The association between the survivin-31G/C promoter polymorphism and hepatocellular carcinoma risk in a Turkish population

WOS: 000298169300022PubMed ID: 21296634Background: Survivin, a member of the inhibitor of apoptosis protein family, functions as a key regulator of apoptosis and cell cycle regulation. A common single nucleotide polymorphism (-31G>C) at the survivin promoter has been extensively studied in various cancers and reported to influence survivin expression, but its association with hepatocellular carinoma (HCC) has yet to be investigated. The aim of the present study was to investigate whether this polymorphism could be involved in the risk of HCC susceptibilty. Methods: The genotype frequency of survivin -31G>C polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 160 subjects with HCC and 241 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: No statistically significant differences were found in the genotype distributions of the survivin -31G>C polymorphism among HCC and cancer-free control subjects (p = 0.28). Conclusion: Our results demonstrate for the first time that the survivin -31G/C polymorphism have not been any major role in genetic susceptibilty to hepatocellular carcinogenesis, at least in the population studied here. (C) 2011 Elsevier Ltd. All rights reserved.Cukurova UniversityCukurova University [FEF2008D4]The authors thank all the subjects who participated in this study. This work was supported by Cukurova University Research Fund FEF2008D4

CHEK2 1100delC, IVS2+1G > A and I157T mutations are not present in colorectal cancer cases from Turkish population

WOS: 000309818500018PubMed ID: 22521562Background: The cell cycle checkpoint kinase 2 (CHEK2) protein participates in the DNA damage response in many cell types. Germline mutations in CHEK2 (1100delC, IVS2+1G>A and I157T) have been impaired serine/threonine kinase activity and associated with a range of cancer types. This hospital-based case-control study aimed to investigate whether CHEK2 1100delC, IVS2+1G>A and I157T mutations play an important role in the development of colorectal cancer (CRC) in Turkish population. Methods: A total of 210 CRC cases and 446 cancer-free controls were genotyped for CHEK2 mutations by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-polymerase chain reaction (AS-PCR) methods. Results: We did not find the CHEK2 1100delC, IVS2+1G>A and I157T mutations in any of the Turkish subjects. Conclusion: Our result demonstrate for the first time that CHEK2 1100delC, IVS2+1G>A and I157T mutations have not been agenetic susceptibility factor for CRC in the Turkish population. Overall, our data suggest that genotyping of CHEK2 mutations in clinical settings in the Turkish population should not be recommended. However, independent studies are need to validate our findings in a larger series, as well as in patients of different ethnic origins. (C) 2012 Elsevier Ltd. All rights reserved.Cukurova University Research FundCukurova University [FEF2008D4]The authors thank all the subjects who participated in this study. We also thank Dr. Heli Nevanlinna, Dr. Cezary Cybulski, Dr. Natalia Bogdanova, Dr. Borge G. Nordestgaard for having kindly provided us with the 1100delC, I157T and IVS2+1G>A carrier DNAs used as a positive control. This work was supported by Cukurova University Research Fund FEF2008D4

CYP2C19 fonksiyonel polimorfizminin Helicobacter pylori eradikasyonu üzerine etkisi

