• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.4
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• pp.373-382
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• 2000

Individual genetic susceptibilities to cancers may result from several factors including differences in xenobiotics metabolism to chemical carcinogens, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. Among them, genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. They have two main types of enzymes: the phase I cytochrome P-450 mediating enzymes (CYPs) and phase II conjugating enzymes. The purpose of this study is to determine the frequencies of genotypes of phase I (CYP1A1 and CYP2E1) and phase II (NAT2) metabolizing enzymes in healthy control and head and neck cancer patients of Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer in Korean. The author has analyzed 132 head and neck cancer patients and 113 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results were as following; 1. The frequencies of genotypes of CYP1A1, CYP2E1 and NAT2 in healthy control were as following; CYP1A1 exon 7 polymorphism; Ile/Ile: Ile/Val: Val/Val = 59.3%: 36.3%: 4.4% CYP2E1 Pst I polymorphism, C1/C1: C1/C2: C2/C2 = 61.1%: 32.1%: 6.2% NAT2 polymorphism; F/F: F/S: S/S = 43.4%: 48.7%: 8.0% 2. In analysis of phase I enzyme, Val/Val genotype in CYP1A1 exon 7 polymorphism and C2/C2 genotype in CYP2E1 Pst I polymorphism were associated with relative high risks to head and neck cancers (Odds' ratio: 2.09 and 1.37, respectively). 3. Among the genotypes of NAT2 enzyme polymorphism, S/S genotype of NAT2 enzyme had 1.03 times of relative risk to head and neck cancers. 4. In combined genotyping of CYP1A1, CYP2E1, and NAT2 enzymes polymorphisms, the patients with Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator had higher relative risks than the patients with each baseline of combined genotypes (Odds' ratio: 2.82, 1.98 and 2.1, respectively). These results suggest the combined genotypes of Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator were more susceptible to head and neck cancers in Korean. And genotyping of metabolizing enzymes could be useful for predicting individual susceptibility to head and neck cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8413-8422
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• 2014

Background: To investigate the relationship of five TP53 polymorphisms (p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a) with the esophageal cancer (EC) risk in North Indians. Materials and Methods: Genotyping of p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a polymorphisms of TP53 in 136 sporadic EC patients and 136 controls using polymerase chain reaction and PCR-RFLP. Results: The frequencies of genotype RR, RP and PP of p.R72P polymorphism were 16.91 vs 26.47%, 58.82 vs 49.27% and 24.27 vs 24.27% among patients and controls respectively. We observed significantly increased frequency of RP genotype in cases as compared to controls (OR=1.87, 95% CI, 1.01-3.46, p=0.05). The frequencies of genotype A1A1, A1A2 and A2A2 of PIN3 ins16bp polymorphism were 69.12 vs 70.59%, 27.20 vs 25% and 3.68 vs 4.41% among patients and controls. There was no significant difference among genotype and allele distribution between patients and controls. The frequencies of genotype GG, GA and AA of r.13494g>a polymorphism were 62.50 vs 64.70%, 34.56 vs 30.15% and 2.94 vs 5.15% among patients and controls respectively. No significant difference between genotype and allele frequency was observed in the patients and controls. For p.P47S and p.R213R polymorphisms, all the cases and controls had homozygous wild type genotype. The RP-A1A1-GG genotype combination shows significant risk for EC (OR=2.01, 95%CI: 1.01-3.99, p=0.05). Conclusions: Among the five TP53 polymorphisms investigated, only p.R72P polymorphism may contributes to EC susceptibility.

• Nutritional Sciences
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• v.6 no.4
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• pp.239-245
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• 2003

The $\beta$3-adrenergic receptor ($\beta$3AR) plays a major role in thermogenesis and lipolysis in brown and visceral adipose tissue, and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of $\beta$3AR gene polymorphism on the risk of hyperglycemia in 980 Korean women who attended a weight loss program in a local clinic. Each subject s height, weight, BMI, WHR, obesity index and body composition were measured. The genotype of the $\beta$3AR gene in codon 64 was analyzed by the PCR RFLP method. Serum concentrations of fasting glucose, of total and HDL cholesterol, and of TG were determined. Genotype distributions were as follows : 67% WW type, 31% WR type, and 2% RR type. Among the many measured parameters, fasting glucose levels were significantly higher in the WR/RR type compared with the WW type (p=0.0ll). When the subjects were divided into two groups by a fasting blood glucose level higher or lower than 6.105mmol/L (110mg/dl), the frequency of hyperglycemia showed a significant difference in relation to $\beta$3AR genotype as measured by $\X^2$-analysis (p=0.014); the frequency of hyperglycemia was significantly higher (at 24.8%) in WR/RR type subjects, compared to 18.2% in WW type subjects. When all of the measured parameters were included in stepwise logistic regression analyses to find the risk factors for hyperglycemia, the odds ratios for hyperglycemia were 1.573 (p=0.0ll) for the WR/RR type of the $\beta$3AR gene, 1.053 (p=0.001) for TG, 1.044 (p=0.037) for BMI, and 1.026 for age (p=0.031). These data suggest that the WR/RR genotype of the $\beta$3AR has a very strong association with increased blood glucose level and might be a significant risk factor for hyperglycemia among Korean women.

