Baseline plasma total homocysteine and adenoma recurrence: results from a double blind randomized clinical trial of aspirin and folate supplementation.
BACKGROUND
Elevated plasma total homocysteine (tHcy) is an accepted marker of functional folate deficiency but may have independent effects on colorectal neoplasia risk. It is uncertain whether plasma tHcy is associated with risk at the low levels common in a folate-fortified population.


METHODS
Study subjects, about half of whom were recruited after fortification of grain products with folic acid in the United States and Canada, consisted of 871 individuals with a recent history of one or more colorectal adenomas who were randomized to receive either a 1 mg/day folic acid supplement or a placebo within one of three randomly assigned aspirin treatment groups (placebo, 81, or 325 mg/day). Nonfasting plasma tHcy was determined by a gas chromatograph mass chromatography method. We estimated adjusted risk ratios and 95% confidence intervals (95% CI) for one or more adenoma recurrences for each quartile of baseline plasma tHcy using generalized linear regression with an overdispersed Poisson approximation to the binomial.


RESULTS
The Q4/Q1 adjusted risk ratio for any adenoma was 0.98 (95% CI, 0.70-1.38; P trend = 0.17) in the placebo group, and 0.81 (95% CI, 0.58-1.12; P-trend = 0.17) in the folic acid group. Results were similar for adenomas with advanced features. There was no modification by sex, aspirin treatment group or MTHFR 677C>T genotype.


CONCLUSIONS
Plasma tHcy is not an independent marker for an increase in colorectal adenoma recurrence risk in postfortification populations in which plasma tHcy levels are in the lower range of values.


CONCLUSIONS
Controlling plasma tHcy levels is unlikely to favorably modify adenoma recurrence risk in folate-fortified populations.
Levine
A Joan
AJ
USC Keck School of Medicine, Department of Preventive Medicine, Genetic Epidemiology, NRT 1450 Biggy Street Room 1509A, Los Angeles, CA 90033, USA. ajoanlev@usc.edu
Grau
Maria V
MV
Mott
Leila A
LA
Ueland
Per Magne
PM
Baron
John A
JA
D000236:Adenoma / Q000097:blood* / Q000201:enzymology / Q000517:prevention & control; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000097:blood / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000201:enzymology / Q000517:prevention & control; D004311:Double-Blind Method; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000201:enzymology / Q000517:prevention & control; D011795:Surveys and Questionnaires; D055815:Young Adult
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D001241:Aspirin