Choline and betaine intake and risk of breast cancer among post-menopausal women
E Cho, M D Holmes, S E Hankinson, W C Willett, E Cho, M D Holmes, S E Hankinson, W C Willett
Abstract
Background: Choline and betaine, similar to folate, are nutrients involved in one-carbon metabolism and hypothesised to reduce breast cancer risk. No prospective study among post-menopausal women has examined choline and betaine intakes in relation to breast cancer risk.
Methods: We examined the intake of choline and betaine and breast cancer risk among 74 584 post-menopausal women in the Nurses' Health Study. Nutrient intake was assessed using a validated food-frequency questionnaire six times since 1984. During 20 years of follow-up from 1984 until 2004, we documented 3990 incident cases of invasive breast cancer.
Results: Overall, choline (mean+/-s.d.; 326+/-61 mg per day) and betaine (104+/-33 mg per day) intake was not associated with a reduced risk of post-menopausal breast cancer. Participants in the highest quintile of intakes had multivariate relative risks of 1.10 (95% confidence interval (95% CI): 0.99-1.22; P-value, test for trend=0.14) for choline and 0.98 (95% CI: 0.89-1.09; P-value, test for trend=0.96) for betaine, compared with those in the lowest quintiles of intakes. The results were similar in breast cancer stratified by hormone receptor (oestrogen receptor/progesterone receptor) status. The association between choline intake and breast cancer risk did not differ appreciably by alcohol intake (non-drinker, <15 or 15+ g per day) or several other breast cancer risk factors, including family history of breast cancer, history of benign breast disease, body mass index, post-menopausal hormone use, and folate intake.
Conclusion: We found no evidence that higher intakes of choline and betaine reduce risk of breast cancer among post-menopausal women.
References
- Alberg AJ, Selhub J, Shah KV, Viscidi RP, Comstock GW, Helzlsouer KJ (2000) The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine. Cancer Epidemiol Biomarkers Prev 9: 761–764
- Chandar N, Lombardi B (1988) Liver cell proliferation and incidence of hepatocellular carcinomas in rats fed consecutively a choline-devoid and a choline-supplemented diet. Carcinogenesis 9: 259–263
- Chandar N, Lombardi B, Locker J (1989) c-myc gene amplification during hepatocarcinogenesis by a choline-devoid diet. Proc Natl Acad Sci USA 86: 2703–2707
- Chiuve SE, Giovannucci EL, Hankinson SE, Zeisel SH, Dougherty LW, Willett WC, Rimm EB (2007) The association between betaine and choline intakes and the plasma concentrations of homocysteine in women. Am J Clin Nutr 86: 1073–1081
- Cho E, Holmes M, Hankinson SE, Willett WC (2007a) Nutrients involved in one-carbon metabolism and risk of breast cancer among premenopausal women. Cancer Epidemiol Biomarkers Prev 16: 2787–2790
- Cho E, Willett WC, Colditz GA, Fuchs CS, Wu K, Chan AT, Zeisel SH, Giovannucci EL (2007b) Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst 99: 1224–1231
- Cho E, Zeisel SH, Jacques P, Selhub J, Dougherty L, Colditz GA, Willett WC (2006) Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr 83: 905–911
- Colditz GA, Hankinson SE (2005) The Nurses’ Health Study: lifestyle and health among women. Nat Rev Cancer 5: 388–396
- Ericson U, Sonestedt E, Gullberg B, Olsson H, Wirfalt E (2007) High folate intake is associated with lower breast cancer incidence in postmenopausal women in the Malmo Diet and Cancer cohort. Am J Clin Nutr 86: 434–443
- Giovannucci E, Stampfer MJ, Colditz GA, Rimm EB, Trichopoulos D, Rosner BA, Speizer FE, Willett WC (1993) Folate, methionine, and alcohol intake and risk of colorectal adenoma. J Natl Cancer Inst 85: 875–884
- Henning SM, Swendseid ME (1996) The role of folate, choline, and methionine in carcinogenesis induced by methyl-deficient diets. Adv Exp Med Biol 399: 143–155
- Hu FB, Stampfer MJ, Rimm EB, Ascherio A, Rosner BA, Spiegelman D, Willett WC (1999) Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements. Am J Epidemiol 149: 531–540
- Larsson SC, Bergkvist L, Wolk A (2008) Folate intake and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort. Cancer Epidemiol Biomarkers Prev 17: 3444–3449
- Larsson SC, Giovannucci E, Wolk A (2007) Folate and risk of breast cancer: a meta-analysis. J Natl Cancer Inst 99: 64–76
- Lewis SJ, Harbord RM, Harris R, Smith GD (2006) Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J Natl Cancer Inst 98: 1607–1622
- Martinez ME, Henning SM, Alberts DS (2004) Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence. Am J Clin Nutr 79: 691–697
- Maruti SS, Ulrich CM, White E (2008) Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk. Am J Clin Nutr 89: 624–633
- Mason JB (2003) Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J Nutr 133(Suppl 3): 941S–947S
- Mori N, Delsite R, Natarajan K, Kulawiec M, Bhujwalla ZM, Singh KK (2004) Loss of p53 function in colon cancer cells results in increased phosphocholine and total choline. Mol Imaging 3: 319–323
- Ramirez de Molina A, Gutierrez R, Ramos MA, Silva JM, Silva J, Bonilla F, Sanchez JJ, Lacal JC (2002) Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy. Oncogene 21: 4317–4322
- Rohan TE, Jain MG, Howe GR, Miller AB (2000) Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 92: 266–269
- Stampfer MJ, Willett WC, Speizer FE, Dysert DC, Lipnick R, Rosner B, Hennekens CH (1984) Test of the National Death Index. Am J Epidemiol 119: 837–839
- Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, Taylor PR, Virtamo J, Albanes D (2001) Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol 153: 680–687
- US Department of Agriculture (2004) USDA Database for the Choline Content of Common Foods. US Department of Agriculture: Washington, DC, USA
- Villa AM, Caporizzo E, Papagni A, Miozzo L, Del Buttero P, Grilli MD, Amboldi N, Fazio F, Doglia SM, Giglioni B (2005) Choline and phosphatidylcholine fluorescent derivatives localization in carcinoma cells studied by laser scanning confocal fluorescence microscopy. Eur J Cancer 41: 1453–1459
- Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses: review. Am J Epidemiol 124: 17–27
- Xu X, Gammon MD, Zeisel SH, Lee YL, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J (2008) Choline metabolism and risk of breast cancer in a population-based study. FASEB J 22: 2045–2052
- Yates AA, Schlicker SA, Suitor CW (1998) Dietary Reference Intakes: the new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 98: 699–706
- Zeisel SH, Mar M-H, Howe JM, Holden JM (2003a) Erratum: Concentrations of choine-containing compounds and betaine in common foods. J Nutr 133: 1302–1307. J Nutr 133: 2918–2919
- Zeisel SH, Mar MH, Howe JC, Holden JM (2003b) Concentrations of choline-containing compounds and betaine in common foods. J Nutr 133: 1302–1307
- Zhang S, Hunter DJ, Hankinson SE, Giovannucci EL, Rosner BA, Colditz GA, Speizer FE, Willett WC (1999) A prospective study of folate intake and the risk of breast cancer. JAMA 281: 1632–1637
- Zhang SM, Hankinson SE, Hunter DJ, Giovannucci EL, Colditz GA, Willett WC (2005) Folate intake and risk of breast cancer characterized by hormone receptor status. Cancer Epidemiol Biomarkers Prev 14: 2004–2008
Source: PubMed