title: Cross-talk between one-carbon metabolism and xenobiotic metabolism: implications on oxidative DNA damage and susceptibility to breast cancer.
abstract: The aim of this case-control study is to explore the role of aberrations in xenobiotic metabolism in inducing oxidative DNA damage and altering the susceptibility to breast cancer. Cytochrome P4501A1 (CYP1A1) m1 (OR: 1.41, 95% CI 1.08-1.84), CYP1A1 m4 (OR: 5.13, 95% CI 2.68-9.81), Catecholamine-O-methyl transferase (COMT) H108L (OR: 1.49, 95% CI 1.16-1.92), and glutathione S-transferase (GST) T1 null (OR: 1.68, 95% CI 1.09-2.59) variants showed association with breast cancer risk. Reduced folate carrier 1 (RFC1) 80A/CYP1A1 m1/CYP1A1 m4 and RFC1 80A/thymidylate synthase (TYMS) 5'-UTR 2R/methionine synthase (MTR) 2756G/COMT 108L genetic combinations were found to inflate breast cancer risk under the conditions of low dietary folate (345 ± 110 vs. 379 ± 139 μg/day) and low plasma folate (6.81 ± 1.25 vs. 7.09 ± 1.26 ng/ml) by increasing plasma 8-oxo-2'-deoxyguanosine (8-oxodG). This increase in 8-oxodG is attributed to low methionine (49.38 ± 23.74 vs. 53.90 ± 23.85 μmol/l); low glutathione (378 ± 242 vs. 501 ± 126 μmol/l) and GSTT1 null variant; and hypermethylation of CpG island of extracellular-superoxide dismutase (EC-SOD) (92.78 ± 11.49 vs. 80.45 ± 9.86%), which impair O-methylation of catechol estrogens to methoxy estrogens, conjugation of glutathione to semiquinones/quinones and free radical scavenging respectively. Our results suggest cross-talk between one-carbon metabolism and xenobiotic metabolism influencing oxidative DNA damage and susceptibility to breast cancer.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad 500082, Andhra Pradesh, India.
authors.forename: Shaik Mohammad
authors.initials: SM
authors.lastname: Naushad
authors.forename: Cheruku Apoorva
authors.initials: CA
authors.lastname: Reddy
authors.forename: Yedluri
authors.initials: Y
authors.lastname: Rupasree
authors.forename: Addepalli
authors.initials: A
authors.lastname: Pavani
authors.forename: Raghunadha Rao
authors.initials: RR
authors.lastname: Digumarti
authors.forename: Suryanarayana Raju
authors.initials: SR
authors.lastname: Gottumukkala
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Kutala
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D004249:DNA Damage; D004198:Disease Susceptibility / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D015262:Xenobiotics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015262:Xenobiotics; D002244:Carbon