Association between Serum Vitamin B12 and Global DNA Methylation in Colorectal Cancer Patients

Boughanem, Hatim; Hernández‐Alonso, Pablo; Tinahones, Alberto; Babió, Nancy; Salas‐Salvadó, Jordi; Tinahones, Francisco J.; Macías-González, Manuel

doi:10.3390/nu12113567

Cited by 28 publications

(19 citation statements)

References 39 publications

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“…Remarkably, LINE-1 methylation levels have been proposed as a biomarker of weight loss in obese subjects, influenced by dietary antioxidant capacity [ 80 ]. In our study, LINE-1 methylation was nominally associated with the availability of circulating B12, demonstrating the relevance of this vitamin for epigenetic homeostasis and genome stability, as previously hypothesized [ 81 ]. This methylation mark was not directly associated with methylation in the MTFHR gene, despite both being lower in the overweight/obese group than in the control group.…”

Section: Discussionsupporting

confidence: 83%

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Bordoni

Petracci

Młodzik-Czyżewska

et al. 2022

Oxidative Medicine and Cellular Longevity

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Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one-carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal-weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group ( p = 1.3 ∗ 10 − 5 ). A high BMI was associated with lower LINE-1 ( p = 0.004 ) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation ( p = 0.047 ). mtDNAcn was lower in overweight/obese subjects ( p = 0.004 ) and independently correlated with MTHFR methylation levels ( p = 0.005 ) but not to LINE-1 methylation levels ( p = 0.086 ). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal-weight subjects, it was nominally correlated with homocysteine levels ( p = 0.035 ) and MTHFR methylation ( p = 0.033 ). This evidence suggests that increased body weight might perturb mitochondrial-nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one-carbon cycle.

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Section: Discussionsupporting

confidence: 83%

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Bordoni

Petracci

Młodzik-Czyżewska

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…A recent study demonstrated a higher serum B12 was associated with tumour-specific hypomethylation in CRC patients, suggestive of B12-driving epigenetic alterations leading to carcinogenesis. 34 Also, of relevance, is that vitamin b12 can be produced by the gut microbiome and that competition of b12 may affect the gut microbiome, which offers a further putative mechanistic link with colorectal cancer. 35 A possible carcinogenic effect of high serum vitamin B12 status has previously been observed in lung cancer 36 and possibly epithelial ovarian cancer, 37 but not in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Genetically predicted circulating B vitamins in relation to digestive system cancers

et al. 2021

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Background Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. Methods Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. Results Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. Conclusions These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.

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“…The same proves true for other dietary components, such as polyphenols [ 113 ] vitamins [ 114 , 115 , 116 ], and minerals [ 116 , 117 ] alone or in combination.…”

Section: Nutrients Epigenetics and Colorectal Cancermentioning

confidence: 73%

Dietary Factors Modulating Colorectal Carcinogenesis

et al. 2021

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The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies.

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Association between Serum Vitamin B12 and Global DNA Methylation in Colorectal Cancer Patients

Cited by 28 publications

References 39 publications

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Genetically predicted circulating B vitamins in relation to digestive system cancers

Dietary Factors Modulating Colorectal Carcinogenesis

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