title: Postdiagnostic intake of one-carbon nutrients and alcohol in relation to colorectal cancer survival.
abstract: BACKGROUND
  Observational data have suggested that intakes of nutrients involved in one-carbon metabolism are inversely associated with risk of colorectal carcinoma and adenomas. In contrast, results from some preclinical studies and cardiovascular and chemoprevention trials have raised concerns that high folate intake may promote carcinogenesis by facilitating the progression of established neoplasia.
  
  
  OBJECTIVE
  We tested the hypothesis that higher total folate intake (including food folate and folic acid from fortified foods and supplements) or other one-carbon nutrient intakes might be associated with poorer survival after a diagnosis of colorectal cancer.
  
  
  METHODS
  We used rectal and colon cancer cases within the following 2 US prospective cohort studies: the Nurses' Health Study and the Health Professionals Follow-Up Study. Biennial questionnaires were used to gather information on medical history and lifestyle factors, including smoking and alcohol consumption. B-vitamin and methionine intakes were derived from food-frequency questionnaires. Data on tumor molecular characteristics (including microsatellite instability, CpG island methylator phenotype, KRAS, BRAF, and PIK3CA mutations, and long interspersed nucleotide element 1 methylation level) were available for a subset of cases. We assessed colorectal cancer-specific mortality according to postdiagnostic intakes of one-carbon nutrients with the use of multivariable Cox proportional hazards regression models.
  
  
  RESULTS
  In 1550 stage I-III colorectal cancer cases with a median follow-up of 14.9 y, we documented 641 deaths including 176 colorectal cancer-specific deaths. No statistically significant associations were observed between postdiagnostic intakes of folate or other one-carbon nutrients and colorectal cancer-specific mortality (multivariate P-trend ≥ 0.21). In an exploratory molecular pathologic epidemiology survival analysis, there was no significant interaction between one-carbon nutrients or alcohol and any of the tumor molecular biomarkers examined.
  
  
  CONCLUSIONS
  Higher postdiagnostic intakes of one-carbon nutrients are not associated with the prognosis in stage I-III colorectal cancer. Our findings do not support the hypothesis that higher folate intake after colorectal cancer diagnosis might increase risk of cancer-related death.
authors.affiliation: Gastrointestinal Research Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom; plochhead@mgh.harvard.edu shuji_ogino@dfci.harvard.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Lochhead
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.affiliation: Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; and.
authors.forename: Yin
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sukawa
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;
authors.forename: Sun A
authors.initials: SA
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.affiliation: Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; and.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; and.
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.affiliation: Departments of Epidemiology and.
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.affiliation: Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital, Boston, MA; Channing Division of Network Medicine, Department of Medicine, and.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; Channing Division of Network Medicine, Department of Medicine, and.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; Department of Pathology, Brigham and Women's Hospital, Boston, MA plochhead@mgh.harvard.edu shuji_ogino@dfci.harvard.edu.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000378:metabolism; D015331:Cohort Studies; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016208:Databases, Factual; D004032:Diet / Q000009:adverse effects*; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D005494:Folic Acid Deficiency / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005500:Follow-Up Studies; D005527:Food, Fortified / Q000009:adverse effects; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology
chemical_list: D005492:Folic Acid
keywords: alcohol; colorectal carcinoma; micronutrients; public health; survivorship