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
- 259 Downloads
We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer.
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).
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.
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.
KeywordsFolate Vitamin B12 Genetic polymorphisms Methylenetetrahydrofolate reductase Cervical intraepithelial neoplasia Cervical cancer
This work was supported in part by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MOST) (R01-2006-000-10621-0). The authors’ contributions to this work were as follows: KMK designed the study and obtained funding; ST and SHS drafted the manuscript; KMK, SWC, and SF contributed to the interpretation of the results and manuscript preparation; and JML, JKL, ESS, KBL, and JPL recruited subjects and collected the data. All authors approved the final manuscript. None of the authors report any conflict of interest.
- 1.Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37(8):S4–66Google Scholar
- 9.Goodman MT, McDuffie K, Hernandez B et al (2001) Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia. Cancer Epidemiol Biomark Prev 10(12):1275–1280Google Scholar
- 13.Duhr A, Galan P, Hercberg S (1991) Folate status and the immune system. Prog Food Nutr Sci 15:43–60Google Scholar
- 16.Alberg AJ, Selhub J, Shah KV, Viscidi RP, Comstock GW, Helzlsouer KJ (2000) The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine. Cancer Epidemiol Biomark Prev 9(7):761–764Google Scholar
- 25.Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M (1999) Methylenetetrahydrofolate reductase, diet, and risk of colon cancer. Cancer Epidemiol Biomark Prev 8(6):513–518Google Scholar
- 37.Cody RP, Smith JK (1997) Multiple-regression analysis. Applied statistics and the SAS programming language, 4th edn. Upper Saddle River, NJ, Prentice Hall, pp 235–247Google Scholar
- 43.von der Porten AE, Gregory JF III, Toth JP, Cerda JJ, Curry SH, Bailey LB (1992) In vivo folate kinetics during chronic supplementation of human subjects with deuterium-labeled folic acid. J Nutr 122(6):1293–1299Google Scholar