Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation.
BACKGROUND
Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas.


METHODS
The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association.


RESULTS
We found a borderline significant inverse association with plasma B(6) [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; P(trend) = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetrahydrofolate reductase -C677T and plasma B(2) on risk of all adenomas.


CONCLUSIONS
Our results suggest that high levels of PLP and B(2) may protect against colorectal adenomas.
Figueiredo
Jane C
JC
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Harlyne J Norris Cancer Research Tower, 1450 Biggy Street Room 1509B, Los Angeles CA 90033, USA. janefigu@usc.edu
Levine
A Joan
AJ
Grau
Maria V
MV
Midttun
Oivind
O
Ueland
Per M
PM
Ahnen
Dennis J
DJ
Barry
Elizabeth L
EL
Tsang
Shirley
S
Munroe
David
D
Ali
Iqbal
I
Haile
Robert W
RW
Sandler
Robert S
RS
Baron
John A
JA
D000236:Adenoma / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D000428:Alcohol Drinking / Q000009:adverse effects; D001241:Aspirin / Q000627:therapeutic use*; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D016012:Poisson Distribution; D011110:Polymorphism, Genetic; D012256:Riboflavin / Q000097:blood; D012306:Risk; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
D025101:Vitamin B 6; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12; D001241:Aspirin; D012256:Riboflavin