Association of IL-22 and IL-22RA1 gene variants in Iranian patients with colorectal cancer.

AIM: In the current study, it was hypothesized that single nucleotide polymorphisms (SNPs) in the regulatory region of the IL-22 signaling pathway genes, including IL-22 and IL-22RA1 variants, may be associated with CRC susceptibility. BACKGROUND: The important role of pro-inflammatory cytokines during tumorigenesis is well-established. In recent years, IL-22 has been linked with colorectal cancer (CRC) through a number of mechanistic and observational studies. METHODS: The association of four polymorphisms in the IL-22 (rs1179251 and rs1179246) and IL-22RA1 (rs4648936 and rs10794665) genes with CRC risk were studied using a case-control design with 304 cases and 345 controls from the Iranian population. All 649 subjects were evaluated by PCR-RFLP method. RESULTS: No significant difference was found in genotype and allele frequencies between the cases and controls for either IL-22 and IL-22RA1 gene variants or CRC risk before or after adjusting for confounders. CONCLUSION: The current findings do not present any significant evidence for associations between variants in IL-22 signaling pathway genes and CRC. Complementary studies with greater sample sizes may be necessary to fully elucidate the nature of these associations.

Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients.

The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location.

Prognostic Significance of Nuclear ß-Catenin Expression in Patients with Colorectal Cancer from Iran.

BACKGROUND: Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/ß-catenin pathway. Accumulation of nuclear ß-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear ß-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC. OBJECTIVES: In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated. PATIENTS AND METHODS: In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear ß-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant. RESULTS: The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of ß-catenin and 133 (80.6 %) were negative for ß-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear ß-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear ß-catenin positive expression profile were found to be younger than patients with negative nuclear ß-catenin expression (P = 0.010). Univariate and multivariate analysis showed that tumors with ß-catenin expression had a poorer prognosis compared to tumors without ß-catenin expression. CONCLUSIONS: According to our findings, the distribution of nuclear b-catenin expression is a poor prognostic marker in patients with colon cancer.

Lack of influence of the SMAD7 gene rs2337107 polymorphism on risk of colorectal cancer in an Iranian population.

SMAD7 has been identified as a functional candidate gene for colorectal cancer (CRC). SMAD7 protein is a known antagonist of the transforming growth factor beta (TGF-ß) signaling pathway which is involved in tumorigenesis. Polymorphisms in SMAD7 may thus alter cancer risk. The aim of this study was to investigate the influence of a SMAD7 gene polymorphism (rs2337107) on risk of CRC and clinicopathological features in an Iranian population. In total, 210 subjects including 105 patients with colorectal cancer and 105 healthy controls were recruited in our study. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of colorectal cancer and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs2337107 and the risk of colorectal cancer. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). Although there was not any association between genotypes and disorder, CT was the most common genotype in this population. This genotype prevalence was also higher in the patients with well grade (54.9%) and colon (72.0%) tumors. Our results provide the first evidence that this polymorphism is not a potential contributor to the risk of colorectal cancer and clinicopathological features in an Iranian population, and suggests the need of a large-scale case-control study to validate our results.

Phylogenetic analysis of hepatitis C virus strains and risk factors associated with infection and viral subtypes among Iranian patients.

Hepatitis C virus (HCV) has infected approximately 170 million people worldwide. While the seroprevalence of anti-HCV antibody among Iranian blood donors is 0.13%, HCV infection is prevalent in 59-80% of Iranian injecting drug users. One hundred seventy-eight anti-HCV positive patients were referred to the Gastroenterology Department at the Taleghani Hospital (Tehran, Iran) between June 2007 and June 2012. Out of 178 samples, 142 were positive for HCV-RNA. HCV subtypes were determined using phylogenetic analysis of the NS5B or 5'UTR/core regions. Of 142 viremic patients, 71 (50%) were infected with HCV subtype 1a, 43 (30.3%) with subtype 3a, 20 (14.1%) with subtype 1b, 3 (2.1%) with subtype 4d, 2 (1.4%) with subtype 4a, 1 (0.7%) with subtype 2b, and 1 (0.7%) with subtype 6a. Interestingly, genetic analysis of a sub-genomic fragment from one patient identified a non-subtypeable HCV genotype-3 strain. There was a significant association between HCV subtype and a history of injecting drug use (P = 0.003). Subtype 3a was predominant among patients with such a history. Injecting drug use was associated with younger age (P < 0.001). HCV subtype was also significantly associated with a history of upper gastrointestinal endoscopy (P = 0.02). Subtype 1a was more frequent among patients with such a history. In addition, history of upper gastrointestinal endoscopy was significantly associated with older age (P = 0.002). In conclusion, while HCV subtype 1a is predominant among infected Iranian individuals, subtype 3a is predominant among Iranian injecting drug users.

Association of co-stimulatory human B-lymphocyte antigen B7-2 (CD86) gene polymorphism with colorectal cancer risk.

AIM: This study investigated the role of CD86 +237 G/C polymorphism in intensifying the risk of CRC development. BACKGROUND: Colorectal cancer (CRC) is a multi-factorial diseases. Genetic background could affect the susceptibility of individuals to CRC development. CD86 is a co-stimulatory factor on antigen-presenting cells that plays key roles in several cancer related mechanisms such as autoimmunity, transplantation and tumor immunity. PATIENTS AND METHODS: A total of 300 individuals, 150 known CRC patients and 150 healthy control individuals, were subjected for the study. CD86 rs17281995 single nucleotide polymorphism (SNP) was genotyped using Allelic Discrimination method. RESULTS: A statistically significant difference was found among CD86 gene polymorphism (rs17281995) and risk of CRC development. The frequency of GG, GC and CC in control subjects was determined as 38%, 57.3% and 4.7% respectively and in CRC subjects were determined as 42%, 85% and 23% respectively. The data shows a significant association between CC genotype (P = 0.007) and C allele (P = 0.017) of the studied polymorphism and risk of CRC. CC genotype and C allele are also more frequent in female patients when the data is stratified according to gender status. CONCLUSION: Our results suggest that CD86 gene alteration could affect the individual's risk for developing CRC among Iranian population and could be used as an important prognostic factor associated with risk of CRC.