Introduction: Gastrointestinal cancers are among the most common cancers worldwide. Since some viral infections are carcinogenic, they may lead to gastrointestinal tract (GIT) neoplasms. This study aimed at investigating the relationship of GIT with John Cunningham Virus (JCV), Herpes Simplex virus (HSV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and Human Papillomavirus (HPV).

Methods: The present study was conducted at two educational centers (Ghaem and Imam Reza hospitals) in Mashhad, Iran, on a case group including 81 patients with such GIT cancers as stomach (n = 26), esophagus (n = 28), and colorectal (n = 27), and a control group including 81 subjects with gastrointestinal complaints without GIT cancers. The DNA of viruses was detected using Real-Time PCR.

Results: The results revealed that JCV and HPV infections were significantly expressed in patients with colorectal cancer (CRC), compared to healthy control subjects. The frequency of EBV and HPV in participants with gastric cancer (GC) was significantly higher than that in those in the control group, and JCV infection was more frequent in esophageal cancer (EC) relative to healthy subjects. JCV infection significantly increased the odds of CRC and EC incidence by 11.8 and 10.2 folds, respectively, compared to the healthy participants. In addition, EBV and HPV were associated with a 10.8 and 6.7-fold higher risk of GC or CRC, respectively.

Conclusions: The findings of the present study suggest that JCV, EBV, and HPV infections can be correlated with the risk of gastrointestinal cancers; however, gastrointestinal cancers showed no correlation with HSV and CMV.

Introduction: β-catenin plays a major role in colorectal carcinoma (CRC) development. This study aims at investigating the rate of β-catenin expression using immunohistochemistry in CRC among Jordanian patients, comparing different β-catenin compartmentalization in cell membrane, cytoplasm, and nuclei in different grades and stages of CRC, and examining the relationship of β-catenin expression with the clinicopathological features and survival.

Methods: This retrospective, cross sectional study included 63 CRC cases, and investigated the percentage of membranous, cytoplasmic, and nuclear β-catenin positivity using β-Catenin 14 Mouse Monoclonal Antibody on tissue microarray blocks prepared from archived paraffin blocks.

Results: Membranous positivity was observed in 96.8%, cytoplasmic in 69.8%, and nuclear in 36.5% of cases. There was a strong correlation between cytoplasmic and nuclear positivity (Pearson's coefficient = 0.71). There was a significant correlation between M stage and cytoplasmic staining (p = 0.047), but no significant correlation between M stage and nuclear staining (p = 0.42). There was no correlation between cytoplasmic or nuclear expression and sex, age or tumor site or type. There was no difference of survival between positive and negative cases (Log Rank test p = 0.849 for cytoplasmic staining and 0.915 for nuclear staining).

Conclusion: This study documents high expressions of cytoplasmic and nuclear β-catenin in CRC (69.8% and 36.5%, respectively). Furthermore, it shows a trend of higher expression in association with poor prognostic factors such as metastasis and lymph node involvement.

Introduction: Individuals with cancer face an elevated risk of subsequent tumors following their initial malignancy. However, the etiology of this secondary occurrence remains unclear.

Patients and Methods: A cohort of 2,707 participants underwent human leukocyte antigen (HLA) testing. We analyzed the incidence and survival outcomes of multiple primary malignancies (MPMs), subsequent metachronous MPMs (sM-MPMs), and gastric malignancy (GM) in the remnant stomach (GMRS) as post-therapeutic GMs. We identified human endogenous retroviruses (HERV) gene-derived peptides (HHPs) from four previous studies, predicted candidate amino acid sequences of human immunodeficiency virus and HHPs, and matched them to candidate genes through a peptide search in UniProt.

Results: Among the participants, 311 (11.5%) were diagnosed with an MPM and 161 (6.3%) with an sM-MPM, and both groups exhibited unfavorable survival outcomes, whereas 289 (13.1%) with GMRS showed favorable survival. Patients with HLA-A31, with or without an MPM/sM-MPM, demonstrated either favorable or unfavorable survival, respectively, compared with those without this antigen. Furthermore, patients harboring HLA-A31-restricted HHP “NEQIVIGR,” which matched to human endogenous retrovirus-H long terminal repeat (LTR)-associating 2 (HHLA2), exhibited good survival but increased risks of both an MPM and sM-MPM. Conversely, HLA-A31/-B39/-B46-restricted HHPs “ILVPSAILA” and “EAMNTTSLL,” matching to HHLA2 and HHLA1, respectively, were associated with unfavorable survival and decreased risks of both an MPM and sM-MPM.

Conclusion: Our findings elucidate a novel pathogenesis of MPM, sM-MPM, and GMRS. Understanding the mechanisms underlying the correlation between HLA/HERV-encoded peptide interactions and the pathogenesis of these malignancies will yield new candidates for cancer therapies from a unique perspective.