• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.1047-1055
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• 2014

Background: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. Methodology/Principal Findings: PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-$196a2^*T$ variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. Conclusions: These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3165-3172
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• 2012

Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.

• Journal of the Korean Data and Information Science Society
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• v.25 no.5
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• pp.1057-1067
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• 2014

Many genetic variants have been identified to be associated with complex diseases such as hypertension, diabetes and cancers throughout genome-wide association studies (GWAS). However, there still exist a serious missing heritability problem since the proportion explained by genetic variants from GWAS is very weak less than 10~15%. Gene-gene interaction study may be helpful to explain the missing heritability because most of complex disease mechanisms are involved with more than one single SNP, which include multiple SNPs or gene-gene interactions. This paper focuses on gene-gene interactions with the survival phenotype by extending the multifactor dimensionality reduction (MDR) method to the accelerated failure time (AFT) model. The standardized residual from AFT model is used as a residual score for classifying multiple geno-types into high and low risk groups and algorithm of MDR is implemented. We call this method AFT-MDR and compares the power of AFT-MDR with those of Surv-MDR and Cox-MDR in simulation studies. Also a real data for leukemia Korean patients is analyzed. It was found that the power of AFT-MDR is greater than that of Surv-MDR and is comparable with that of Cox-MDR, but is very sensitive to the censoring fraction.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2597-2604
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• 2012

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P < 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P < 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P < 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.

• Korean Journal of Biological Psychiatry
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• v.19 no.3
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• pp.128-133
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• 2012

Objectives : Located on chromosome 10q22-q23, the human neuregulin 3 (NRG3) is suggested as a strong positional and functional candidate gene involved in the pathogenesis of schizophrenia. Several case-control studies examining the association between polymorphisms on NRG3 gene with schizophrenia and/or its traits (such as delusion) have been reported recently in cohorts of Han Chinese, Ashkenazi Jews, Australians, white Americans of Western European ancestry and Koreans. Thus, this study aimed to investigate the association of one SNP in exon 9 (rs2295933) of NRG3 gene with the risk of schizophrenia in a Korean population. Methods : Using TaqMan assay, rs2295933 in the exon 9 of NRG3 was genotyped in 435 patients with schizophrenia as cases and 393 unrelated healthy individuals as controls. Differences in frequency distributions were analyzed using logistic regression models following various modes of genetic inheritance and controlling for age and sex as covariates. Results : Subsequent analysis revealed that the frequency distribution of rs2295933 of NRG3 was not different between schizophrenia patients and healthy controls of Korean ethnicity. Conclusions : This study does not support the role of NRG3 in schizophrenia in a Korean population.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.303-311
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• 2002

This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

• Anxiety and mood
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• v.4 no.2
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• pp.142-147
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• 2008

Objective : Evidence from recent studies supports the role of genetic factors in the development of Posttraumatic Stress Disorder (PTSD). The primary aim of this study is to investigate the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. The second aim is to examine the association between the DRD2 TaqI A polymorphism and clinical symptoms in patients with PTSD. Methods : We recruited 189 Vietnam veterans for participation in this study, among whom 99 were PTSD patients and 90 were control subjects. The presence of the DRD2 TaqI A polymorphism was determined by polymerase chain reaction (PCR). Several standardized research scales were used in the clinical assessment of PTSD, including the Combat Exposure Scale (CES), Clinician Administered PTSD Scale (CAPS), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI). Results : There was no significant difference in the distribution of the DRD2 genotype, frequency and prevalence of the A1 allele, or the frequency of heterozygotes between the patients with PTSD and the controls. In the PTSD group, the patients with the A1 allele (A1A1, A1A2) scored higher on the CAPS-total (p=0.044), CAPS-avoidance symptoms (p=0.016) and BDI (p=0.024) than those without the A1 allele (A2A2). Conclusion : We could not find an association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. However, the A1 allele of DRD2 seemsto influence avoidance symptoms in patients with PTSD.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2019-2025
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• 2016

Hepatocellular carcinoma (HCC) is major health problem with high mortality rates, especially in patients with hepatitis B virus (HBV) infection. Telomerase function is one of common mechanisms affecting genome stability and cancer development. Recent studies demonstrated that genetic polymorphisms of telomerase associated genes such as telomerase associated protein 1 (TEP1) rs1713449 and PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1) rs1469557 may be associated with risk of HCC and other cancers. In this study, 325 patients with HCC and 539 non-HCC groups [193 healthy controls, 80 patients with HBV-related liver cirrhosis (LC) and 266 patients with HBV-related chronic hepatitis (CH)] were enrolled to explore genetic polymorphisms of both SNPs using the allelic discrimination method based on MGB probe TaqMan real time PCR. We demonstrated that all genotypes of both genes were in Hardy-Wienberg equilibrium (P>0.05). Moreover, there was no significant association between rs1713449 genotypes and HCC risk, HCC progression and overall survival (P>0.05). Interestingly, we observed positive association of rs1469557 with risk of HCC when compared with the LC group under dominant (CC versus CT+TT, OR=1.89, 95% CI= 1.06-3.40, P=0.031) and allelic (C versus T alleles, OR=1.75, 95% CI=1.04-2.94, P=0.033) models, respectively. Moreover, overall survival of HCC patients with CC genotype of rs1469557 was significantly higher than non-CC genotype (Log-rank P=0.015). These findings suggest that PINX1 rs1469557 but not TEP1 rs1469557 might play a role in HCC progression in Thai patients with LC and be used as the prognosis marker to predict overall survival in HCC patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4617-4622
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• 2014

Background: Several studies have previously focused on associations between the (GT)n repeat polymorphism of the heme oxygenase-1 (HO-1) gene promoter region and risk of cancers, but results are complex. We conducted the present meta-analysis to integrate relevant findings and evaluate the association between HO-1(GT)n repeat polymorphism and cancer susceptibility. Materials and Methods: Published literature was retrieved from the PubMed/MEDLINE, EMBASE and ISI Web of Science databases before November 2013. For all alleles and genogypes, odds ratios were pooled to assess the strength of the associations using either fixed-effects or random-effects models according to heterogeneity. Subgroup analysis was conducted according to ethnicity and histopathology. Results: A total of 10 studies involving 2,367 cases and 2,870 controls were identified. The results showed there was no association between HO-1 (GT)n repeat polymorphism and the cancer risk both at the allelic and genotypic level. However, in the stratified analysis, we observed an increased risk of squamous cell carcinoma in persons carrying the LL genotype and the LL+LS genotype as compared with those carrying the SS genotype. When the LS and SS genotypes were combined, the odds ratio for squamous cell carcinoma in LL-genotype carriers, were also significantly increased. No publication bias was observed. Conclusions: The LL genotype and L-allele carrying genotypes (LL+LS) of HO-1 (GT)n repeat polymorphism are potential genetic factors for developing squamous cell carcinoma. More large and well-designed studies are required for further validations.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4107-4111
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• 2016

Background: Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is five to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population. Materials and Methods: In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays. Results: The results indicated significantly higher risk with PARP1 rs1136410 minor allele "C" (OR=1.909; p=0.02942; CI, 1.060-3.439). SNP rs1136410 also showed significantly increased risk in patients with smoking habit at C/C genotype and at minor allele C. Conclusions: The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with a greater number of samples are needed to verify these findings.