• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5929-5934
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• 2013

Background: Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. ${\beta}3$ integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and ${\beta}3$ integrin gene polymorphisms. Materials and Methods: The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of ${\beta}3$ integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM-1 K469E, ICAM-1 R241G and ${\beta}3$ integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). Conclusions: This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3101-3109
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• 2015

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in amino acid synthesis and DNA function. Two common polymorphisms are reported, C677T and A1298C, that are implicated in a number of human diseases, including cancer. Objective: The association between MTHFR C677T and A1298C genotype and haplotype frequencies in risk for lung cancer (LC) was investigated in the Jordanian population. Materials and Methods: A total of 98 LC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 89 controls taken from the general population, employing the PCR-RFLP technique. Results: The frequency of the genotypes of MTHFR C677T among Jordanians was: CC, 59.6%, CT, 33%; and TT, 7.4% among LC cases and 49.4%, 40.2% and 10.3% among controls. No significant association was detected between genetic polymorphism at this site and LC. At MTHFR A12987C, the genotype distribution was AA, 29.5%; AC, 45.3%, and CC 25.3% among LC cases and 36.8%, 50.6% and 12.6% among controls. Carriers of the CC genotype were more likely to have LC (OR=2.5; 95%CI: 1.04-6; p=0.039) as compared to AA carriers. Smokers and males with the CC genotype were 9.9 and 6.7 times more likely to have LC, respectively ($OR_{smokers}=9.9$; 95%CI: 1.2-84.5, p=0.018; $OR_{men}=6.6$; 95%CI: 1.7-26.2, p=0.005). Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the CC haplotype (677C-1298C) between cases and controls. The CC haplotype was associated with an increased risk for lung cancer (OR=1.6; 95% CI: 1.03-2.4, p=0.037). Conclusions: The genetic polymorphism of MTHFR at 1298 and the CC haplotype (risk is apparently lower with the C allele at position 677) may modulate the risk for LC development among the Jordanian population. Risk associated with the 1298C allele is increased in smokers and in males. The results indicate that a critical gene involved in folate metabolism plays a modifying role in lung cancer risk, at least in the Jordanian population.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4215-4218
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• 2015

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.717-723
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• 2014

Background: This study was carried out to investigate the interaction of p53 codon 72 polymorphism, dietary and tobacco habits with reference to risk of stomach cancer in Mizoram, India. A total of 105 histologically confirmed stomach cancer cases and 210 age, sex and ethnicity matched healthy population controls were included in this study. Materials and Methods: The p53 codon 72 polymorphism was detected by PCR-RFLP and sequencing. H. pylori infection status was determined by ELISA. Information on various dietary and tobacco related habits was recorded with a standard questionnaire. Results: This study revealed that overall, the Pro/Pro genotype was significantly associated with a higher risk of stomach cancer (OR, 2.54; 95%CI, 1.01-6.40) as compared to the Arg/Arg genotype. In gender stratified analysis, the Pro/Pro genotype showed higher risk (OR, 7.50; 95%CI, 1.20-47.0) than the Arg/Arg genotype among females. Similarly, the Pro/Pro genotype demonstrated higher risk of stomach cancer (OR, 6.30; 95%CI, 1.41-28.2) among older people (>60 years). However, no such associations were observed in males and in individuals <60 years of age. Smoke dried fish and preserved meat (smoke dried/sun dried) consumers were at increased risk of stomach cancer (OR, 4.85; 95%CI, 1.91-12.3 and OR, 4.22; 95%CI, 1.46-12.2 respectively) as compared to non-consumers. Significant gene-environment interactions exist in terms of p53 codon 72 polymorphism and stomach cancer in Mizoram. Tobacco smokers with Pro/Pro and Arg/Pro genotypes were at higher risk of stomach cancer (OR, 16.2; 95%CI, 1.72-153.4 and OR, 9.45; 95%CI, 1.09-81.7 respectively) than the non-smokers Arg/Arg genotype carriers. The combination of tuibur user and Arg/Pro genotype also demonstrated an elevated risk association (OR, 4.76; 95%CI, 1.40-16.21). Conclusions: In conclusion, this study revealed that p53 codon 72 polymorphism and dietary and tobacco habit interactions influence stomach cancer development in Mizoram, India.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.2
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• pp.280-285
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• 2006

The current study was conducted to investigate the relationship between stress related gene and meat quality in pigs. A total number of 212 three-way cross bred (Landrace-$Yorkshire{\times}Duroc$) and 38 Duroc were sampled from the Korean pig industry to determine genotype frequency of porcine stress syndrome (PSS) and heat shock protein 70 kDa (HSP70) genes and their relationship with carcass traits and longissimus meat quality. Screen of HSP70 was performed by the single strand conformation polymorphism (SSCP) technique. Based on the analysis of restriction fragment length polymorphism (RFLP) in ryanodine receptor 1 (RYR1) gene, genetic disorder of PSS was related to a mutation at $18,168^{th}$ (C to T) of exon 17. There was no significant difference in ultimate meat pH and backfat thickness between HSP70 K1-AA type and -BB type in pure Duroc breed. In Landrace-$Yorkshire{\times}Duroc$ (L-$Y{\times}D$) cross bred pig, our results indicated that HSP70 derivate type in Duroc had a limited effect on backfat thickness, but L-$Y{\times}D$ type had a noticeable linkage with HSP70 K1-AA and K3-AB. This tendency was also observed in hot carcass weight where HSP70 K1-AA and K3-AB resulted in heavier weight with 86.3 kg compared to HSP70 K1-AB and K3-BB of 74.3 kg. Results imply that stress related HSP70 genotype has a potential association with backfat thickness and carcass weight.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.619-624
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• 2013

Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

• Preventive Nutrition and Food Science
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• v.9 no.1
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• pp.71-78
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• 2004

Adrenergic receptors play a major role in thermogenesis and lipolysis in brown and visceral adipose tissues, and have been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of $\beta$2-adrenergic receptor ($\beta$2AR) and $\beta$3-adrenergic receptor ($\beta$3AR) genotypes on hyperglycemia and obesity in the Korean population. A representative sample consisting of 530 Korean men and women were measured for height, weight, BMI, WHR, obesity index and body composition. The genotypes of $\beta$2AR polymorphism in codon 27 and $\beta$3AR polymorphism in codon 64 were analyzed by the PCR RFLP method. Serum concentrations of fasting glucose, total cholesterol, HDL cholesterol and triglyceride were determined. The frequencies of $\beta$2AR and $\beta$3AR genotype were: both wild type, 62.5% ; only $\beta$2AR variant type, 12.8% ; only $\beta$3AR variant type, 18.8% ; and both variant type, 5.8% ; the frequency of E and R alleles were 0.098 and 0.137, respectively. Among the physiological parameters, fasting glucose level was significantly higher in subjects with both variant type compared with the three other types (p <0.05), Subjects with both variant type had 12%, 12% and 9.3% increases in serum glucose levels compared with wild type, only $\beta$2AR variant type, and only $\beta$3AR variant type, respectively. When logistic regression analysis was conducted to estimate the risk for hyperglycemia, the subjects were selected for fasting blood glucose concentrations of more than 6.105 m㏖/L (110 mg/dL), and the odds ratios were 1.215 (p=0.636) for only $\beta$2AR variant type,1.659 (p=0.089) for only $\beta$3AR variant type, and 3.078 (p=0.011) for both variant type. These results suggest that the interaction of $\beta$2AR and $\beta$3AR variant genotypes has a strong association with increased glucose levels, and might be a significant risk factor for hyperglycemia among Korean subjects.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.318-322
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• 2008

Obesity is an increasing worldwide health problem that is strongly related to the imbalance of food intake and energy metabolism. It was well-known that several substances in the hypothalamus regulate food intake and energy metabolism. We planned an integrative study to elucidate the mechanism of the development of obesity. Firstly, to find candidate genes with the marvelous effect, the different expression in the hypothalamus between ob/ob and 48-h fasting mice was investigated by using DNA microarray technology. As a result, we found 3 genes [peroxisome proliferator activated receptor, gamma, coactivator 1 alpha (Ppargc1a), calmodulin 1 (Calm1), and complexin 2 (Cplx2)] showing the different hypothalamic expression between ob/ob and 48-h fasting mice. Secondly, a genetic approach on PPARGC1A gene was performed, because PPARGC1A acts as a transcriptional coactivator and a metabolic regulator. Two hundred forty three obese female patients with body mass index (BMI)${\geq}$25 and 285 control female subjects with BMI 18 to<23 were recruited according to the Classification of Korean Society for the Study of Obesity. Among the coding single nucleotide polymorphisms (cSNPs) of PPARGC1A, 2 missense SNPs (rs8192678, Gly482Ser; rs3736265, Thr612Met) and 1 synonymous SNP (rs3755863, Thr528Thr) were selected, and analyzed by PCR-RFLP and pyrosequencing. For the analysis of genetic data, chi-square ($X^2$) test and EH program were used. The rs8192678 was significantly associated with obese women (P<0.0006; odds ratio, 1.5327; 95% confidence interval, 1.2006-1.9568). Haplotypes also showed significant association with obese women ($X^2$=33.28, P<0.0008). These results suggest that PPARGC1A might be related to the development of obesity.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.767-775
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• 2008

Uncoupling protein-1 (UCP-1) plays a major role in thermogenesis at brown adipose tissues and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of A-3826G polymorphism in 117 Korean prepubertal children aged 8-11 years olds. Anthropometry by bioelectrical impedance analysis method, plasma lipid profiles by auto-biochemical analyzer and UCP-1 genotyping by PCR-RFLP were done. The frequencies of UCP-1 genotypes were AA; 17.7%, AG; 57.8%, GG; 26.6%. The frequencies of each G allele (55.5%) was similar to Japanese's (49%) and higher than Caucacian's (25%). No correlation UCP-1 polymorphism and BMI (kg/$m^2$) or the degree of obesity described by the relative percentiles of the standard weight according to height in prepubertal children. However, plasma total- and LDL-cholesterol were significantly increased in G allele when sex, age and weight were adjusted. Our results suggested that G allele of UCP-1 gene was stronger risk factors in hyperLDLcholesterolemia than A allele. This impact might be progressed as the precaution against the revalence of obesity based-metabolic disease.

• Journal of Animal Science and Technology
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• v.51 no.4
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• pp.283-288
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• 2009

This study was carried out to compare Msp I polymorphisms in the 3rd intron of porcine gene encoding the pituitary-1 transcription factor (POU1F1) from 286 pigs (Landrace $\times$ Yorkshire $\times$ Duroc, LYD) and to determine the associations between its genotypes and carcass traits by using the PCR-RFLP technique. The frequency of the single nucleotide polymorphism (SNP) genotype DD (84.33%) was very higher than that of CC genotype (0.75%). Allelic frequencies for C and D were 0.082 and 0.918, respectively. Each population followed the Hardy-Weinberg equilibrium. Meat colours of Hunter $L^*$ values and visual colour according to two genotypes were all significantly different. However, no significant difference in crossbred (LYD) was found between CD and DD genotypes for other traits. Therefore, this suggests that POU1F1 may be a major gene or marker for carcass traits.