A case-control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis.
OBJECTIVE
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 1298A-->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.
Rao
Gautam G
GG
Division of Gynecologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75201, USA.
Kurien
Aleena
A
Gossett
Diana
D
Griffith
William F
WF
Coleman
Robert L
RL
Muller
Carolyn Y
CY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D014626:Vaginal Smears
D042965:Methylenetetrahydrofolate Reductase (NADPH2)