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EZH2 genetic variants affect risk of gastric cancer in the Chinese Han population

Authors

  • Yuan Zhou,

    1. Key Lab of Genome Research of Anhui Province, Anhui Medical University, Hefei, China
    2. Department of Biology, Anhui Medical University, Hefei, China
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  • Wei-Dong Du,

    Corresponding author
    1. Key Lab of Genome Research of Anhui Province, Anhui Medical University, Hefei, China
    2. Department of Pathology, Anhui Medical University, Hefei, China
    3. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
    4. Sektion Experimentelle Anaesthesiologie, Universitaetsklinikum Ulm, Ulm, Germany
    • Correspondence to: Key Lab of Genome Research of Anhui Province, Anhui Medical University, Meishan Road 81, Hefei 230032, China.

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  • Qiang Wu,

    1. Department of Pathology, Anhui Medical University, Hefei, China
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  • Yi Liu,

    1. Department of Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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  • Gang Chen,

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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  • Jian Ruan,

    1. Key Lab of Genome Research of Anhui Province, Anhui Medical University, Hefei, China
    2. Department of Pathology, Anhui Medical University, Hefei, China
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  • Song Xu,

    1. Key Lab of Genome Research of Anhui Province, Anhui Medical University, Hefei, China
    2. Department of Pathology, Anhui Medical University, Hefei, China
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  • Feng Yang,

    1. Department of Pathology, Anhui Medical University, Hefei, China
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  • Fu-Sheng Zhou,

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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  • Xian-Fa Tang,

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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  • Hua-Yang Tang,

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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  • Xian-Bo Zuo,

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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  • Feng-Yu Zhang,

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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  • Liang-Dan Sun,

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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  • Xue-Jun Zhang

    1. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui Medical University, Hefei, China
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Abstract

Enhancer of zeste 2 (EZH2) gene encodes a histone methyltransferase that constitutes the catalytic component of the polycomb repressive complex-2 (PRC2) to initiate epigenetic silencing of genes. It is reported that the expression level of EZH2 in gastric cancer tissue was highly correlated with tumor progression, however, whether EZH2 genetic variants were associated with the risk of gastric cancer remains yet unknown. In this study, we conducted a genotyping analysis for EZH2 in 311 cases of gastric cancer and 425 controls from the Chinese Han population. We found five single nucleotide polymorphisms (SNP; rs12670401, rs6464926, rs2072407, rs734005, and rs734004) of EZH2 gene were significantly associated with the risk of gastric cancer. Of which, the rs12670401 with the minor allele C and rs6464926 with the minor allele T revealed strong associations with increased gastric cancer risk [P = 0.009, adjusted odds ratio (aOR) = 1.327, 95% CI = 1.075–1.683 and P = 0.012, aOR = 1.310, 95% CI = 1.059–1.619]. The other three SNPs, rs2072407, rs734005, and rs734004 contributed to significantly reduced risk of gastric cancer (P = 0.033, aOR = 0.787, 95% CI = 0.633–0.981, P = 0.045, aOR = 0.799, 95% CI = 0.642–0.995 and P = 0.048, aOR = 0.803, 95% CI = 0.645–0.999), respectively. We further found that rs12670401 and rs6464926 were in a strong LD while rs2072407, rs734005, and rs734004 were in another. Haplotype analysis of the five SNPs showed that haplotype CCTCT reduced the risk of gastric cancer (P = 0.031 and aOR = 0.784), while haplotype GTCTC significantly elevated the risk of gastric cancer (P = 0.011 and aOR = 1.310). We concluded that EZH2 variants were significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of EZH2 gene variants in carcinogenesis of gastric cancer of the Chinese Han population. © 2012 Wiley Periodicals, Inc.

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