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A non-synonymous polymorphism Thr115Met in the EpCAM gene is associated with an increased risk of breast cancer in Chinese population

  • Epidemiology
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Abstract

As a tumor-associated antigen and a surface marker of breast cancer stem cells (BCSCs), epithelial cell adhesion molecule (EpCAM) plays an important role in not only cell adhesion, morphogenesis, metastases but also carcinogenesis. A non-synonymous C/T polymorphism (rs1126497) in exon3 of EpCAM causes a transition of 115 amino acid from Met to Thr. Another polymorphism (A/G, rs1421) in the 3′UTR causes loss of has-miR-1183 binding. A multiple independent case–control analysis was performed to assess the association between EpCAM genotypes and breast cancer risk. We observed that the variant EpCAM genotype (rs1126497 CT, and TT) was associated with substantially increased risk of breast cancer. Genotyping a total of 1643 individuals with breast cancer and 1818 control subjects in Eastern and Southern Chinese populations showed that rs1126497 CT + TT genotype had an odd ratio of 1.40 (95% confidence interval, 1.16–1.57) for developing breast cancer compared with CC genotype. The allele T increases the risk of breast cancer in a dose-dependent response manner (P trend < 0.001). Moreover, compared to breast cancer patients carrying the CC genotype, the EpCAM SNP rs1126497 CT or TT carrier was significantly associated with early breast cancer onset (P = 0.0023). However, no significant difference was found in genotype frequencies at the rs1421 A/G site between cases and controls. These findings suggest that M115T polymorphism in EpCAM may be a genetic modifier for developing breast cancer.

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Abbreviations

BMI:

Body mass index

CI:

Confidence interval

EpCAM:

Epithelial cell adhesion molecule

MAF:

Minor allele frequency

OR:

Odds ratio

SNP:

Single nucleotide polymorphism

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Acknowledgments

This study was supported by startup fund from Soochow University and grant 09KJD310006 from the University Science Foundation of Jiangsu Province (Dr. Y. Zhou), and partly supported by the National Natural Scientific Foundation of China grants 30671813 and 30872178 (Dr. J. Lu), and the Guangdong Provincial Scientific Research Grants 7003036 and 8251018201000005 (Dr. J. Lu). We thank Wangmin Zeng, Lei Yang, Ling Liu and Xiaoxuan Ling for their assistance in recruiting the subjects; and Hongjun Zhao and Sumei Feng for their laboratory assistance.

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Authors and Affiliations

  1. The Institute of Biology and Medical Sciences, Medical College of Soochow University, 215123, Suzhou, China

    Lan Jiang, Xiao Yu, Jian Zheng, Ping Zou, Yuting Li & Yifeng Zhou

  2. The Third Hospital Affiliated to Nantong University, Wuxi, China

    Chun Zhang

  3. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical College, 195 Dongfengxi Road, 510182, Guangzhou, China

    Yinyan Li, Xiaonong Bin & Jiachun Lu

Authors
  1. Lan Jiang
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  2. Chun Zhang
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Correspondence to Jiachun Lu or Yifeng Zhou.

Additional information

L. Jiang, C. Zhang, Y. Li, and X. Yu contributed equally to this work.

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Jiang, L., Zhang, C., Li, Y. et al. A non-synonymous polymorphism Thr115Met in the EpCAM gene is associated with an increased risk of breast cancer in Chinese population. Breast Cancer Res Treat 126, 487–495 (2011). https://doi.org/10.1007/s10549-010-1094-6

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  • DOI: https://doi.org/10.1007/s10549-010-1094-6

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