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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

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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.

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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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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, East–West Neo Medical Center, Kyunghee University College of Medicine, Seoul, Korea

    Seo-yun Tong & Jong Min Lee

  2. Cancer Epidemiology Branch, National Cancer Center, 111, Jungbalsan-ro, Madu-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do, 411-769, Korea

    Mi Kyung Kim

  3. College of Medicine, Korea University, Seoul, Korea

    Jae Kwan Lee

  4. Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA

    Sang Woon Choi

  5. University of Verona School of Medicine, Verona, Italy

    Simonetta Friso

  6. The Inha University, Incheon, Korea

    Eun-Seop Song

  7. Gil Medical Center, Gachon University of Medicine and Science, Inchon, Korea

    Kwang Beom Lee

  8. Ajou University School of Medicine, Suwon, Korea

    Jung Pil Lee

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  1. Seo-yun Tong
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Correspondence to Mi Kyung Kim.

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Tong, Sy., Kim, M.K., Lee, J.K. et al. 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. Cancer Causes Control 22, 63–72 (2011). https://doi.org/10.1007/s10552-010-9675-6

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  • DOI: https://doi.org/10.1007/s10552-010-9675-6

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