESP C03/09, Spain; Spanish Regional Governments of Andalusia, Asturia, Basque country, Murcia, and Navarra; Medical Research Council, UK; the Stroke Association, UK; British Heart Foundation; Department of Health, UK; Food Standards Agency, UK; the Wellcome Trust, UK; Greek Ministry of Health; Greek Ministry of Education; Italian Association for Research on Cancer (AIRC); Dutch Ministry of Public Health, Welfare and Sports; Dutch Ministry of Health; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland). The researchers act independently of the funders.
References
- 1.Bailey DG, Spence JD, Edgar B, Bayliff CD, Arnold JM (1989) Ethanol enhances the hemodynamic effects of felodipine. Clin Invest Med 12:357–362PubMedGoogle Scholar
- 2.Bailey DG, Spence JD, Munoz C, Arnold JM (1991) Interaction of citrus juices with felodipine and nifedipine. Lancet 337:268–269. doi: 10.1016/0140-6736(91)90872-M PubMedCrossRefGoogle Scholar
- 3.Bailey DG, Dresser GK (2004) Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs 4(5):281–297. doi: 10.2165/00129784-200404050-00002 PubMedCrossRefGoogle Scholar
- 4.Guengerich FP (1999) Cytochrome P4503A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol 39:1–17. doi: 10.1146/annurev.pharmtox.39.1.1 PubMedCrossRefGoogle Scholar
- 5.Medical Letter (2005) Drug interactions with grapefruit juice. Obstet Gynecol 105:429–431Google Scholar
- 6.Monroe KR, Murphy SP, Kolonel LN, Pike MC (2007) Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study. Br J Cancer 97(3):440–445PubMedCrossRefGoogle Scholar
- 7.Monroe KR, Murphy SP, Henderson BE et al (2007) Dietary fiber intake and endogenous serum hormone levels in naturally postmenopausal Mexican American women: the Multiethnic Cohort Study. Nutr Cancer 58(2):127–135PubMedGoogle Scholar
- 8.Kim EH, Hankinson SE, Eliassen AH, Willett WC (2008) A prospective study of grapefruit and grapefruit juice intake and breast cancer risk. Br J Cancer 98(1):240–241. doi: 10.1038/sj.bjc.6604105 PubMedCrossRefGoogle Scholar
- 9.Riboli E, Hunt KJ, Slimani N et al (2002) European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 5(6B):1113–1124. doi: 10.1079/PHN2002394 PubMedCrossRefGoogle Scholar
- 10.Kaaks R, Rinaldi S, Key TJ et al (2005) Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12(4):1071–1082. doi: 10.1677/erc.1.01038 PubMedCrossRefGoogle Scholar
- 11.Kaaks R, Berrino F, Key T et al (2005) Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 97(10):755–765PubMedCrossRefGoogle Scholar
- 12.Allen NE, Key TJ, Dossus L et al (2008) Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer 15(2):485–497. doi: 10.1677/ERC-07-0064 PubMedCrossRefGoogle Scholar
- 13.Rinaldi S, Dossus L, Lukanova A et al (2007) Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Epidemiol Biomarkers Prev 16(1):23–29. doi: 10.1158/1055-9965.EPI-06-0755 PubMedCrossRefGoogle Scholar
- 14.Chajès V, Thiébaut AC, Rotival M et al (2008) Association between serum trans-monounsaturated fatty acids and breast cancer risk in the E3 N-EPIC Study. Am J Epidemiol 167(11):1312–1320. doi: 10.1093/aje/kwn069 PubMedCrossRefGoogle Scholar