A functional polymorphism in pre-microRNA-196a-2 contributes to the susceptibility of hepatocellular carcinoma in a Turkish population: a case-control study.

MicroRNAs (miRNAs) are an abundant class of small nonprotein-coding RNAs with posttranscriptional regulatory functions as tumour suppressors and oncogenes. Aberrant expression and structural alteration of miRNAs are thought to participate in tumourigenesis and cancer development. It has been suggested that the presence of single-nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to the development of human cancers. Recent studies have indicated that the miR-196a-2 rs11614913 (C→T) polymorphism could alter mature miR-196a-2 expression and target mRNA binding. To determine the association of the miR-196a-2 rs11614913 polymorphism with the risk of hepatocellular carcinoma (HCC) development in a Turkish population, a hospital-based case-control study was designed consisting of 185 subjects with HCC and 185 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the miR-196a-2 rs11614913 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data shows that the CC genotype of the miR-196a-2 rs11614913 polymorphism is associated with increased risk of HCC development in this Turkish population (OR = 2.41, 95% CI: 1.30-4.50, P = 0.005). Furthermore, according to stratified analysis, a significant association was observed between the homozygote CC genotype and HCC risk in the subgroups of male gender (OR = 3.12, 95% CI: 1.53-6.34, P = 0.002) and patients with hepatitis B virus (HBV)-related HCC (OR = 2.88, 95% CI: 1.33-6.22, P = 0.007). Because our results suggest for the first time that the miR-196a-2 rs11614913 polymorphism may be a genetic susceptibility factor for HCC (especially in the male gender and HBV-infected patients) in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

Akkız H ，Bayram S ，Bekar A ，Akgöllü E ，Ulger Y ... -  《-》

No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: a case-control study.

MicroRNAs (miRNAs) are an abundant class of small non-protein coding RNAs with posttranscriptional regulatory functions as tumor suppressors and oncogenes. Aberrant expression and structural alteration of miRNAs are considered to participate in tumorigenesis and cancer development. It has been suggested that the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to the susceptibility of human cancers. A G/C polymorphism (rs2910164), which is located in the sequence of miR-146a precursor, results in a change from G:U to C:U in its stem region. To determine the association of the miR-146a rs2910164 polymorphism on the risk of hepatocellular carcinoma (HCC) development in Turkish population, a hospital-based case-control study was designed consisting of 222 subjects with HCC and 222 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of miR-146a rs2910164 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. No statistically significant differences were found in the allele or genotype distributions of the miR-146a rs2910164 polymorphism among HCC and cancer-free control subjects (p>0.05). Our results demonstrate that the miR-146a rs2910164 polymorphism has no major role in genetic susceptibility to hepatocellular carcinogenesis, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.

Akkız H ，Bayram S ，Bekar A ，Akgöllü E ，Usküdar O ，Sandıkçı M ... -  《-》

RASSF1A Ala133Ser polymorphism is associated with increased susceptibility to hepatocellular carcinoma in a Turkish population.

The tumor suppressor gene Ras association domain family 1 isoform A (RASSF1A) regulates cell cycle regulation, apoptosis and microtubule stability and is inactivated by promoter hypermethylation at a high frequency in hepatocellular carcinoma (HCC). A guanine (G)/thymine (T) common single nucleotide polymorphism (SNP) at first position of codon 133 in RASSF1A gene determines an alanine (Ala) to serine (Ser) (Ala133Ser) amino acidic substitution which may alter cancer risk by influencing the function of RASSF1A protein. To determine the association of the RASSF1A Ala133Ser polymorphism with the risk of HCC development in a Turkish population, a hospital-based case-control study was designed consisting of 236 subjects with HCC and 236 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the RASSF1A Ala133Ser polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Allele and genotype associations of RASSF1A Ala133Ser polymorphism with HCC susceptibility were observed in comparisons between the patient and control samples (P<0.001). Risk of HCC development in this Turkish population was significantly increased in carriers of the Ser133 variant allele of Ala133Ser polymorphism (Ala/Ser and Ser/Ser genotypes) when compared with homozygote Ala/Ala genotype (OR=5.47, 95% CI=3.63-8.25, P=0.001). Because our results suggest for the first time that the Ser133 allele of RASSF1A Ala133Ser polymorphism may be a genetic susceptibility factor for HCC in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

Bayram S 《-》

Genetic variation in the microRNA-499 gene and hepatocellular carcinoma risk in a Turkish population: lack of any association in a case-control study.

Akkiz H ，Bayram S ，Bekar A ，Akgöllü E ，Üsküdar O ... -  《-》

Association of a variant in MIR 196A2 with susceptibility to hepatocellular carcinoma in male Chinese patients with chronic hepatitis B virus infection.

MicroRNAs (miRNAs) are small noncoding RNAs with regulatory functions as tumor suppressors and oncogenes. Recent studies have implicated that the rs11614913 SNP in MIR196A2 was associated with susceptibility of lung cancer, congenital heart disease, breast cancer and shortened survival time of nonsmall cell lung cancer. To assess whether this polymorphism is associated with susceptibility to and clinicopathologic characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), a total of 560 patients with chronic HBV infection and 391 healthy volunteers were enrolled, and MIR196A2 polymorphism was genotyped by polymerase chain reaction-ligation detection reaction (PCR-LDR). In our study group, there was no significant association between MIR196A2 polymorphism and the risk of HBV-related HCC in all subjects, however, the risk of HCC was significantly higher with MIR196A2 rs11614913 CC genotype or C allele compared with those with the TT genotype or T allele in male patients. Furthermore, in a subsequent analysis of the association between this polymorphism and clinicopathologic characteristics, there was still no significant difference in both the distribution of genotype or allelic frequency. However, we observed that the T allele was significantly more frequent in male HCC patients with lymphatic metastasis. Our results suggested that MIR196A2 polymorphism was associated with susceptibility to HBV-related HCC in a male Chinese population.

Qi P ，Dou TH ，Geng L ，Zhou FG ，Gu X ，Wang H ，Gao CF ... -  《-》