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Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3
Author(s) -
Henao Olga L.,
Piyathilake Chandrika J,
Waterbor John W.,
Funkhouser Ellen,
Johanning Gary L.,
Heimburger Douglas C.,
Partridge Edward E.
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20695
Subject(s) - methylenetetrahydrofolate reductase , cervical intraepithelial neoplasia , methionine synthase , reductase , genetics , methionine , biology , medicine , enzyme , cervical cancer , genotype , gene , biochemistry , cancer , amino acid
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 B 12 , 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. © 2004 Wiley‐Liss, Inc.