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ABSTRACT: Epidemiological and experimental evidence indicates chronic inflammation as a risk factor for colorectal cancer. We investigated whether IL-1B -511C>T (rs16944), IL-1B +3954C>T (rs1143634) and IL1-RN +2018T>C (rs419598) cytokine polymorphisms are correlated with colorectal cancer. Blood samples were obtained from 377 Romanian subjects: 144 patients with sporadic colorectal cancer and 233 healthy controls. Polymorphisms were analyzed by allelic discrimination TaqMan PCR assays with specific probes. The results of our study showed that IL-1RN +2018T>C polymorphism is associated with colorectal cancer. We found that there was a significant difference in the frequency of CC genotype between patients with colorectal cancer and the control group (OR 2.42, 95 % CI: 1.06-5.53, p = 0,034) when TT genotype was used as reference. Furthermore, in a stratified analysis, a positive association was found only for IL-1RN +2018CC genotype, that was limited to early I and II stages (OR 2.72, 95 % CI: 1.05-7.03, p = 0,033). We did not find any association between any of the IL-1B polymorphisms and colorectal cancer. In conclusion this study found that IL-1RN +2018T>C polymorphism is associated with colorectal cancer, mainly for localized disease.
Molecular Biology Reports 11/2012; · 2.93 Impact Factor
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ABSTRACT: INTRODUCTION: Angiogenesis is essential for the local growth, invasion and metastasis of the tumours. Vascular endothelial growth factors (VEGFs) play a crucial role in tumour angiogenesis. The aim of our study was to quantify the expression of several VEGF family molecules in human gastro-oesophageal cancers and to analyse possible correlations between genes expression and clinico-pathological features. MATERIALS AND METHODS: Gene expression was quantified in 43 gastro-oesophageal paired samples using qRT-PCR with TaqMan probes specific to VEGF-A, including soluble transcript variants and VEGF-B genes. RESULTS: VEGF-A, including the studied splice variants and VEGF-B mRNAs were expressed in both tumour and peritumour mucosa. The expression of VEGF-A and its isoforms was higher in tumour compared with paired peritumour mucosa, while no significant difference was observed in VEGF-B expression. VEGF-A expression tended to correlate with tumour invasion. CONCLUSION: VEGF-A has a tendency to over-express in gastro-oesophageal cancers, while VEGF-B does not seem involved in these tumours. Further studies are required to establish the utility of anti-VEGF-A therapy and to find biomarkers for pathogenesis or response to therapy in gastro-oesophageal tumours.
Clinical and Translational Oncology 08/2012; · 1.33 Impact Factor
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ABSTRACT: Gastric cancer remains one of the most common types of cancer worldwide, with a large geographical variation in incidence and mortality rates. Cytokine polymorphisms are the most studied host polymorphisms and are associated with an increased risk of stomach cancer in many regions, but have not been studied extensively in Eastern European populations.
To investigate the potential association between five cytokine promoter polymorphisms (interleukin [IL] 1b -511C→T [rs16944], IL-4 receptor [IL-4R] -3223C→T [rs2057768], IL-8 -251T→A [rs4073], IL-10 -1082A→G [rs1800896] and tumour necrosis factor-alpha -308G→A [rs1800629]) and susceptibility to gastric adenocarcinoma in a Romanian population.
A total of 347 subjects, consisting of 105 patients with gastric adenocarcinoma and 242 controls, were included. All cytokine polymorphisms were genotyped using allele-specific, commercially available probes. Hardy-Weinberg equilibrium in both groups was analyzed using the chi squared test, and the relationship between targeted polymorphisms and the risk of gastric cancer was estimated using OR and 95% CI.
A significant association between the IL-4R -3223C→T polymorphism and risk of gastric cancer was found. Carriers of the IL-4R -3223TT genotype were at a 2.5-fold increased risk for gastric cancer (OR 2.51 [95% CI 1.08 to 5.84]; P=0.041). Moreover, the presence of the IL-4R -3223TT genotype was associated with an increased risk of noncardia gastric adenocarcinoma (OR 3.08 [95% CI 1.25 to 7.58]; P=0.023). No associations were found among the other polymorphisms.
The results suggest that the IL-4R -3223C→T polymorphism may increase the risk of gastric adenocarcinoma, mainly for the noncardia type, in the Romanian population.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 08/2012; 26(8):532-6. · 1.21 Impact Factor
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ABSTRACT: The study aimed to assess the possible association of polymorphisms in the autophagy gene IRGM (rs13361189 and rs4958847) with the risk of gastric cancer.
A total of 102 patients with gastric adenocarcinoma, 52 with chronic gastritis and 351 healthy controls were included in this study. IRGM allelic variants were genotyped by quantitative real-time polymerase chain reaction. The association between polymorphisms and gastric cancer risk was estimated by odds ratios (OR) and 95% confidence interval (CI).
A significant difference was found for rs4958847 A allele. Carriers of the A allele were protected against gastric cancer (OR = 0.58, 95% CI 0.35-0.97, P = 0.038). Moreover, the presence of this allele seems to play an important role in decreasing the risk for the intestinal type of gastric cancer (OR = 0.47, 95% CI 0.23-0.94, P = 0.03). In contrast, the rs13361189 IRGM polymorphism was not associated with susceptibility to gastric cancer. None of the targeted polymorphisms were associated with chronic gastritis.
IRGM rs4958847 polymorphism influences susceptibility to gastric cancer, mainly for the intestinal type.
Journal of Digestive Diseases 07/2012; 13(7):360-5. · 1.59 Impact Factor
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Advances in Clinical and Experimental Medicine 01/2011; 20(4):423-429. · 0.09 Impact Factor
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ABSTRACT: Colorectal carcinoma is the second leading cause of death by cancer in Europe as its incidence increases with life span. Continuing research to detect new highly sensitive and specific noninvasive biomarkers is essential. The aim of this study was to compare 9 mismatching repair (MMR) genes activation levels in normal, polyp and malignant tissues in order to detect a MMR gene expression pattern in sporadic colorectal malignant pathology.
MMR mRNA levels were evaluated in tumor-normal tissue paired samples and polyps collected from 29 patients undergoing standard surgical procedures with curative intention. Real-Time quantitative Reverse Transcription PCR (qRT PCR) with TaqMan probes specific to ANKRD17, EXO1, MLH1, MLH3, MSH2, MSH3, MSH4, MSH5, MSH6 gene transcripts were used.
The general tendency observed was a lower mRNA level of MMR genes in tumor samples compared with the normal tissue, with the exception of EXO1 gene. The number of patients that showed a higher expression of MMR genes in normal tissue was significantly greater than the number of patients that showed a higher expression inside the tumor (p=0.0024). ANKRD17 mRNA levels were higher in normal tissue than in tumor for 16 cases, by contrast with only 6 cases of higher mRNA levels in tumor.
ANKRD17 mRNA appears to be the most sensitive target and may have a potential value as an additional marker for the existing multitarget assay panel for colorectal cancer detection.
Journal of gastrointestinal and liver diseases: JGLD 06/2010; 19(2):155-9. · 1.81 Impact Factor
