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

Yuichiro Mita, Yukiko Yasuda, Akiko Sakai, Hiromasa Yamamoto, Shinichi Toyooka, Mehmet Gunduz, Shunsuke Tanabe, Yoshio Naomoto, Mamoru Ouchida, Kenji Shimizu

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

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, Bonferronicorrected 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.

Original languageEnglish
Pages (from-to)249-259
Number of pages11
JournalJournal of cancer research and clinical oncology
Volume136
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • Cancer
  • PTPN13
  • PTPRJ
  • SNP

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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