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Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

We investigated the association between incidence of various cancers and four single nucleotide polymorphisms (SNPs), two each in two protein tyrosine phosphatase (PTP) genes, PTPRJ and PTPN13, by a case–control study conducted in Japan.

Methods

The study samples comprised 819 cancer-free controls and 569 cancer cases including lung, head and neck, colorectal, and esophageal cancers.

Results

Compared with the major homozygotes at the Arg326Gln SNP in PTPRJ, a likely homologue of the mouse SCC1 (susceptible to colon cancer), Arg/Gln or Gln/Gln genotypes exhibited an increased colorectal cancer risk with adjusted odds ratios (aOR) of 1.71 (P = 0.021) and 3.74 (P = 4.14 × 10−4), respectively. Increased risks were observed with one or more of the combination genotypes of Gln276Pro and Arg326Gln in PTPRJ for most cancer types (aOR range 10.13–55.08, Bonferroni-corrected P = 0.0454–7.20 × 10−9). In the PTPN13, major homozygotes of Ile1522Met showed an increased risk for lung squamous cell carcinomas (aOR 1.86), compared to the heterozygotes. Increased risks were observed with at least one of the combination genotypes of the two SNPs, Ile1522Met and Tyr2081Asp, for all but esophageal cancer examined (aOR 3.36–13.75), compared with double heterozygotes. Moreover, these high risks were seen also when all cancer cases were combined (aOR 1.81–6.84).

Conclusions

PTPRJ and PTPN13 SNPs were found to influence susceptibility to a wide spectrum of cancers. Because allelic frequencies of these SNPs are relatively common in many ethnic groups, these findings are worthy of further study.

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Acknowledgments

Thanks are due to the surgeons of Okayama University Hospital for their cooperation. We also acknowledge Dr. Y. Kusaka of Kusaka Hospital (Bizen, Okayama), for his great help. We appreciate Dr. J. B. Cologne for his excellent advise on biostatistical analyses and on the manuscript preparation. This study was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan; (12213084).

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Authors and Affiliations

  1. Department of Molecular Genetics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama, 700-8558, Japan

    Yuichiro Mita, Yukiko Yasuda, Akiko Sakai, Mamoru Ouchida & Kenji Shimizu

  2. Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama, 700-8558, Japan

    Hiromasa Yamamoto & Shinichi Toyooka

  3. Department of Oral Pathology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama, 700-8558, Japan

    Mehmet Gunduz

  4. Department of Digestive Tract Surgery, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama, 700-8558, Japan

    Shunsuke Tanabe & Yoshio Naomoto

Authors
  1. Yuichiro Mita
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  2. Yukiko Yasuda
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  3. Akiko Sakai
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  4. Hiromasa Yamamoto
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  7. Shunsuke Tanabe
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  9. Mamoru Ouchida
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  10. Kenji Shimizu
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Correspondence to Kenji Shimizu.

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Mita, Y., Yasuda, Y., Sakai, A. et al. Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers. J Cancer Res Clin Oncol 136, 249–259 (2010). https://doi.org/10.1007/s00432-009-0656-7

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  • DOI: https://doi.org/10.1007/s00432-009-0656-7

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