Serum betaine but not choline is inversely associated with breast cancer risk: a case–control study in China
Choline and betaine are important for DNA methylation and synthesis, and may affect tumor carcinogenesis. To our knowledge, no previous study has examined the association between serum choline and betaine and breast cancer risk. This study aimed to examine whether serum choline and betaine were inversely associated with breast cancer risk among Chinese women.
This hospital-based case–control study consecutively recruited 510 breast cancer cases and 518 frequency-matched (age and residence) controls, and blood samples were available for 500 cases and 500 controls. Serum choline and betaine were assayed by high-performance liquid chromatography–tandem mass spectrometry. Multiple unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs).
An inverse association with breast cancer risk was observed for serum betaine (fourth vs first quartile adjusted OR 0.68, 95 % CI 0.47–0.97) and for the ratio of serum betaine to choline (fourth vs first quartile adjusted OR 0.70, 95 % CI 0.48–1.00), but not for serum choline (fourth vs first quartile adjusted OR 0.80, 95 % CI 0.56–1.15). Serum betaine was inversely associated with breast cancer risk in subjects with below-median dietary folate intake (fourth vs first quartile adjusted OR 0.48, 95 % CI 0.30–0.77).
This study suggested that serum betaine but not choline was inversely associated with breast cancer risk. This result needed to be further confirmed by the prospective studies.
KeywordsSerum choline Serum betaine Breast cancer risk Case–control study
This study was supported by Science and Technology Program of Guangzhou, China (no. 201510010151), and the National Natural Science Foundation of China (no. 81102188). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We gratefully acknowledge the cooperation of the study participants.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
- 4.da Costa KA, Niculescu MD, Craciunescu CN, Fischer LM, Zeisel SH (2006) Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am J Clin Nutr 84:88–94Google Scholar
- 9.Lin J, Lee IM, Cook NR, Selhub J, Manson JE, Buring JE, Zhang SM (2008) Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr 87:734–743Google Scholar
- 10.Wu K, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR, Selhub J (1999) A prospective study on folate, B12, and pyridoxal 5′-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev 8:209–217Google Scholar
- 11.Bae S, Ulrich CM, Neuhouser ML, Malysheva O, Bailey LB, Xiao L, Brown EC, Cushing-Haugen KL, Zheng Y, Cheng TY, Miller JW, Green R, Lane DS, Beresford SA, Caudill MA (2014) Plasma choline metabolites and colorectal cancer risk in the Women’s Health Initiative Observational Study. Cancer Res 74:7442–7452CrossRefGoogle Scholar
- 14.de Vogel S, Ulvik A, Meyer K, Ueland PM, Nygard O, Vollset SE, Tell GS, Gregory JF 3rd, Tretli S, Bjorge T (2014) Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—a large nested case–control study within the JANUS cohort in Norway. Int J Cancer 134:197–206CrossRefGoogle Scholar
- 15.Johansson M, Van Guelpen B, Vollset SE, Hultdin J, Bergh A, Key T, Midttun O, Hallmans G, Ueland PM, Stattin P (2009) One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites. Cancer Epidemiol Biomarkers Prev 18:1538–1543CrossRefGoogle Scholar
- 19.Zhang CX, Ho SC (2009) Validity and reproducibility of a food frequency Questionnaire among Chinese women in Guangdong province. Asia Pac J Clin Nutr 18:240–250Google Scholar
- 20.Yang Y, Wang G, Pan X (2004) China food composition table. Peking University Medical Press, BeijingGoogle Scholar
- 25.Schwahn BC, Chen Z, Laryea MD, Wendel U, Lussier-Cacan S, Genest J Jr, Mar MH, Zeisel SH, Castro C, Garrow T, Rozen R (2003) Homocysteine–betaine interactions in a murine model of 5,10-methylenetetrahydrofolate reductase deficiency. FASEB J 17:512–514Google Scholar
- 33.Katz-Brull R, Seger D, Rivenson-Segal D, Rushkin E, Degani H (2002) Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline–ether–phospholipid synthesis. Cancer Res 62:1966–1970Google Scholar
- 37.Savendahl L, Mar MH, Underwood LE, Zeisel SH (1997) Prolonged fasting in humans results in diminished plasma choline concentrations but does not cause liver dysfunction. Am J Clin Nutr 66:622–625Google Scholar