Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12.
OBJECTIVE
We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer.


METHODS
This multicenter case-control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20-75 years).


RESULTS
Patients with cervical cancer had significantly lower median serum folate and vitamin B12 concentrations vs. controls. Higher serum folate was significantly associated with lower cervical cancer risk (p for linear trend = 0.0058) with a trend for a lower CIN risk after multivariate adjustment. Low folate and the MTHFR 677 C > T variant were associated with a higher risk for CIN2/3 and cervical cancer vs. wild-type or heterozygous genotypes with high folate [OR, 2.39 (1.18-4.85) and 3.19 (1.43-7.13)]. Low vitamin B12 and the MTHFR 677 C > T variant also were associated with a higher risk for CIN 2/3 and cervical cancers [OR, 2.52 (1.17-5.42) and 2.40 (1-5.73)] vs. wild-type or heterozygous status with high vitamin levels.


CONCLUSIONS
Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.
Department of Obstetrics and Gynecology, East-West Neo Medical Center, Kyunghee University College of Medicine, Seoul, Korea.
Seo-yun
SY
Tong
Mi Kyung
MK
Kim
Jae Kwan
JK
Lee
Jong Min
JM
Lee
Sang Woon
SW
Choi
Simonetta
S
Friso
Eun-Seop
ES
Song
Kwang Beom
KB
Lee
Jung Pil
JP
Lee
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000097:blood*; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D014805:Vitamin B 12 / Q000097:blood*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000201:enzymology / Q000235:genetics*
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12