• International Journal of Industrial Entomology and Biomaterials
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• v.18 no.1
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• pp.18-27
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• 2009

B. thuringiensis strain LY-99 belonging to subsp. alesti (H3a3c), was isolated from Chinese tobacco warehouse and showed significantly high toxicity to Plutella xylostella. For the identification of the cry1-type genes from B. thuringiensis LY-99, an extended multiplex PCRrestriction fragment length polymorphism (PCRRFLP) method was established by using two pairs of universal primers based on the conserved regions of the cry1-type genes to amplify around 2.4 kb cry1-type gene fragments. Then the DNA fragment was cloned into pGEM-T Easy vector and digested with EcoRI and EcoRV enzymes. Through this method, a known cry1-type gene was successfully identified from the reference strain, B. thuringiensis subsp. alesti. In addition, the RFLP patterns revealed that B. thuringiensis LY-99 included a novel cry1A-type gene in addition to cry1Aa, cry1Ac, cry1Be and cry1Ea genes. The novel cry1A-type gene was designated cry1Ah2 (Genbank accession No DQ269474). An inverse PCR method was used to amplify the flank regions of cry1Ah2 gene. Finally, 3143 bp HindIII fragment from B. thuringiensis LY-99 plasmid DNA including 5' region and partial ORF was amplified, and sequence analysis revealed that cry1Ah2 gene from LY-99 showed 89.31% of maximum sequence similarity with cry1Ac1 crystal protein gene. In addition, the deduced amino acid sequence of Cry1Ah2 protein shared 87.80% of maximum identity with that of Cry1Ac2. This protein therefore belongs to a new class of B. thuringiensis crystal proteins.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2747-2751
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• 2014

Background: DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population. Materials and Methods: We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequenci es, haplotype and linkage disequilibrium were determined using SNPstat software. Results: For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotypte association with NPC gave a p-value of 0.054. Conclusions: Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7467-7472
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• 2013

Background: Polymorphisms of genes encoding cytokines could be potential biomarkers to predict risk of gastric cancer (GC). Here, we investigated the association between the IL-6 -6331 (T/C, rs10499563) polymorphism in its promoter region and GC risk. Methods: In this case-control study of 215 GC cases and 518 non-cancer controls, the IL-6 -6331 (T/C, rs10499563) polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Individuals with the TC or CC genotype were associated with a significantly decreased risk of GC (OR=0.710, 95%CI: 0.504-0.999, P=0.049) compared with TT wild-type carriers. Ther C allele was also associated with significantly decreased risk of GC (OR=0.715, 95%CI: 0.536-0.954, P=0.023) compared with the T allele. In the stratification analysis, TC or CC genotypes were associated with significantly decreased GC risk in subgroups of males, people older than 60, and H. pylori-positive cases. However, no significant interaction was observed for TC or CC genotypes with H. pylori infection. On stratification with the Lauren classification, TC or CC genotypes were associated with significantly decreased risk of diffuse-type GC (OR=0.497, 95%CI: 0.266-0.925, P=0.027), also in subgroups of males, people older than 60, and H. pylori-positive cases. Conclusions: The IL-6 -6331 (T/C, rs10499563) polymorphism is associated with genetic susceptibility of GC and may have the potential to predict GC risk.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.242-247
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• 2003

Background: Psoriasis is an inflammatory skin disorder that is characterized by a marked proliferation of keratinocytes, vascular dilation and leukocyte infiltration. Cytokines play important roles in the pathogenesis of inflammatory disorders. An overexpression of proinflammatory cytokines was characterized in psoriasis plaque. Among these cytokines, IL-$1{\beta}$ is major pro-inflammatory cytokine synthesized during the infection and inflammatory process. The IL-1 receptor antagonist (IL-1Ra) competes for the same IL-1 receptor for $IL-1{\alpha}$ and $-1{\beta}$, which prevents activation of the target cells. Three single nucleotide polymorphisms (SNPs) in the IL-$1{\beta}$ gene have been reported at position -31, -511 and +3954. Within the IL-1Ra gene (IL-1RN), there is a variable number of tandem repeats (VNTR) of an 86 bp length in intron 2. These polymorphisms related to cytokine production and associated with various diseases. Methods: We investigated the polymorphisms of IL-1B (promoter -511 and +3954) and IL-1RN on 114 psoriasis patients and 311 healthy normal controls in Korean. We performed PCR-RFLP on single nucleotide polymorphisms (SNPs) of IL-1B (promoter -511 and +3954) and fragment analysis on IL-1RN 86 bp VNTR polymorphism. Results: The frequency of IL-1B $-511^*1$ allele (patients vs. controls; 50.0% vs. 42.3%, RR=1.4) was significantly increased and IL-1B $-511^*2$ allele (patients vs. controls; 50.0% vs. 57.7%, RR=0.7) decreased in psoriasis patients compared to normal controls. We also analyzed the IL-1B -511 polymorphism according to patients' characters (age of onset, sex and family history). The IL-1B -511 alleles were significantly associated in patients with male and family history than health normal controls. There were no significant associations of IL-1B +3954 and IL-1RN polymorphisms with psoriasis patients. Conclusion: These results suggest that the polymorphism of IL-1B -511 could be genetic susceptibility to psoriasis in Koreans.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.134-140
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• 2006

