Molecular Mechanisms Linking Genes and Vitamins of the Complex B Related to One-Carbon Metabolism in Breast Cancer: An In Silico Functional Database Study

Author:

Gálvez-Navas José María1234ORCID,Molina-Montes Esther135ORCID,Rodríguez-Barranco Miguel123ORCID,Ramírez-Tortosa MCarmen6ORCID,Gil Ángel367ORCID,Sánchez María-José123ORCID

Affiliation:

1. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain

2. Cancer Registry of Granada, Andalusian School of Public Health, Campus Universitario de Cartuja, Cuesta del Observatorio 4, 18011 Granada, Spain

3. Instituto de Investigación Biosanitaria ibs. GRANADA, Av. de Madrid, 18012 Granada, Spain

4. Ph.D. Program in Nutrition and Food Sciences, International Postgraduate School, University of Granada, Av. de Madrid 13, 18012 Granada, Spain

5. Department of Nutrition and Food Sciences, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18011 Granada, Spain

6. Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18011 Granada, Spain

7. Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 28029 Madrid, Spain

Abstract

Carcinogenesis is closely related to the expression, maintenance, and stability of DNA. These processes are regulated by one-carbon metabolism (1CM), which involves several vitamins of the complex B (folate, B2, B6, and B12), whereas alcohol disrupts the cycle due to the inhibition of folate activity. The relationship between nutrients related to 1CM (all aforementioned vitamins and alcohol) in breast cancer has been reviewed. The interplay of genes related to 1CM was also analyzed. Single nucleotide polymorphisms located in those genes were selected by considering the minor allele frequency in the Caucasian population and the linkage disequilibrium. These genes were used to perform several in silico functional analyses (considering corrected p-values < 0.05 as statistically significant) using various tools (FUMA, ShinyGO, and REVIGO) and databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO). The results of this study showed that intake of 1CM-related B-complex vitamins is key to preventing breast cancer development and survival. Also, the genes involved in 1CM are overexpressed in mammary breast tissue and participate in a wide variety of biological phenomena related to cancer. Moreover, these genes are involved in alterations that give rise to several types of neoplasms, including breast cancer. Thus, this study supports the role of one-carbon metabolism B-complex vitamins and genes in breast cancer; the interaction between both should be addressed in future studies.

Funder

Networking Biosanitary Research Center of Epidemiology and Public Health (CIBERESP)

Publisher

MDPI AG

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