Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis.

Full Abstract

BACKGROUND &

AIMS:
Increasing evidence suggests that a low folate intake and impaired folate metabolism may be implicated in the development of gastrointestinal cancers. We conducted a systematic review with meta-analysis of epidemiologic studies evaluating the association of folate intake or genetic polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), a central enzyme in folate metabolism, with risk of esophageal, gastric, or pancreatic cancer.

METHODS:
A literature search was performed using MEDLINE for studies published through March 2006. Study-specific relative risks were weighted by the inverse of their variance to obtain random-effects summary estimates.

RESULTS:
The summary relative risks for the highest versus the lowest category of dietary folate intake were 0.66 (95% confidence interval [CI], 0.53-0.83) for esophageal squamous cell carcinoma (4 case-control), 0.50 (95% CI, 0.39-0.65) for esophageal adenocarcinoma (3 case-control), and 0.49 (95% CI, 0.35-0.67) for pancreatic cancer (1 case-control, 4 cohort); there was no heterogeneity among studies. Results on dietary folate intake and risk of gastric cancer (9 case-control, 2 cohort) were inconsistent. In most studies, the MTHFR 677TT (variant) genotype, which is associated with reduced enzyme activity, was associated with an increased risk of esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, noncardia gastric cancer, gastric cancer (all subsites), and pancreatic cancer; all but one of 22 odds ratios were >1, of which 13 estimates were statistically significant. Studies of the MTHFR A1298C polymorphism were limited and inconsistent.

CONCLUSIONS:
These findings support the hypothesis that folate may play a role in carcinogenesis of the esophagus, stomach, and pancreas.

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Author information

Author/s: Larsson, Susanna C (SC); Giovannucci, Edward (E); Wolk, Alicja (A);

Affiliation: Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden. susanna.larsson(-atsign-)ki.se

Journal and publication information

Publication Type: Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't

Journal: Gastroenterology (Gastroenterology), published in United States. (Language: eng)

Reference: 2006-Oct; vol 131 (issue 4) : pp 1271-83

Dates: Created 2006/10/10; Completed 2006/12/04;

PMID: 17030196, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adenocarcinoma - epidemiology; genetics; prevention & control
Carcinoma, Squamous Cell - epidemiology; genetics; prevention & control
Case-Control Studies
Esophageal Neoplasms - epidemiology; genetics; prevention & control
Folic Acid - blood; therapeutic use
Gastrointestinal Neoplasms - epidemiology; genetics; prevention & control

Humans
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Pancreatic Neoplasms - epidemiology; genetics; prevention & control
Polymorphism, Genetic
Risk Factors
Stomach Neoplasms - epidemiology; genetics; prevention & control

Associated Chemicals: Folic Acid (59-30-3) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20)

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