title: Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.
abstract: In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1.
authors.affiliation: School of Chemical & Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur 613401, India. Electronic address: naushadsm@gmail.com.
authors.forename: Shaik Mohammad
authors.initials: SM
authors.lastname: Naushad
authors.affiliation: School of Chemical & Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur 613401, India.
authors.forename: M
authors.initials: M
authors.lastname: Janaki Ramaiah
authors.affiliation: School of Chemical & Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur 613401, India.
authors.forename: Manickam
authors.initials: M
authors.lastname: Pavithrakumari
authors.affiliation: School of Chemical & Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur 613401, India.
authors.forename: Jaganathan
authors.initials: J
authors.lastname: Jayapriya
authors.affiliation: Center of Excellence in Biotechnology Research, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Tajamul
authors.initials: T
authors.lastname: Hussain
authors.affiliation: Department of Biochemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Salman A
authors.initials: SA
authors.lastname: Alrokayan
authors.affiliation: Department of Surgical Oncology, Nizam's Institute of Medical Sciences, Hyderabad -500082, India.
authors.forename: Suryanarayana Raju
authors.initials: SR
authors.lastname: Gottumukkala
authors.affiliation: Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad 500082, India.
authors.forename: Raghunadharao
authors.initials: R
authors.lastname: Digumarti
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad 500082, India.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Kutala
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology / Q000379:methods; D004032:Diet; D004198:Disease Susceptibility / Q000378:metabolism*; D004843:Epistasis, Genetic; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005502:Food; D059647:Gene-Environment Interaction; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008875:Middle Aged; D016571:Neural Networks, Computer; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D015262:Xenobiotics; D005492:Folic Acid
keywords: Artificial neural network; Breast cancer; Folate pathway; Methylome; Xenobiotic pathway