Folate metabolism, a complex pathway required for either the synthesis of DNA precursors or for DNA methylation reactions, has been frequently suggested to play a key role in colorectal cancer (CRC) pathogenesis. In the present study we collected 96 CRC individuals (55 males /41 females, mean age71.04 years) and 96 healthy matched controls (53 males / 43 females, mean age 70.86 years) to further investigate the determinants of folate metabolism in both CRC patients and healthy matched controls. All the individuals have been genotyped for nine biallelic polymorphism of genes involved in folate metabolism (MTHFR 677C > T, MTHFR 1298A > C, MTR 2756A > G, MTRR 66A > G, SLC 19A1 80G > A, TYMS 28bp 2R/3R, TYMS 1494 6bp ins/del, DNMT3B - 579 G > T, DNMT3B - 149C > T). In addition, we also measured plasma homocysteine (hcy), serum folate, and serum vitamin B12 levels in those subjects that were not taking drugs or supplements known to interfere with those parameters. Multifactorial analysis of variance revealed significantly decreased serum folate (P=0.04)and plasmahcy (P=0.02) levels in CRC patients with respect to healthy matched controls. In addition, vitamin B12 levels had a significant effect on serum folate concentrations (P=0.04), whilst a significant contributor of plasma hcy levels was age at sampling (P=0.0001). Concerning the polymorphisms of metabolic genes, none of them showed significant different Distributions between CRC patients and healthy controls. However, the MTRR 66A>G polymorphism was associated with serum folate levels in both CRC and healthy individuals (AA vs. GG, P<0.05), the SLC19A1 80G>A polymorphism showed a significant correlation with hcy levels in our population (GG vs. AA, P<0.05), and the DNMT3B-579G >T polymorphism resulted associated with serum vitamin B12 levels (GG vs. GT, P<0.05). Present results suggest that complex interactions among folate, hcy, vitaminB12, and polymorphisms of metabolic genes, superimposed on age related declines, might be responsible of the impairments of folate metabolism in CRC patients

Determinants of folate metabolism in colorectal cancer patients and healthy individuals

COPPEDE', FABIO;LOPOMO, ANGELA;FAILLI, ALESSANDRA;LEGITIMO, ANNALISA;CONSOLINI, RITA;SPISNI, ROBERTO;MIGLIORE, LUCIA
2014

Abstract

Folate metabolism, a complex pathway required for either the synthesis of DNA precursors or for DNA methylation reactions, has been frequently suggested to play a key role in colorectal cancer (CRC) pathogenesis. In the present study we collected 96 CRC individuals (55 males /41 females, mean age71.04 years) and 96 healthy matched controls (53 males / 43 females, mean age 70.86 years) to further investigate the determinants of folate metabolism in both CRC patients and healthy matched controls. All the individuals have been genotyped for nine biallelic polymorphism of genes involved in folate metabolism (MTHFR 677C > T, MTHFR 1298A > C, MTR 2756A > G, MTRR 66A > G, SLC 19A1 80G > A, TYMS 28bp 2R/3R, TYMS 1494 6bp ins/del, DNMT3B - 579 G > T, DNMT3B - 149C > T). In addition, we also measured plasma homocysteine (hcy), serum folate, and serum vitamin B12 levels in those subjects that were not taking drugs or supplements known to interfere with those parameters. Multifactorial analysis of variance revealed significantly decreased serum folate (P=0.04)and plasmahcy (P=0.02) levels in CRC patients with respect to healthy matched controls. In addition, vitamin B12 levels had a significant effect on serum folate concentrations (P=0.04), whilst a significant contributor of plasma hcy levels was age at sampling (P=0.0001). Concerning the polymorphisms of metabolic genes, none of them showed significant different Distributions between CRC patients and healthy controls. However, the MTRR 66A>G polymorphism was associated with serum folate levels in both CRC and healthy individuals (AA vs. GG, P<0.05), the SLC19A1 80G>A polymorphism showed a significant correlation with hcy levels in our population (GG vs. AA, P<0.05), and the DNMT3B-579G >T polymorphism resulted associated with serum vitamin B12 levels (GG vs. GT, P<0.05). Present results suggest that complex interactions among folate, hcy, vitaminB12, and polymorphisms of metabolic genes, superimposed on age related declines, might be responsible of the impairments of folate metabolism in CRC patients
http://www.gastrojournal.org/article/S0016-5085(14)63939-1/abstract
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/817248
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