Folate and MTHFR: risk of adenoma recurrence in the Polyp Prevention Trial.
BACKGROUND
Low dietary folate intake has been associated with colorectal cancer risk and adenoma recurrence. A C/T transition at position 677 in the gene encoding methlylenetetrahydrofolate reductase (MTHFR C677T) has been reported to interact with folate intake to modulate colorectal adenoma recurrence or cancer risk.


METHODS
We investigated the association between MTHFR, total folate, and the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. We compared 625 individuals with any adenoma recurrence after 4 years (266 individuals with multiple (> or =2) recurrent adenomas and 101 individuals with advanced adenoma recurrence) to 978 individuals with no adenoma recurrence. Odds ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were calculated using unconditional logistic regression. We also investigated effect modification of the MTHFR genotype associations by total folate intake.


RESULTS
In general, no statistically significant associations were found between quartile of folate intake (dietary or total) and adenoma recurrence. The MTHFR CT genotype was associated with a significantly increased risk of multiple adenoma recurrence (OR: 1.34, 95% CI: 1.00, 1.81). No significant interaction was noted for total folate and MTHFR genotype, though an increased risk of recurrence noted for the MTHFR CT genotype was statistically significant only for those individuals with below median intake of total folate.


CONCLUSIONS
We report that the MTHFR 677 CT genotype was associated with increased risk of adenoma recurrence (specifically multiple adenoma recurrence) 4 years after polypectomy.
Murphy
Gwen
G
Cancer Prevention Fellowship Program, Office of Preventive Oncology, Bethesda, MD, USA. murphygw@mail.nih.gov
Sansbury
Leah B
LB
Cross
Amanda J
AJ
Stolzenberg-Solomon
Rachael
R
Laiyemo
Adeyinka
A
Albert
Paul S
PS
Wang
Zhuoqiao
Z
Schatzkin
Arthur
A
Lehman
Teresa
T
Kalidindi
Aravind
A
Modali
Rama
R
Lanza
Elaine
E
D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000483:Alleles; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000235:genetics; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016017:Odds Ratio; D011795:Surveys and Questionnaires; D014803:Vitamin B Complex / Q000235:genetics
D014803:Vitamin B Complex; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)