Putatively functional polymorphisms of one-carbon and xenobiotic metabolic 
pathways influence susceptibility for wide spectrum of diseases. The current 
study was aimed to explore gene-gene interactions among these two metabolic 
pathways in four diseases i.e. breast cancer, systemic lupus erythematosus 
(SLE), coronary artery disease (CAD) and Parkinson's disease (PD). Multifactor 
dimensionality reduction analysis was carried out on four case-control datasets. 
Cross-talk was observed between one-carbon and xenobiotic pathways in breast 
cancer (RFC 80 G>A, COMT H108L and TYMS 5'-UTR 28 bp tandem repeat) and SLE 
(CYP1A1 m1, MTRR 66 A>G and GSTT1). Gene-gene interactions within one-carbon 
metabolic pathway were observed in CAD (GCPII 1561 C>T, SHMT 1420 C>T and MTHFR 
677 C>T) and PD (cSHMT 1420 C>T, MTRR 66 A>G and RFC1 80 G>A). These interaction 
models showed good predictability of risk for PD (The area under the receiver 
operating characteristic curve (C) = 0.83) and SLE (C = 0.73); and moderate 
predictability of risk for breast cancer (C = 0.64) and CAD (C = 0.63). 
Cross-talk between one-carbon and xenobiotic pathways was observed in diseases 
with female preponderance. Gene-gene interactions within one-carbon metabolic 
pathway were observed in diseases with male preponderance.