Lower specific micronutrient intake in colorectal cancer patients with tumors presenting promoter hypermethylation in p16(INK4a), p4(ARF) and hMLH1.
BACKGROUND
The diversity of the Mediterranean diet and the heterogeneity of acquired epigenetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and promoter hypermethylation in genes implicated in the pathogenesis of these neoplasms (p16(INK4a), p14(ARF), hMLH1) and the interaction with methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism.


METHODS
For the molecular study, 120 CRC patients were analyzed for hMLH1 promoter methylation status and MTHFR genotyping. Dietary patterns and molecular data on p16(INK4a) and p14(ARF) methylation were obtained from previous studies with this populations.


RESULTS
Patients with methylation in p16(INK4a) consumed significantly less folate (p = 0.01), vitamin A (p = 0.01), vitamin B1 (p = 0.007), potassium (p = 0.03) and iron (p = 0.02) than controls. Patients with methylation in p14(ARF) or hMLH1 consumed significantly less vitamin A (p = 0.001 and p = 0.05, respectively).


CONCLUSIONS
These results support that certain micronutrients protect against colorectal neoplasia and emphasize the importance of considering the different molecular forms of CRC as etiologically distinct diseases.
Mas
Sergi
S
Department of Pharmacology, School of Medicine, IDIBAPS, University of Barcelona, Casanova 143, 08036 Barcelona, Spain.
Lafuente
M Jose
MJ
Crescenti
Anna
A
Trias
Manuel
M
Ballesta
Antonio
A
Molina
Rafael
R
Zheng
Shichun
S
Wiencke
John K
JK
Lafuente
Amalia
A
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004032:Diet; D005260:Female; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D018977:Micronutrients / Q000008:administration & dosage*; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; C501486:MLH1 protein, human; D018977:Micronutrients; D009687:Nuclear Proteins; D025803:Tumor Suppressor Protein p14ARF; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000070957:MutL Protein Homolog 1