Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
BACKGROUND
Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low.


METHODS
We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations.


RESULTS
Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk.


CONCLUSIONS
Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.
Departments of Global Public Health and Primary Care.
M
M
Nitter
Departments of Global Public Health and Primary Care.
B
B
Norgård
Departments of Global Public Health and Primary Care stefan.vogel@isf.uib.no.
S
S
de Vogel
Departments of Global Public Health and Primary Care Clinical Science, Section for Pharmacology, University of Bergen, Bergen, Norway Department of Epidemiology, School for Public Health and Primary Care, CAPHRI, Maastricht University, Maastricht, The Netherlands.
S J P M
SJ
Eussen
BEVITAL AS, Bergen.
K
K
Meyer
BEVITAL AS, Bergen.
A
A
Ulvik
Clinical Science, Section for Pharmacology, University of Bergen, Bergen, Norway Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen.
P M
PM
Ueland
Departments of Clinical Science, Section of Cardiology, University of Bergen, Bergen Heart Disease, Haukeland University Hospital, Bergen.
O
O
Nygård
Departments of Global Public Health and Primary Care Norwegian Institute of Public Health, Bergen, Norway.
S E
SE
Vollset
Departments of Global Public Health and Primary Care Norwegian Institute of Public Health, Bergen, Norway.
T
T
Bjørge
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
A
A
Tjønneland
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
L
L
Hansen
INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif Paris South University, Villejuif IGR, Villejuif.
M
M
Boutron-Ruault
INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif Paris South University, Villejuif IGR, Villejuif.
A
A
Racine
INSERM, Research Centre 'Lipids, Nutrition, Cancer', Dijon, France.
V
V
Cottet
German Cancer Research Center (DKFZ), Heidelberg, Germany.
R
R
Kaaks
German Cancer Research Center (DKFZ), Heidelberg, Germany.
T
T
Kühn
Hellenic Health Foundation, Athens WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
A
A
Trichopoulou
Hellenic Health Foundation, Athens WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
C
C
Bamia
Hellenic Health Foundation, Athens WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
A
A
Naska
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
S
S
Grioni
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence.
D
D
Palli
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples.
S
S
Panico
Cancer Registry and Histopathology Unit, 'Civile - M.P. Arezzo' Hospital, ASP, Ragusa.
R
R
Tumino
School of Public Health and HuGeF Foundation, Torino, Italy The School of Public Health, Imperial College London, London, UK.
P
P
Vineis
The School of Public Health, Imperial College London, London, UK National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands Department of Gastroenterology and Hepatology.
H B
HB
Bueno-de-Mesquita
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
H
H
van Kranen
The School of Public Health, Imperial College London, London, UK Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
P H
PH
Peeters
Department of Community Medicine, Faculty of Health Sciences, UIT The Arctic University of Norway, Tromsø Department of Research, Cancer Registry of Norway, Oslo, Norway Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Genetic Epidemiology, Samfundet Folkhälsan, Helsinki, Finland.
E
E
Weiderpass
Basque Regional Health Department, Public Health Direction and Biodonostia Research Institute (CIBERESP), San Sebastian.
M
M
Dorronsoro
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona.
P
P
Jakszyn
Andalusian School of Public Health, Granada CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada.
M
M
Sánchez
Public Health Directorate, Asturias, Oviedo.
M
M
Argüelles
CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid Department of Epidemiology, Regional Health Council, Murcia.
J M
JM
Huerta
Public Health Institute of Navarra, Pamplona Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain.
A
A
Barricarte
Department of Biobank Research, Umeå University, Umeå, Sweden International Agency for Research on Cancer (IARC-WHO), Lyon, France.
M
M
Johansson
Department of Radiation Sciences, Oncology, University of Umeå, Umeå, Sweden.
I
I
Ljuslinder
University of Cambridge School of Clinical Medicine, Cambridge.
K
K
Khaw
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
N
N
Wareham
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
H
H
Freisling
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
T
T
Duarte-Salles
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
M
M
Stepien
The School of Public Health, Imperial College London, London, UK.
M J
MJ
Gunter
The School of Public Health, Imperial College London, London, UK.
E
E
Riboli
D000368:Aged; D001622:Betaine / Q000097:blood*; D016022:Case-Control Studies; D002794:Choline / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood*; D008875:Middle Aged; D009752:Nutritional Status / Q000502:physiology*; D011446:Prospective Studies; D012307:Risk Factors; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000097:blood
D001622:Betaine; C025138:dimethylglycine; D008715:Methionine; D002794:Choline; D012521:Sarcosine
betaine; choline; colorectal cancer risk; dimethylglycine; methionine; population-based case–control study