Dietary Vitamin B6 Intake and the Risk of Colorectal Cancer

Public Health Sciences, College of Medicine and Vet Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 01/2008; 17(1):171-82. DOI: 10.1158/1055-9965.EPI-07-0621
Source: PubMed


Vitamin B6, a coenzyme in the folate metabolism pathway, may have anticarcinogenic effects. Laboratory and epidemiologic studies support the hypothesis of its protective effect against colorectal cancer (CRC). The aim of this large Scottish case-control study, including 2,028 hospital-based cases and 2,722 population-based controls, was to investigate the associations between dietary and supplementary intake of vitamin B6 and CRC. Three logistic regression models adjusted for several confounding factors, including energy, folate, and fiber intake, were applied in the whole sample and after age, sex, cancer site, folate, MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), MTR A2756G (rs1805087), and MTRR A66G (rs1801394) stratification (analysis on genotypes on 1,001 cases and 1,010 controls < or =55 years old). Moderately strong inverse and dose-dependent associations in the whole sample were found between CRC risk and the intake of dietary and total vitamin B6 in all three models [model III: odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.61-0.98; P for trend = 0.03; OR, 0.86; 95% CI, 0.69-1.07; P for trend = 0.12]. In addition, meta-analyses of published studies showed inverse associations between vitamin B6 and CRC (combined relative risk, 0.81; 95% CI, 0.68-0.96; test for overall effect P = 0.01; combined odds ratio, 0.67; 95% CI, 0.60-0.75; test for overall effect P < 0.00001). Analysis within the stratified subgroups showed similar associations apart from a stronger effect among < or =55-year-old individuals. Evidence from larger cohort and experimental studies is now required to confirm and define the anticarcinogenic actions of vitamin B6 and to explore the mechanisms by which this effect is mediated.

