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Low folate levels may protect against colorectal cancer
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.ORCID-id: 0000-0001-9581-3845
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2006 (Engelska)Ingår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, nr 10, s. 1461-1466Artikel i tidskrift (Övrigt vetenskapligt) Published
Abstract [en]

BACKGROUND AND AIMS: Dietary folate is believed to protect against colorectal cancer (CRC). However, few studies have addressed the role of circulating levels of folate. The aim of this study was to relate prediagnostic plasma folate and homocysteine concentrations and the methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C polymorphisms to the risk of developing CRC.

SUBJECTS: Subjects were 226 cases and 437 matched referents from the population based Northern Sweden Health and Disease Cohort.

RESULTS: We observed a bell-shaped association between plasma folate concentrations and CRC risk; multivariate odds ratio for middle versus lowest quintile 2.00 (95% confidence interval (CI) 1.13-3.56). In subjects with follow up times greater than the median of 4.2 years however, plasma folate concentrations were strongly positively related to CRC risk; multivariate odds ratio for highest versus lowest quintile 3.87 (95% CI 1.52-9.87; p trend = 0.007). Homocysteine was not associated with CRC risk. Multivariate odds ratios for the MTHFR polymorphisms were, for 677 TT versus CC, 0.41 (95% CI 0.19-0.85; p trend = 0.062), and for 1298 CC versus AA, 1.62 (95% CI 0.94-2.81; p trend = 0.028). Interaction analysis suggested that the result for 1298A>C may have been largely due to linkage disequilibrium with 677C>T. The reduced CRC risk in 677 TT homozygotes was independent of plasma folate status.

CONCLUSIONS: Our findings suggest a decreased CRC risk in subjects with low folate status. This possibility of a detrimental component to the role of folate in carcinogenesis could have implications in the ongoing debate in Europe concerning mandatory folate fortification of foods.

Ort, förlag, år, upplaga, sidor
2006. Vol. 55, nr 10, s. 1461-1466
Nationell ämneskategori
Gastroenterologi
Identifikatorer
URN: urn:nbn:se:umu:diva-15280DOI: 10.1136/gut.2005.085480PubMedID: 16638790OAI: oai:DiVA.org:umu-15280DiVA, id: diva2:154952
Tillgänglig från: 2007-11-23 Skapad: 2007-11-23 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Folate in cancer and cardiovascular disease: prospective studies from the population-based northern Sweden health and disease study
Öppna denna publikation i ny flik eller fönster >>Folate in cancer and cardiovascular disease: prospective studies from the population-based northern Sweden health and disease study
2006 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

BACKGROUND: Folate, a B-vitamin found primarily in fruits and vegetables, especially leafy greens, and other B-vitamins involved in folate metabolism are believed to protect against cancer and cardiovascular disease. Maintaining an adequate folate status ensures availability of methyl groups for DNA synthesis and for all methylation reactions in the body, and prevents the accumulation of homocysteine, a sulphur-containing amino acid that has been linked to cardiovascular disease. The aim of this thesis was to relate factors involved in folate metabolism to the risk of developing colorectal cancer (CRC), prostate cancer (PCa), stroke (ischemic and hemorrhagic), and acute myocardial infarction (AMI).

SUBJECTS AND METHODS: These were nested case-referent studies, with 226 CRC, 254 PCa, 396 stroke (334 ischemic and 62 hemorrhagic), and 571 AMI cases, and double, matched referents from the population-based Northern Sweden Health and Disease Study.

CRC RESULTS: A bell-shaped association was observed between plasma folate concentrations and the risk of CRC [multivariate odds ratio (OR) for the middle versus lowest quintile, 2.00 (95% CI 1.13-3.56)]. Homocysteine was not associated with CRC risk. A reduced risk was observed for the MTHFR 677C>T polymorphism [OR for TT versus CC, 0.41 (95% CI 0.19-0.85), Ptrend=0.062] that was independent of plasma folate status. Prediagnostic plasma folate concentrations were higher in cases with promoter hypermethylation in the p16 and/or hMLH1 tumor suppressor genes in CRC tissue compared to cases without promoter hypermethylation in these genes (P=0.025).

PCa RESULTS: Increasing plasma levels of folate and vitamin B12 were associated with increased risk of PCa [OR for the highest versus lowest quartile, 1.60 (95% CI 1.03-2.49), Ptrend=0.02 for folate, and 2.63 (95% CI 1.61-4.29), Ptrend<0.001 for vitamin B12]. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance. In multivariate analyses, the risk estimate remained statistically significant only for vitamin B12.

STROKE RESULTS: Plasma folate concentrations were associated with the risk of hemorrhagic stroke in an inverse linear manner after adjustment for conventional risk factors including hypertension [multivariate OR for the highest versus lowest quartile, 0.21 (95% CI 0.06-0.71), Ptrend=0.008]. Risk estimates were attenuated by the inclusion of homocysteine in the model [OR 0.34 (95% CI 0.08-1.40), Ptrend=0.088]. Similar results were obtained for folate intake. Neither plasma folate levels nor folate intake demonstrated a clear association with the risk of ischemic stroke, and neither plasma nor dietary vitamin B12 was associated with the risk of either type of stroke.

AMI RESULTS: Plasma folate concentrations demonstrated an inverse association with risk of AMI that was independent of other risk factors, including homocysteine [multivariate OR for the highest versus lowest quintile, 0.56 (95% CI 0.34-0.90), Ptrend=0.080]. For vitamin B12, no clear risk relationships were apparent. None of the risk estimates for dietary intake of folate, vitamin B12, vitamin B6, or vitamin B2 were statistically significant, although the results for folate and vitamin B12 intake were in line with those for the plasma variables.

CONCLUSIONS: The results of these population-based, prospective studies suggest that although a high folate status may be associated with a reduced risk of cardiovascular diseases, the relationship with cancer risk seems to be more complicated. The possibility of a detrimental component to the role of folate and vitamin B12 in carcinogenesis may have implications in the ongoing debate concerning mandatory folate fortification of foods.

Ort, förlag, år, upplaga, sidor
Umeå: Medicinsk biovetenskap, 2006. s. 91
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1049
Nationell ämneskategori
Klinisk laboratoriemedicin
Forskningsämne
medicinsk biokemi
Identifikatorer
urn:nbn:se:umu:diva-850 (URN)91-7264-159-2 (ISBN)
Disputation
2006-09-22, Hörsal Betula, 6M, Umeå, 13:00 (Engelska)
Opponent
Tillgänglig från: 2006-09-04 Skapad: 2006-09-04 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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