PTPRJ – Colorectal Cancer

PTPRJ has been evaluated as a candidate susceptibility gene for colorectal cancer based on murine mapping and human association studies. In a case–control series of 1,897 colorectal cancer patients and 1,954 controls, the common missense variant p.Arg326Gln showed no significant association with disease risk (homozygote OR 1.09, 95% CI 0.85–1.39) ([PMID:18843023]). Haplotype analyses of six tagging SNPs likewise failed to reveal a significant global effect on colorectal cancer susceptibility ([PMID:18843023]). In a separate Japanese cohort of 569 cases and 819 controls, Arg326Gln heterozygotes and homozygotes exhibited nominally increased risks (aOR 1.71 and 3.74, respectively), but these findings were not corroborated in larger follow-up studies ([PMID:19672627]).

Functional investigations of PTPRJ predominantly focus on tumor suppressor activity in other malignancies (e.g., glioma, meningioma) and on angiogenesis, without colon-specific in vitro or in vivo models. No familial segregation or high-penetrance germline mutations have been reported for colorectal cancer. Thus, current evidence supports only limited association of common PTPRJ variants with colorectal cancer risk, and PTPRJ is not yet a clinically actionable colorectal cancer predisposition gene.

Key Take-home: PTPRJ harbors common polymorphisms that have shown inconsistent, low-penetrance associations with colorectal cancer in population studies; monogenic risk evidence is lacking.

References

• Cancer epidemiology, biomarkers & prevention • 2008 • PTPRJ haplotypes and colorectal cancer risk. PMID:18843023
• Journal of cancer research and clinical oncology • 2010 • Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers. PMID:19672627

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