Download full-text


Available from: Roseanne Cetnarskyj
  • Source
    • "France 2008 Matched case control Healthy persons 2002–2006 CRC Both 1,023/1,121 40.8 45.9 13.3 Yes 51.5 39.5 9 Yes Matched on age and sex Lightfoot et al. [58] United Kingdom 2008 Matched case control Hospital patients 1997–2000 CRC Both 468/734 45.8 46 8.3 Yes 48.6 43.7 7.8 Yes Adjusted for gender and age Mokarram et al. [59] Iran 2008 Case control Not reported 2003–2005 Colon Both 151/81 49.4 38.3 12.3 Yes Calculated OR, no adjustments Sharp et al. [60] United Kingdom (Scot- land) 2008 Matched case control Healthy persons 1998–2000 CRC Both 264/408 43.2 44.9 11.9 Yes 44.9 39.8 15.2 No Adjusted for age, gender, family history of CRC, physical activity, NAAID use, total energy intake, and type of dietary supplements Theodoratou et al. [61] Scotland 2008 Case control Healthy persons 1999–2006 CRC Both 2,028/ 2,722 45.3 45.0 11.5 Yes 45.8 44.1 10.1 Yes Adjusted for age, sex, deprivation score, and family history risk Zhang et al. [62] China 2008 Matched case control Hospital patients 2003–2005 CRC Both 300/300 30.4 46.5 23.1 Yes 65.3 29.7 5 Yes Adjusted for age, sex, education, family history, smoking, and drinking. El Awady et al. [63] Egypt 2009 Case control Healthy persons 2004–2007 CRC Both 35/68 65 29 6 Yes 38 54 8 Yes None reported Gallegos- Arreola et al. [30] Mexico 2009 Case control Healthy persons 2006–2008 CRC Both 369/170 33.6 34.1 32.2 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. The objective was to determine whether relationships exist between the methylene-tetrahydrofolate reductase (MTHFR) polymorphisms and risk of colorectal cancer (CRC) and examine whether the risk is modified by level of folate intake. Methods. MEDLINE, Embase, and SCOPUS were searched to May 2012 using the terms "folic acid," "folate," "colorectal cancer," "methylenetetrahydrofolate reductase," "MTHFR." Observational studies were included which (1) assessed the risk of CRC for each polymorphism and/or (2) had defined levels of folate intake for each polymorphism and assessed the risk of CRC. Results. From 910 references, 67 studies met our criteria; hand searching yielded 10 studies. The summary risk estimate comparing the 677CT versus CC genotype was 1.02 (95% CI 0.95-1.10) and for 677TT versus CC was 0.88 (95% CI 0.80-0.96) both with heterogeneity. The summary risk estimates for A1298C polymorphisms suggested no reduced risk. The summary risk estimate for high versus low total folate for the 677CC genotype was 0.70 (95% CI 0.56-0.89) and the 677TT genotype 0.63 (95% CI 0.41-0.97). Conclusion. These results suggest that the 677TT genotype is associated with a reduced risk of developing CRC, under conditions of high total folate intake, and this associated risk remains reduced for both MTHFR 677 CC and TT genotypes.
    Full-text · Article · Oct 2012 · Journal of Cancer Epidemiology
  • Source
    • "These studies were performed in a wide range of geographical settings leading to a diversity of racial groups. For the MTHFR C677T, 20 studies recruited Caucasians 4, 14-16, 18, 24-38; 11 studies examined individuals of Asian descent 25, 39-48; the remaining 10 studies were on Indians, Africans, Hawaiian, or mixed population. For the MTHFR A1298C, MTRR A66G, MTR A2756G analyses, 12, 6, and 7 studies were conducted in Caucasians, respectively, while 5, 3, and 3 studies were in Asians. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphisms in genes involved in folate metabolism may modulate the risk of colorectal cancer (CRC), but data from published studies are conflicting. The current meta-analysis was performed to address a more accurate estimation. A total of 41 (17,552 cases and 26,238 controls), 24(8,263 cases and 12,033 controls), 12(3,758 cases and 5,646 controls), and 13 (5,511 cases and 7,265 controls) studies were finally included for the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1289C, methione synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G polymorphisms and the risk of CRC, respectively. The data showed that the MTHFR 677T allele was significantly associated with reduced risk of CRC (OR = 0.93, 95%CI 0.90-0.96), while the MTRR 66G allele was significantly associated with increased risk of CRC (OR = 1.11, 95%CI 1.01-1.18). Sub-group analysis by ethnicity revealed that MTHFR C677T polymorphism was significantly associated with reduced risk of CRC in Asians (OR = 0.80, 95%CI 0.72-0.89) and Caucasians (OR = 0.84, 95%CI 0.76-0.93) in recessive genetic model, while the MTRR 66GG genotype was found to significantly increase the risk of CRC in Caucasians (GG vs. AA: OR = 1.18, 95%CI 1.03-1.36). No significant association was found between MTHFR A1298C and MTR A2756G polymorphisms and the risk of CRC. Cumulative meta-analysis showed no particular time trend existed in the summary estimate. Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test. Collectively, this meta-analysis suggested that MTHFR 677T allele might provide protection against CRC in worldwide populations, while MTRR 66G allele might increase the risk of CRC in Caucasians. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.
    Full-text · Article · Jun 2012 · International journal of biological sciences
  • Source
    • "In epidemiological studies, diets low in folate have been found to increase the risk of colon cancer.17–19 Other dietary factors, including methionine and vitamins B6 and B12, have been associated with colon cancer in some but not all epidemiological studies.7,11,19–21 Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism; it catalyzes the conversion of 5,10-methylenetetrahydrofolate (5,10-methylene-THF) to 5-methyltetrahydrofolate (5-methyl-THF).22 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), such as MTHFR C677T and A1298C, are associated with several cancers. This study aimed to evaluate the effects of MTHFR polymorphisms on colon cancer risk and possible interactions with environmental factors in a population from northeastern Thailand. This hospital-based case-control study was conducted during 2002-2006; 130 colon cancer cases and 130 age- and sex-matched controls were enrolled. Information was collected and blood samples were obtained for assay of MTHFR C677T and A1298C polymorphisms by polymerase chain reaction with restriction fragment length polymorphism techniques. Associations between variables of interest and colon cancer were assessed using conditional logistic regression. Increased risk of colon cancer was associated with alcohol consumption and bowel habits. Alcohol drinkers who consumed < or = 0.50 or >0.50 units of alcohol per day had elevated risks (OR(adj) = 3.5; 95% CI: 1.19-10.25 and OR(adj) = 1.71; 95% CI: 0.74-3.96, respectively). The risk was also higher in subjects with frequent constipation (11.69; 2.18-62.79) and occasional constipation (3.43; 1.72-6.82). An interaction was observed between the MTHFR C677T polymorphism and freshwater fish consumption on colon cancer risk (P value for interaction = 0.031). Interactions were observed between the MTHFR A1298C polymorphism and bowel habits, family history of cancer, alcohol consumption, and beef consumption on colon cancer risk (P-value for interaction = 0.0005, 0.007, 0.067, 0.003, respectively). In a Thai population, colon cancer risk was associated with alcohol and beef consumption, bowel habits, and family history of cancer. Interactions between MTHFR polymorphisms and environmental factors were also observed.
    Full-text · Article · Jul 2010 · Journal of Epidemiology
Show more