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Cancer Causes & Control

, Volume 22, Issue 1, pp 63–72 | Cite as

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

  • Seo-yun Tong
  • Mi Kyung Kim
  • Jae Kwan Lee
  • Jong Min Lee
  • Sang Woon Choi
  • Simonetta Friso
  • Eun-Seop Song
  • Kwang Beom Lee
  • Jung Pil Lee
Original paper

Abstract

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.

Conclusion

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.

Keywords

Folate Vitamin B12 Genetic polymorphisms Methylenetetrahydrofolate reductase Cervical intraepithelial neoplasia Cervical cancer 

Notes

Acknowledgments

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.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Seo-yun Tong
    • 1
  • Mi Kyung Kim
    • 2
  • Jae Kwan Lee
    • 3
  • Jong Min Lee
    • 1
  • Sang Woon Choi
    • 4
  • Simonetta Friso
    • 5
  • Eun-Seop Song
    • 6
  • Kwang Beom Lee
    • 7
  • Jung Pil Lee
    • 8
  1. 1.Department of Obstetrics and GynecologyEast–West Neo Medical Center, Kyunghee University College of MedicineSeoulKorea
  2. 2.Cancer Epidemiology BranchNational Cancer CenterGoyang-siKorea
  3. 3.College of MedicineKorea UniversitySeoulKorea
  4. 4.Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA
  5. 5.University of Verona School of MedicineVeronaItaly
  6. 6.The Inha UniversityIncheonKorea
  7. 7.Gil Medical CenterGachon University of Medicine and ScienceInchonKorea
  8. 8.Ajou University School of MedicineSuwonKorea

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