Because shipyard workers are involved with various manufacturing process in shipyard industry, and they are exposed to many kinds of hazardous materials. Especially, painting workers were exposed polycyclic aromatic hydrocarbons (PAH). This study was conducted to assess the exposure status of PAH based on job-exposure matrix. We investigated the effect of genetic polymorphism of xenobiotic metabolism enzymes involved in PAH metabolism on levels of urinary metabolite. A total of 93 shipbuilding workers were recruited in this study. Questionnaire variables were age, sex, use of personal protective equipment, smoking, drinking, and work duration. The urinary metabolite was collected in the afternoon and corrected by urinary creatinine concentration. The genotypes of CYP1A1, CYP2E1, GSTM1, GSTT1 and UGT1A6 were investigated by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods with DNA extracted from venous blood. Urinary 1-OHP levels were significantly higher in direct exposured group (spray and touch-up) than indirect exposed group. Urinary 1-OHP, concentration of the high exposure with wild type of UGT1A6 was significantlyhigher than that of the high exposure with other UGT1A6 genotype. In multiple regression analysis of urinary 1-OHP, the regression coefficient of job grade was statistically significant (p<0.05) and UGT1A6 was not significant but a trend (p<0.1). The grade of exposure affected urinary PAH concentration was statistically significant. But genetic polymorphism of xenobiotics metabolism enzymes was not statistically significant. Further investigation of genetic polymorphism with large sample size is needed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4017-4023
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• 2012

Background and Aim: Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) are known to be associated with predisposition for certain cancers. This study aimed to evaluate the effects of lifestyle factors, family history and genetic polymorphisms in MTHFR C677T and A1298C on rectal cancer risk and possible interactions with lifestyle factors in Northeast Thailand. Methods: A hospital-based case-control study was conducted during 2002-2006 with recruitment of 112 rectal cancer cases and 242 non-rectal cancer patient controls. Information was collected using a structured-questionnaire. Blood samples were obtained for assay of MTHFR C677T and A1298C genotypes by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) techniques. Associations between lifestyle factors, family history and genetic polymorphisms v.s. rectal cancer risk were assessed using logistic regression analysis. Results: Subjects with frequent and occasional constipation had a higher risk ($OR_{adj.}$=14.64; 95%CI=4.28-50.04 and $OR_{adj.}$=2.15; 95%CI=1.14-4.06), along with those who reported ever having hemorrhoids ($OR_{adj.}$=2.82; 95%CI=1.36-5.84) or a family history of cancer ($OR_{adj.}$=1.90; 95%CI=1.06-3.39). Consumption of a high level of pork was also associated with risk ($OR_{adj.}$=1.82; 95%CI=1.05-3.15). Interactions were not observed between MTHFR and other risk factors. Conclusions: This study suggested that the risk factors for rectal cancer in the Thai population are bowel habits, having had hemorrhoids, a family history of cancer and pork consumption.

• Korean Journal of Agricultural Science
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• v.38 no.3
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• pp.453-458
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• 2011

The MC1R (Melanocortin 1 receptor) gene has been known as a causative gene of the coat colors in mammals and responsible for the E (Extension) locus which has three alleles ($E^D$, $E^+$, e) that determines coat colors. The dominant allele $E^D$ produces black or brown colors due to the missense mutation and the recessive e allele has frameshift mutation which shows red or yellow coat colors. Whereas the wild type $E^+$ produces variety of colors due to the interaction with A (Agouti) locus. In this study, PCR-RFLP was performed using two restriction enzymes (BsrF I and MspA1 I) in order to obtain MC1R genotypes in Korean brindle cattle and black cattle. The results showed that all of the animals have the $E^+$ alleles, indicating the $E^+$ allele might related with black coat colors. Later on, the experiments expanded to the 260 Korean candidate bulls whether these animals have the same $E^+$ allele. Among 260 samples investigated, 5% (13/260) of the animals had $E^+$e genotypes, indicating the $E^+$ allele is also present in the candidate bulls in a low frequency. Even though we expected that A locus also affect the black coat color in cattle, all the black coat color animals (brindle and black) have $E^+$ alleles in this study. Therefore, the genotyping of the MC1R gene in candidate bulls will recommended be applied for eliminating of black coat colors in Hanwoo population, if the farmers need to have the brown coat colors only.