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      Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study

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          Abstract

          The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency questionnaire were used to collect general information and dietary intake information. Conditional logistic regression showed a significantly inverse association between total choline and betaine intakes and PLC risk. The multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for PLC for the top ( vs. bottom) tertile were 0.34 (0.24–0.49; P -trend  < 0.001) for total choline and 0.67 (0.48–0.93; P -trend  = 0.011) for betaine. No significant association was observed between the intake of methionine and PLC risk ( P > 0.05). For individual choline compounds, higher consumptions of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin were associated with a lower PLC risk (all P-trend < 0.05). The studied associations were not significantly modified by the folate intake ( P-interactions: 0.488–0.890). Our findings suggest that higher choline and betaine intakes may be associated with a lower risk of PLC.

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          Most cited references39

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          Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study

          Background & Aims Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. The global HCC BRIDGE study was a multiregional, large-scale, longitudinal cohort study undertaken to improve understanding of real-life management of patients with HCC, from diagnosis to death. Methods Data were collected retrospectively from January 2005 to September 2012 by chart reviews of eligible patients newly diagnosed with HCC at participating institutions. Results Forty-two sites in 14 countries contributed final data for 18 031 patients. Asia accounted for 67% of patients, Europe for 20% and North America for 13%. As expected, the most common risk factor was hepatitis C virus in North America, Europe and Japan, and hepatitis B virus in China, South Korea and Taiwan. The most common Barcelona Clinic Liver Cancer stage at diagnosis was C in North America, Europe, China and South Korea, and A in Taiwan and Japan. Across all stages, first HCC treatment was most frequently transarterial chemoembolization in North America, Europe, China and South Korea, percutaneous ethanol injection or radiofrequency ablation in Japan and resection in Taiwan. Survival from first HCC treatment varied significantly by region, with median overall survival not reached for Taiwan and 60, 33, 31, 24 and 23 months for Japan, North America, South Korea, Europe and China respectively (P < 0.0001). Conclusions Initial results from the BRIDGE study confirm previously reported regional trends in patient demographic characteristics and HCC risk factors, document the heterogeneity of treatment approaches across regions/countries and underscore the need for earlier HCC diagnosis worldwide.
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            Concentrations of choline-containing compounds and betaine in common foods.

            Choline is important for normal membrane function, acetylcholine synthesis and methyl group metabolism; the choline requirement for humans is 550 mg/d for men (Adequate Intake). Betaine, a choline derivative, is important because of its role in the donation of methyl groups to homocysteine to form methionine. In tissues and foods, there are multiple choline compounds that contribute to total choline concentration (choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin). In this study, we collected representative food samples and analyzed the choline concentration of 145 common foods using liquid chromatography-mass spectrometry. Foods with the highest total choline concentration (mg/100 g) were: beef liver (418), chicken liver (290), eggs (251), wheat germ (152), bacon (125), dried soybeans (116) and pork (103). The foods with the highest betaine concentration (mg/100 g) were: wheat bran (1339), wheat germ (1241), spinach (645), pretzels (237), shrimp (218) and wheat bread (201). A number of epidemiologic studies have examined the relationship between dietary folic acid and cancer or heart disease. It may be helpful to also consider choline intake as a confounding factor because folate and choline methyl donation can be interchangeable.
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              Choline: critical role during fetal development and dietary requirements in adults.

              S Zeisel (2005)
              Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.
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                Author and article information

                Contributors
                zhuhl@mail.sysu.edu.cn
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                6 April 2017
                6 April 2017
                2017
                : 7
                : 679
                Affiliations
                [1 ]GRID grid.12981.33, School of Public Health, , Sun Yat-sen University, ; Guangzhou, 510080 P.R. China
                [2 ]GRID grid.12981.33, Department of Hepatobiliary Surgery, , Sun Yat-sen University Cancer Center, ; Guangzhou, 510080 P.R. China
                Author information
                http://orcid.org/0000-0003-1658-5528
                Article
                773
                10.1038/s41598-017-00773-w
                5429604
                28386093
                656cc58e-4cfa-4351-992e-8a1abfb5d9fc
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                : 10 June 2016
                : 14 March 2017
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