One-carbon metabolism biomarkers and risk of colon and rectal cancers.
BACKGROUND
Folate intake has been associated with reduced colorectal cancer risk; however, few studies have prospectively examined circulating folate or other related one-carbon biomarkers.


METHODS
We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 50- to 69-year-old Finnish men to investigate associations between serum folate, vitamin B6, vitamin B12, riboflavin, and homocysteine and risk of colon and rectal cancers. Controls were alive and cancer-free at the time of case diagnosis and matched 1:1 on age and date of baseline fasting serum collection with cases (152 colon and 126 rectal cancers). Multivariate-adjusted odds ratios and 95% confidence intervals were calculated using conditional logistic regression.


RESULTS
Serum vitamin B6 was inversely associated with colon cancer [odds ratio, 0.30 (95% confidence interval, 0.11-0.82) in the highest versus lowest quintile]. An increased risk of colon cancer was suggested for men in the middle quintile of serum folate, but without indication of a dose-response relationship. None of the other serum biomarkers were associated with colon or rectal cancer, and we observed no interactions with alcohol consumption or methionine or protein intake. A priori combinations of the five one-carbon serum biomarkers provided no clear evidence to support a collective influence on colorectal cancer risk.


CONCLUSIONS
Our results support the hypothesis that higher vitamin B6 status may play a role in inhibiting colon cancer carcinogenesis; however, folate and other one-carbon related biomarkers were not associated with colon or rectal cancer.
Weinstein
Stephanie J
SJ
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Nutritional Epidemiology Branch, Suite 320, 6120 Executive Boulevard, Bethesda, MD 20892, USA. weinstes@mail.nih.gov
Albanes
Demetrius
D
Selhub
Jacob
J
Graubard
Barry
B
Lim
Unhee
U
Taylor
Philip R
PR
Virtamo
Jarmo
J
Stolzenberg-Solomon
Rachael
R
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000517:prevention & control; D004311:Double-Blind Method; D005387:Finland / Q000453:epidemiology; D005492:Folic Acid / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011322:Primary Prevention; D012306:Risk; D012307:Risk Factors; D025101:Vitamin B 6 / Q000097:blood*
D014408:Biomarkers, Tumor; D010919:Placebos; D025101:Vitamin B 6; D005492:Folic Acid