title: Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3.
abstract: The role of nutrient-related genetic susceptibility factors for pre-cancerous lesions is gaining attention. We conducted a study to examine associations between polymorphisms in folate pathway coenzymes (methylenetetrahydrofolate reductase [MTHFR] and methionine synthase [MS]) and cervical intraepithelial neoplasia (CIN) 2 or 3 in a population exposed to folic acid by the food fortification program in the United States. Status of MTHFR and MS and circulating concentrations of folate, vitamins B12, A, E, C and total carotene were ascertained in 170 Caucasian and 266 African-American women positive for high-risk human papilloma virus (HR-HPV). Polymorphism status was determined using polymerase chain reaction assays. Micronutrient concentrations were measured using radiobinding assays, high performance liquid chromatography or spectrophotometry. Presence/absence of CIN 2 or 3 was determined on the basis of histology results and the association with risk factors was examined using multivariable analyses. Eighty women had CIN 2 or 3 lesions and they were compared to 356 women who had CIN 1, ASCUS or normal cytology. We found that women polymorphic for MTHFR were less likely to have CIN 2 or 3 (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.23-0.79). No associations were seen with MS polymorphism alone (OR = 0.72, 95% CI = 0.43-1.21); however, women polymorphic for both MTHFR and MS were less likely to have CIN 2 or 3 (OR = 0.21, 95% CI = 0.08-0.62). We conclude that these polymorphisms in the folate metabolic pathway were associated with a lower likelihood of CIN 2 or 3 in a population exposed to adequate amounts of folate from exposure to food fortification with folic acid.
authors.affiliation: Department of Epidemiology of the University of Alabama at Birmingham, Birmingham, AL, USA. ohenao@uab.edu
authors.forename: Olga L
authors.initials: OL
authors.lastname: Henao
authors.forename: Chandrika J
authors.initials: CJ
authors.lastname: Piyathilake
authors.forename: John W
authors.initials: JW
authors.lastname: Waterbor
authors.forename: Ellen
authors.initials: E
authors.lastname: Funkhouser
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johanning
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Heimburger
authors.forename: Edward E
authors.initials: EE
authors.lastname: Partridge
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011336:Probability; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase