CD44 Gene Polymorphisms on Hepatocellular Carcinoma Susceptibility and Clinicopathologic Features

Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths in Taiwan. CD44, one of the well-known tumor markers, plays an essential role in tumor cell differentiation, invasion, and metastasis. We investigated the CD44 single-nucleotide polymorphisms (SNPs) with environmental risk factors related to HCC susceptibility and clinicopathological characteristics. Six SNPs of CD44 were analyzed using a real-time polymerase chain reaction (PCR) in 203 patients with HCC and in 561 cancer-free controls. We determined that the individuals carrying at least one G allele at CD44 rs187115 has higher risk of developing HCC than did wild-type (AA) carriers. We further observed that the CD44 rs187115 polymorphisms with at least one G allele had a higher frequency of distribution in nonsmoking stage III/IV HCC patients, compared with wild-type carriers. Our results suggested that patients with CD44 rs187115 variant genotypes (AG+GG) were associated with a higher risk of HCC development and that these patients might possess chemoresistance, causing more likely progression to late-stage HCC than wild-type carriers without the overexpression of CD44 induced by heavy smoking. CD44 rs187115 might be involved in CD44 isoform expression of p53 stress response in HCC and provide a marker for predicting worst-case prognosis of HCC

Effects of EZH2 polymorphisms on susceptibility to and pathological development of hepatocellular carcinoma.

The enhancer of zeste 2 (EZH2) gene encodes the histone methyltransferase that is the catalytic component of the polycomb repressive complex-2, which initiates epigenetic silencing of genes. The expression level of EZH2 in hepatocellular carcinoma (HCC) is highly correlated with tumor progression; however, it has not been determined if specific EZH2 genetic variants are associated with the risk of HCC. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with HCC susceptibility and its clinicopathologic characteristics.A total of 220 HCC patients and 552 cancer-free controls were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, the individuals carrying at least one C allele at EZH2 rs6950683 and rs3757441 had a 0.611-fold and a 0.660-fold lower risk of developing HCC than did wild-type (TT) carriers, respectively. The CCCA or CCTA haplotype among the four EZH2 sites (rs6950683, rs2302427, rs3757441, and rs41277434), respectively, was also associated with a reduced risk of HCC. Furthermore, HCC patients who carried at least one C allele at rs6950683 or rs3757441 had a higher lymph-node-metastasis risk but a lower liver-cirrhosis risk than did patients carrying the wild-type allele.The rs6950683 and rs3757441 polymorphic genotypes of EZH2 might contribute to the prediction of susceptibility to and pathological development of HCC. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of HCC in Taiwan

Mucosal patterns of Helicobacter pylori-related gastritis without atrophy in the gastric corpus using standard endoscopy

AIM: To identify the mucosal patterns of Helicobacter pylori (H. pylori)-related gastritis in the gastric corpus using standard endoscopy and to evaluate their reproducibility

Demographic characteristics of controls and patients with HCC.

*<p>, considered statistically significant.</p><p>S.D., standard deviation.</p

Distribution frequency of <i>EZH2</i> haplotype in control and HCC patients.

*<p>, considered statistically significant.</p

Associations of clinical status and <i>EZH2</i> rs3757441 genotypic frequencies in 220 HCC patients.

<p>The AORs with their 95% CI were estimated by multiple logistic regression models, after controlling for age, gender, tobacco use and alcohol consumption.</p><p>>T2: multiple tumor more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)</p>*<p>, considered statistically significant.</p

Association of <i>EZH2</i> genotypic frequencies with HCC blood biochemistry results.

<p>Mann-Whitney U test was used between two groups.</p><p>Values presented are the mean ± standard error.</p

Associations of clinical status and <i>EZH2</i> rs6950683 genotypic frequencies in 220 HCC patients.

<p>AORs with their 95% CIs were estimated by multiple logistic regression models after controlling for age, gender, tobacco use and alcohol consumption.</p><p>>T2: multiple tumor >5 cm in the greatest dimension or tumor involving a major branch of the portal or hepatic vein(s)</p>*<p>, considered statistically significant.</p