Lower specific micronutrient intake in colorectal cancer patients with tumors presenting promoter hypermethylation in p16(INK4a), p4(ARF) and hMLH1.

ABSTRACT

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. PATIENTS AND 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). CONCLUSION: 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.