A case-control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis

Objectives. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene are thought to be associated with a varying risk of cervical dysplasia. The purpose of this trial was to study the role of the two common functional MHTFR polymorphisms in a large multiracial population at risk for cervical dysplasia and cancer. Methods. This is a nested case-control study of 376 subjects obtained from cohorts enrolled in an ongoing prospective cervical carcinogenesis protocol. Cases included invasive cancers (n = 51), and high (n = 50) and low (n = 50) grade dysplasia. There were 225 normal controls. Functional MTHFR 677C -> T and 1298A -> C genotypes were identified. Follow-up cytology data were reviewed for the control subjects from the time of study entry until August 2004. Results. There is a significant racial difference in allele frequency of the 677C -> T polymorphism (P < 0.005). African-American women had an extremely low prevalence of the 677T allele (8%). There was no significant difference in the frequency of the 677T allele between cases and controls. There is no racial difference in allele frequency of the 129SA -> C polymorphism. Also, no significant difference was found between cases and controls. Of the 51 cancers, no case was homozygous for both aberrant polymorphisms (677T, 1298C), and only 3 cases were heterozygous for both. Follow-up data were available for 129 of 225 control subjects (57%). Only 15 (12%) have had a subsequent abnormal pap, and there was no association with the 677C -> T polymorphism. Conclusions. We confirm a significant difference in the 677T allele frequencies among racial groups. However, there is no association of either the 677C -> T or 1298A -> C polymorphisms in cervical carcinogenesis. There is no role of the combined polymorphism effect in cervical cancer or evidence of prediction for future Pap abnormalities. (c) 2005 Elsevier Inc. All rights reserved.