A Missense Polymorphism in the PTPN13 Gene (rs989902) Associated with the Risk of Colorectal and Gastric Cancers in an Iranian Population

Abstract Background/aim Given that phosphorylation/dephosphorylation of many important proteins at tyrosine residues play a vital role in various cellular functions, it can be inferred that protein tyrosine phosphatase enzymes, including the protein tyrosine phosphatase non-receptor type 13 (PTPN13), are involved in numerous critical cellular processes. PTPN13 influences several signaling pathways and biological activities, suggesting a potential role in carcinogenesis. This study aimed to select the most relevant PTPN13 polymorphism using “polymorphism selection index” (PSI) and investigate its association with gastric (GC) and colorectal (CRC) cancer risk. Methods Missense polymorphisms with minor allele frequency ≥ 0.01 were retrieved and PSI was calculated for each. We conducted two case-control studies in an Iranian population (197 CRC/215 controls; 150 GC/230 controls). Genotyping was carried out by PCR-RFLP. Associations with cancer risk were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Results Among seven missense polymorphisms, rs989902 (T > G, Y2081D) had the highest PSI and was selected. Consequently, we focused on investigating the association between this polymorphism and the risk of CRC and GC. The GG genotype was found to increase the risk of both cancers (for CRC: OR = 2.36, 95% CI = 1.18–4.69, p = 0.014; for GC: OR = 2.14, 95% CI = 1.06–4.31, p = 0.033). Conclusion This study demonstrates that the rs989902 is significantly associated with the risk of CRC and GC in an additive manner. Furthermore, the cancer risk elevated with an increasing number of combined risk factors, including the rs989902-GG genotype, smoking, and family history of cancer, highlighting the importance of this genetic variant in the etiology of these malignancies.