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Functional polymorphisms in PIN1 promoter and esophageal carcinoma susceptibility in Chinese population

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Abstract

Peptidyl-prolyl cis–trans isomerase NIMA-interacting 1 (PIN1), which regulates the conformation of Pro-directed phosphorylation sites, has been identified as a critical catalyst involved in multiple oncogenic signaling pathways. Recently, it has been demonstrated that several putative functional polymorphisms of PIN1 gene were associated with cancer risk. This study examined whether genetic polymorphisms in promoter of PIN1 are associated with esophageal carcinoma susceptibility. Two common polymorphisms in PIN1, rs2233678 (−842G>C) and rs2233679 (−667C>T) were genotyped in this hospital-based case–control study of 699 esophageal carcinoma patients and 729 healthy controls. The results revealed that compared with the most common −842GG genotype carriers, the carriers of −842C variant genotypes (GC+CC) had significantly decreased risk of esophageal carcinoma [odds ratio (OR) = 0.55, 95 % CI = (0.40–0.75), P = 0.001]. No association was observed between the −667C>T polymorphism and the risk of esophageal carcinoma. Furthermore, we found that the haplotype of ‘C−842–C−667’ had a greater protected effect [OR = 0.67, 95 % CI = (0.47–0.96), P = 0.021]. Functional assay revealed that −842C variant genotypes (GC+CC) carriers had a lower transcription activity and mRNA expression level than the −842GG carriers. These results indicated that −842G>C genetic variant in PIN1 promoter may decrease the promoter activity, resulting in changes in the levels of PIN1 and modifying cancer susceptibility.

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Acknowledgments

This study was supported by the National Natural Scientific Foundation of China Grants 81001278, 81171895 and 81072366; A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Provincial Natural Science Foundation (No.BK2011297) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (No.20101561).

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The authors declare no competing interests.

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Authors and Affiliations

  1. Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, 215123, China

    Yonghe You, Jieqiong Deng, Jian Zheng, Lan Jiang, Na Li, Hongchun Wu, Wei Li & Yifeng Zhou

  2. Department of Cardiovascular and Thoracic Surgery, The First Affiliated Hospital, Soochow University, Suzhou, 215006, China

    Yonghe You & Bin Ni

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

    Jiachun Lu

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  1. Yonghe You
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  2. Jieqiong Deng
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  4. Lan Jiang
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  5. Na Li
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  10. Bin Ni
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Correspondence to Bin Ni.

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Yonghe You and Jieqiong Deng contributed equally to this study.

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You, Y., Deng, J., Zheng, J. et al. Functional polymorphisms in PIN1 promoter and esophageal carcinoma susceptibility in Chinese population. Mol Biol Rep 40, 829–838 (2013). https://doi.org/10.1007/s11033-012-2122-x

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  • DOI: https://doi.org/10.1007/s11033-012-2122-x

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