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Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population

  • Original Paper
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Abstract

Purpose

Folate deficiency is considered to increase the risk of developing esophageal cancer. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism. A single C → T substitution at nucleotide 677 of the MTHFR cDNA influences enzyme activity. The purpose of this study is to compare the association of the MTHFR C677T polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC).

Methods

Using real-time PCR and melting curve analysis, the MTHFR C677T genotypes were determined in 430 patients with ESCC (241 German Caucasians and 189 northern Chinese) and 397 unrelated healthy controls (256 German Caucasians and 141 northern Chinese).

Results

A significant difference in MTHFR C677T genotype distribution was observed between German Caucasian controls (C/C, 41.8%, C/T, 44.9%, T/T, 13.3%) and northern Chinese controls (C/C, 17.7%, C/T, 38.3%, T/T, 44.0%) (χ2=52.19, P<0.001). The distribution of the MTHFR C677T genotypes among German ESCC patients (C/C, 39.0%, C/T, 48.1%, T/T, 12.9%) was not significantly different from that among healthy controls (χ2=0.531, P=0.767). In contrast, the frequency of the C/C genotype among Chinese ESCC patients (8.5%) was significantly lower than among Chinese healthy controls (17.7%) (χ2=6.37, P=0.012). The C/C genotype was correlated with a significantly reduced risk for the development of ESCC as compared to the combination of C/T and T/T genotypes (adjusted OR=0.38, 95% CI=0.16–0.88).

Conclusions

Our results suggest that, in contrast to German Caucasians, the MTHFR 677CC homozygous wild-type plays a protective role in the development of ESCC in the northern Chinese population.

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Fig. 1A,B

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Abbreviations

CI:

Confidence interval

ESCC:

Esophageal squamous cell carcinoma

MTHFR:

Methylenetetrahydrofolate reductase

OR:

Odds ratio

PCR:

Polymerase chain reaction

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Acknowledgements

We greatly acknowledge the expert technical assistance of Mrs. C. Pawlik, Mrs. H. Huss, and Mrs. B. Maruhn-Debowski. We also thank Miss Wei Guo, Mr. Ming He, Mr. Mingli Wu, Mr. Fanshu Meng, and Mr. Baoshan Zhao for their assistance in recruiting study subjects. This work was supported by the “Deutsche Krebshilfe” (grant number: 70–2964-Sa I) and the “Initiation Grant of Hebei Province”, China

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Authors and Affiliations

  1. Institute of Pathology, University of Düsseldorf, Germany

    Jianhui Zhang, Sybille Kiel & Helmut E. Gabbert

  2. Institute of Haemostasis and Transfusion Medicine, University of Düsseldorf, Germany

    Rainer B. Zotz

  3. Laboratory of Molecular Biology, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China

    Jianhui Zhang & Yan Li

  4. Department of Thoracic Surgery, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China

    Rui Wang

  5. Department of Urology, University of Düsseldorf, Germany

    Wolfgang A. Schulz

  6. Laboratory of Epidemiology, Hebei Cancer Institute, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China

    Denggui Wen & Zhifeng Chen

  7. Department of Endoscopy, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China

    Liwei Zhang & Shijie Wang

  8. Institute of Pathology, Technical University, Ismaninger Strasse 22, 81675, Munich, Germany

    Mario Sarbia

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  1. Jianhui Zhang
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Correspondence to Mario Sarbia.

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Zhang, J., Zotz, R.B., Li, Y. et al. Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population. J Cancer Res Clin Oncol 130, 574–580 (2004). https://doi.org/10.1007/s00432-004-0585-4

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  • DOI: https://doi.org/10.1007/s00432-004-0585-4

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