title: A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression.
abstract: The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL-odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC-OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL-OR = 9.8 (95% CI = 2.61 to 36.7); ICC-OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer.
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
authors.forename: Preethi N
authors.initials: PN
authors.lastname: Ragasudha
authors.forename: Jissa V
authors.initials: JV
authors.lastname: Thulaseedharan
authors.forename: Ramani
authors.initials: R
authors.lastname: Wesley
authors.forename: P G
authors.initials: PG
authors.lastname: Jayaprakash
authors.forename: Prema
authors.initials: P
authors.lastname: Lalitha
authors.forename: M Radhakrishna
authors.initials: MR
authors.lastname: Pillai
mesh_terms: D016022:Case-Control Studies; D004357:Drug Synergism; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007194:India / Q000453:epidemiology; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D054647:Nutrigenomics / Q000379:methods*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014805:Vitamin B 12 / Q000097:blood / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000097:blood / Q000494:pharmacology*
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12