Proton pompa inhibitörler, büyük ölçüde karaciğerde bulunan sitokrom P450 2C19 (CYP2C19) enzimi tarafından metabolize edilirler. Sitokrom P450 2C19 enziminin fonksiyonel polimorfizmi proton pompa inhibitörleri asit'baskılayıcı etkilerini değiştirebilir. Bu çalışmada, sitokrom P450 2C19 polimorfizminin proton pompa inhibitörler'temelli tedavilerde Helikobakter pilori eradikasyonu üzerinde etkisini araştırmayı amaçladık. Yöntem: Bu çalışmada, Helikobakter pilori'ye bağlı kronik gastrit tanısı olan 105 hastada sitokrom P450 2C19 genotipinin sıklığını ve bu genotipin Helikobakter pilori eradikasyon oranını belirledik. Üst gastrointestinal endoskopi ve gastrik biyopsi her hastada uygulandı. Helikobakter pilori tanısı histolojik olarak konuldu. Hastalara lansoprazol, amoksisilin ve klaritromisin günde 2 kez olmak üzere 14 gün süreyle uygulandı. Helikobakter pilori eradikasyonunu belirlemek üzere tedaviden bir ay sonra tüm hastalara 13C üre-solunum testi yapıldı. sitokrom P450 2C19 polimorfizmi polimeraz zincir reaksiyonu temelli-RFLP yöntemi ile saptandı. Bulgular: Sitokrom P450 2C19 polimorfizmleri 3 gruba ayrıldı; hızlı metabolize edici, orta derecede metabolize edici ve yavaş metabolize edici olmak üzere. Hastalarımız arasında, hızlı metabolize edici %72 oranında, orta derecede metabolize edici %23 oranında ve yavaş metabolize edici ise %5 oranında belirlendi. Helikobakter pilori eradikasyon oranı hızlı metabolize edici grupta %70 oranında, orta derecede metabolize edici grupta %92 ve yavaş metabolize edici grupta ise %80 oranında saptandı. Sonuç: Bulgularımız hızlı metabolize edici grupta Helikobakter pilori eradikasyon oranının düşük olduğunu doğrulamaktadır. Tedavi öncesi sitokrom P450 2C19 genotipinin belirlenmesi tedavi başarısının öngörülmesi açısından yararlı olur. Hızlı metabolize edici hastalarda Helikobakter pilori eradikasyon oranını yükseltmek amacıyla alternatif tedaviler denenebilir.Proton pump inhibitors are mainly metabolized by cytochrome P450 2C19 in the liver. Recently, some studies have shown that the acid�suppressing effect of proton pump inhibitors are influenced by a functional polymorphism of cytochrome P450 2C19. The aim of the present study was to investigate the effect of cytochrome P450 2C19 polymorphism on Helicobacter pylori eradication in patients who received proton pump inhibitors�based triple therapy. Methods: We determined the incidence of cytochrome P450 2C19 genotypes and the effect of cytochrome P450 2C19 genotypes on Helicobacter pylori eradication rates in 105 patients with Helicobacter pylori-positive chronic gastritis. Upper endoscopic procedure and gastric biopsies were performed in all patients. Helicobacter pylori was demonstrated histologically. Lansoprazole, amoxicillin and clarithromycin twice a day for 14 days were prescribed for those found to be infected with Helicobacter pylori. More than one month after the medication, a 13C urea breath test was conducted to examine the success or failure of the eradication treatment. Cytochrome P450 2C19 polymorphism was analyzed by the polymerase chain reaction�restriction fragment length polymorphism method. Results: The genotypes of cytochrome P450 2C19 were classified into the three groups, as rapid extensive metabolizer, intermediate metabolizer and poor metabolizer. In our patient population, the frequencies of rapid extensive metabolizer, intermediate metabolizer and poor metabolizer were 72%, 23% and 5%, respectively. The eradication rate was 70.0% for rapid extensive metabolizer, 92% for intermediate metabolizer and 80% for poor metabolizer. The eradication rate was highest in intermediate metabolizer patients. Conclusions: The present study confirmed the low eradication rate for rapid extensive metabolizer. Our findings provide evidence that the cytochrome P450 2C19 genotype is useful to predict the success of treatment. For the rapid extensive metabolizer group, alternative regimens can be tried to increase the Helicobacter pylori eradication rates

The role of Interleukin 28B gene polymorphism in Turkish patients with hepatocellular carcinoma

Background and aim. Multiple risk factors lead to hepatocellular carcinoma (HCC) including viral infections, mutation and single nucleotide polymorphisms (SNPs). Interleukin 28B (IL28B) gene rs12979860 polymorphism has been shown to be associated with HCC in the different populations, but its association with HCC has not been investigated in the Turkish population. We investigated whether the rs12979860 polymorphism of IL28B gene affects the risk of HCC.Material and method. We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 187 confirmed HCC patients and 208 healthy subjects (cancer and viral infection negative) in the Turkish population.Results. The allele and genotype analysis showed no significant differences between the risk of HCC and IL28B gene rs12979860 polymorphism (OR = 1.10; 95% 0.59-2.08 P = 0.76 for genotype). However, in the HBV-related HCC subgroup, the TT genotype increased a 1.46-fold the risk of developing HCC, but not statistically significant (OR = 1.46; 95% 0.71-2.97 P = 0.30). Furthermore, no significant differences were found between clinical findings, and sex in comparison with the IL28B genotypes in HCC group (P > 0.05).Conclusion. Our results suggest, for the first time, that no significant association were found between IL28B rs12979860 genotypes with the risk of developing HCC in Turkish patients. Further independent investigations are required to clarify the possible role of IL28B gene rs12979860 polymorphism on the risk of developing HCC in a larger series and also in patients of different ethnic origins

G-308A TNF-alpha polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case-control study

WOS: 000271784200016PubMed ID: 19683483Background: Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-alpha gene at position -308 promoter region is involved in the regulation of expression level and has been found to be associated with susceptibility to various types of cancer. Methods: To determine the association of the TNF-alpha gene G-308A polymorphism on the risk of hepatocellular carcinoma (HCC) in a Turkish population, a hospital-based case-control study was designed consisting of 110 diagnosis subjects with hepatocellular carcinoma and 110 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of this polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The distribution G-308A genotype was significantly associated with the risk of HCC (p < 0.001, odds ratio [OR] = 4.75, 95% confidence interval [CI] = 2.25-9.82 for -308 AA/GA genotypes versus GG genotype). Conclusion: We suggested that the presence of the high producer allele -308A in the TNF-alpha gene appears to be associated with an increased risk for the development of HCC in Turkish population. Published by Elsevier Ltd.Cukurova University Research FundCukurova University [TF2005BAP19]This study was funded by Cukurova University Research Fund TF2005BAP19