Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers.
OBJECTIVE
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 x 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 x 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.
Mita
Yuichiro
Y
Department of Molecular Genetics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Shikata-cho 2-5-1, Okayama, 700-8558, Japan.
Yasuda
Yukiko
Y
Sakai
Akiko
A
Yamamoto
Hiromasa
H
Toyooka
Shinichi
S
Gunduz
Mehmet
M
Tanabe
Shunsuke
S
Naomoto
Yoshio
Y
Ouchida
Mamoru
M
Shimizu
Kenji
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005973:Glutamine; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D007532:Isoleucine; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011392:Proline; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000235:genetics*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics; D012307:Risk Factors
D014408:Biomarkers, Tumor; D007532:Isoleucine; D005973:Glutamine; D001120:Arginine; D011392:Proline; D008715:Methionine; C516742:PTPN13 protein, human; C486288:PTPRJ protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3