Polymorphism in the interleukin-17A promoter contributes to gastric cancer

AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.

Cytotoxic effect of methanolic extracts of Fritillaria imperialis bulbs and Eryngium caucasicum leaves on hepatoma and colon cancer cells

Objective: To evaluate antitumor activities of Fritillaria imperialis and Eryngium caucasicum methanolic extracts on human hepatoma (HepG2) and colon cancer (HCT116) cell lines in comparison to human foreskin fibroblasts as the normal cells. Methods: Methanolic extracts of Fritillaria imperialis and Eryngium caucasicum were prepared by the maceration method. The effect of the extracts at various concentrations (100, 200, 400, 600, and 800 μg/mL) on cell survival was evaluated using the MTT method. Besides, fluorescence staining was used to evaluate death patterns of the cells. Results: MTT assay showed that Fritillaria imperialis significantly decreased the viability of all cell lines after 24 and 48 hours of treatments. However, Eryngium caucasicum extract did not show any significant cytotoxicity effect on the cell lines. Fluorescence staining revealed that Fritillaria imperialis induced apoptosis of HCT116 cells at 550 μg/mL. Conclusions: Fritillaria imperialis extract has antiproliferative and cytotoxic effects on HCT116 and HepG2 cancer cells and therefore, may serve as an anticancer agent.

Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk

AIM:To investigate the association of the inducible nitric oxide synthetase(iNOS) C150T polymorphism with Helicobacter pylori(H.pylori) infection and gastric cancer(GC) risk in Iran.METHODS:In order to determine whether there was a correlation between iNOS genotype and GC in Iran,we conducted a case-control study using samples from 329 individuals.For each sample,the C150T iNOS polymorphism was genotyped by polymerase chain reaction(PCR) and restriction digestion.Patients were grouped by cancer presence,demographic and behavior characteristics,and H.pylori infection status.Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population.RESULTS:In this population,we found that smoking,hot beverage consumption,a familial history of GC and H.pylori infection status were significantly associated with GC development(P = 0.015,P < 0.001,P = 0.0034,and P < 0.015,respectively).The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone,but was impacted by H.pylori infection status.When compared to the non-H.pylori infected group,cancer patients who had a heterozygous CT genotype and were also infected with H.pylori were 2.1 times more at risk of developing GC [odds ratio(OR) = 2.1,P = 0.03] while those with a homozygous TT genotype and infected with H.pylori were 5.0 times more at risk of developing GC(OR = 5.0,P = 0.029).In contrast,this association was not seen in patients in the control group.CONCLUSION:A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility.

Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease

AIM:To evaluate the diagnostic accuracy of serum Immunoglobulin A(IgA)for differentiating early stage nonalcoholic fatty liver disease(NAFLD)from nonalcoholic steatohepatitis(NASH).METHODS:All cases had fatty liver change confirmed by ultrasound and aminotransferases of at least twice the normal level.Clinical and biochemical data,including serum IgA,were obtained from 50 histologically proven NAFLD cases and 54 healthy controls.Fasting whole blood samples were obtained from the study population.Immunoturbidimetric methods were used to measure the IgA levels.All NAFLD cases were hospitalized for liver biopsy.Liver specimens were examined for steatosis,steatohepatitis and fibrosis within hepatocytes.Patients were categorized into two groups:NASH and non-NASH.Variables were compared within cases(NASH vs non-NASH)and controls.Cut-off values of serum IgA were evaluated using analysis of receiver operating characteristic(ROC curves).Associations between the variables were tested using calculations of correlation coefficients.Statistical significances were assigned to P values<0.05.RESULTS:The extent of liver fibrosis correlated positively with IgA levels.Subjects with no fibrosis in their liver biopsies had a lower IgA level(301.5±91.2 mg/dL)than subjects with any degree of fibrosis(388.8±140.8 mg/dL),(P=0.01).IgA levels were higher in NASH cases,and its value was significantly higher for higher degrees of fibrosis.Patients with perisinusoidal or pericellular fibrosis had significantly higher levels of IgA(403.5±133.9 mg/dL,418.2±129.5 mg/dL)compared to those without it(301.8±94.9 mg/dL,297.7±91.5 mg/dL),respectively.No significant correlation was found between steatosis grade and serum IgA levels.Based on ROC analysis,the best predictive IgA cutoff value for detecting liver fibrosis was 360mg/dL(61%sensitivity,81%specificity).CONCLUSION:The serum IgA level is useful to evaluate the severity of liver fibrosis and can be used serially for evaluation and follow-up of NAFLD cases.

Response to Abadi and Kusters, World J Gastroenterol 19: 429-430

In a recent study, Rafiei et al, reported a link between a C150T polymorphism in the human inducible nitric oxide gene and Helicobacter pylori infection as a risk factor for gastric cancer among an Iranian population. Subsequently, Abadi and Kusters published a letter to the editor questioning the validity of the study because of a supposed flaw in primer design. Here we respond to the claims of Abadi and Kusters and show that the results reported in the original article are valid.