MTHFR (C677T and A1298C) polymorphisms and risk of sporadic distal colorectal adenoma in the UK Flexible Sigmoidoscopy Screening Trial (United Kingdom).
OBJECTIVE
The purpose of this study was to further evaluate the role of low activity MTHFR variants as well as to explore interactive effects between alcoholic drink consumption and MTHFR variants and risk of distal colorectal adenomatous polyps.


METHODS
We examined the relationship between MTHFR C677T and A1298C gene polymorphisms and risk of distal adenomas in one of the largest case control studies of 946 polyp-free controls and 894 cases, all participants of the UK Flexible Sigmoidoscopy Screening Trial (UKFSS).


RESULTS
Investigation of the effect of the MTHFR C677T polymorphism in this large UKFSS study revealed no overall association on adenoma risk (P>0.05). However the MTHFR 1298C allele was linked, for the first time, to high risk adenomas, although in males only (odds ratio (OR) for A/C+C/C compared with A/A 1.55; 95% confidence interval (CI), 1.08-2.22; P=0.018).


CONCLUSIONS
In this, the largest study of these polymorphisms in relation to colorectal adenoma, there was no evidence for an interaction with alcohol in combination with the variant forms of MTHFR (P>0.05).
Mitrou
Panagiota N
PN
Dunn Human Nutrition Unit, MRC/Wellcome Trust Building, Hills Road, Cambridge, CB2 2XY, UK.
Watson
Mark A
MA
Loktionov
Alexandre S
AS
Cardwell
Christopher
C
Gunter
Marc J
MJ
Atkin
Wendy S
WS
Macklin
Christopher P
CP
Cecil
Tom
T
Bishop
Timothy D
TD
Primrose
John
J
Bingham
Sheila A
SA
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2) / Q000235:genetics*; D000236:Adenoma / Q000201:enzymology / Q000235:genetics*; D018256:Adenomatous Polyps / Q000235:genetics*; D000368:Aged; D000428:Alcohol Drinking; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012812:Sigmoidoscopy / Q000379:methods
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2)