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Genetic variants A1826H and D2937Y in GAG-β domain of versican influence susceptibility to intestinal-type gastric cancer

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Abstract

Purpose

Versican regulates adhesion, migration, proliferation, and survival of cells, and plays an important role in cancer development. A case–control association study was performed to test genetic association of versican polymorphisms with susceptibility to gastric cancer.

Methods

In this study, 1,101 unrelated Korean subjects including 612 gastric cancer patients and 489 healthy controls were genotyped for all 21 exonic polymorphisms in the versican gene (VCAN) encoding amino acid changes in versican. Cancer susceptibility associations with the polymorphisms were assessed using multivariate logistic regression analysis with adjustment for age and gender and with control for multiple testing.

Results

Two amino acid changes in GAG-β domain of versican encoded by two almost fully correlated (r 2 = 0.97) nonsynonymous single-nucleotide polymorphisms in VCAN were associated with gastric cancer. The association was evident in intestinal-type but not in diffuse-type gastric cancer. The minor-allele homozygote of rs188703 (G > A, R1826H) or rs160277 (G > T, D2937Y) was significantly associated with a twofold decreased susceptibility to intestinal-type gastric cancer when compared with the other genotypes (adjusted odds ratio = 0.52 or 0.51, P = 0.0098 or 0.0087, respectively).

Conclusions

The intestinal-type gastric cancer susceptibility is associated with two amino acid changes of versican in the GAG-β domain, which is critical for enhancement of cell proliferation and activation of EGFR signal pathway by versican, and changes from the major to minor alleles may impair the function to decrease susceptibility to cancer.

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Abbreviations

CI:

Confidence interval

GAG:

Glycosaminoglycan

LD:

Linkage disequilibrium

OR:

Odds ratio

SNP:

Single-nucleotide polymorphism

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Acknowledgments

We appreciate Kyu-Sang Song for assistance in sample collection and Yikyeong Kim for technical and administrative assistance. This work was supported by grants from the Korea Healthcare Technology R&D Project [A084417]. H. Ju, B. Lim, M. Kim, and C. Kang are participants to the Brain Korea 21 Program. The sponsors had no role in design, performance or writing of the study.

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Authors and Affiliations

  1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 335 Gwahangno, Yuseong-gu, Daejeon, 305-701, Korea

    Hyoungseok Ju, Byungho Lim, Minjin Kim & Changwon Kang

  2. Department of General Surgery, Chungnam National University College of Medicine, Daejeon, 301-721, Korea

    Seung-Moo Noh

  3. Department of Medicine, Hanyang University Guri Hospital, Guri, 471-701, Korea

    Dong Soo Han

  4. Korea Gastric Cancer Center, Seoul Paik Hospital, Seoul, 100-032, Korea

    Hang-Jong Yu

  5. Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, 133-792, Korea

    Bo Youl Choi

  6. Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea

    Yong Sung Kim

  7. Department of Pathology, Seoul National University College of Medicine, Seoul, 110-744, Korea

    Woo Ho Kim

  8. Department of Laboratory Medicine, Eulji University College of Medicine, Daejeon, 302-120, Korea

    Chunhwa Ihm

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  1. Hyoungseok Ju
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Correspondence to Changwon Kang.

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Ju, H., Lim, B., Kim, M. et al. Genetic variants A1826H and D2937Y in GAG-β domain of versican influence susceptibility to intestinal-type gastric cancer. J Cancer Res Clin Oncol 136, 195–201 (2010). https://doi.org/10.1007/s00432-009-0647-8

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  • DOI: https://doi.org/10.1007/s00432-009-0647-8

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