• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.189-193
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• 2013

Many epidemiological studies in Asian populations have investigated associations between the Arg399Gln gene polymorphism of X-ray repair cross complementing gene 1 (XRCC1) and risk of cervical carcinoma, but no conclusions have been available because of controversial results. Therefore a meta-analysis was conducted for clarification. Relevant studies were identified by searching the Pubmed, Embase, the Web of Science, Cochrane Collaboration's database, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and China Biological Medicinse (CBM) until September, 2012. A total of eight studies were included in the present meta-analysis, which described 1,759 cervical carcinoma cases and 2,497 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) as effect size were calculated by fixed-effect or random-effect models. The overall results indicated that the XRCC1-399G/A polymorphism was marginally associated with cervical carcinoma in Asians: OR (95%CI): 1.16 (1.07, 1.26) in the G/A vs G/G inheritance model, 1.24 (0.87, 1.76)in A/A vs G/G inheritance model, 1.13 (1.01, 1.27) in the dominant inheritance model and 1.18 (0.94, 1.47) in the recessive inheritance model. Subgroup analyses on sample size showed no significant correlation in the small-sample size group but the large-sample size group was consistent with the outcomes of overall meta-analysis. In the subgroup analysis by regions, we only found significant association under the G/A vs G/G inheritance model in the Chinese population. For the non-Chinese populations, no correlation was detected in any genetic inheritance model. In the Asian populations, XRCC1-399G/A gene polymorphism was implied to be associated with cervical carcinoma.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.11
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• pp.1545-1550
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• 2015

c-MYC (v-myelocytomatosis viral oncogene homologue) is a transcription factor that plays important role in many biological process including cell growth and differentiation, such as myogenesis and adipogenesis. In this study, we aimed to detect MYC gene polymorphisms, their genotype frequencies and to determine associations between these polymorphisms and meat quality traits in Berkshire pigs. We identified a single nucleotide polymorphism (SNP) in intron 2 of MYC gene by Sanger sequencing, i.e., g.3350G>C (rs321898326), that is only found in Berkshire pigs, but not in other breeds including Duroc, Landrace, and Yorkshire pigs that were used in this study. Genotypes of total 378 Berkshire pigs (138 sows and 240 boars) were determined using Hha I restriction enzyme digestion after polymerase chain reaction. Observed allele frequencies of GG, GC, and CC genotypes were 0.399, 0.508, and 0.093 respectively. Statistical analysis indicated that the g.3350G>C polymorphism was significantly associated with $pH_{45min}$ and cooking loss (p<0.05), suggesting that g.3350G>C SNP can be used for pre-selection of $pH_{45min}$ and cooking loss traits in Berkshire pigs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.449-452
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• 2013

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.

• Molecules and Cells
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• v.26 no.5
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• pp.490-495
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• 2008

Thrombophilia and hypofibrinolysis have been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor, is an important regulator of the tissue factor-mediated blood coagulation pathway. Mutations of the TFPI gene can increase the risk of thrombin generation and venous thrombosis. The aim of this study was to evaluate the association of TFPI gene polymorphisms with ONFH. All exons and their boundaries of the TFPI gene, including the -1,500 bp promoter region, were directly sequenced in 24 Korean individuals and four sequence variants were identified. These four polymorphisms [-51096 G > A (C-399T), -50984A > G (T-287C), + 24999A > G (Int7 -33T > C), + 37339T > A] were genotyped in 474 ONFH patients and 349 control subjects. The association of genotyped SNPs with ONFH was not found in the present study. The haplotype AAAT of TFPI was significantly associated with total, alcohol-induced, and idiopathic ONFH (p = 0.003, 0.021, and 0.007, respectively), and the haplotype GAAT was significantly associated with total and alcohol ONFH (p = 0.022 and 0.009, respectively). In addition, a new SNP + 37339 T > A in the 3'-UTR of the TFPI gene, was found in the Korean population. To date, this study is the first to show that haplotypes of the TFPI gene are associated with an increased susceptibility for ONFH. The results suggest that genetic variations in TFPI may play an important role in the pathogenesis and risk factors of ONFH.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5145-5151
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• 2013

Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1553-1556
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• 2012

Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A, Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.

• Korean Journal of Biological Psychiatry
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• v.19 no.2
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• pp.106-113
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• 2012

Objectives : The purpose of this study is to investigate the relationship between the triallelic serotonin transporter gene and stressful life events to determine their effect on depression with alcohol dependence. Methods : Ninety-five hospitalized patients with alcohol dependence (73 male, 22 female) were enrolled in this study. Thirty-two (33.7%) of the total patients were diagnosed with major depressive disorder and dysthymic disorder by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV. The characteristics of stress were evaluated using the stressful life events scale, and depressive symptoms were assessed using the depression scale (Beck Depression Inventory, BDI). Alcoholism with depression (n = 32) and alcoholism without depression (n = 63) were genotyped for the triallelic serotonin transporter gene ($L_A$ : higher expressing allele, $L_G$/S : lower expressing allele). Results : There was no significant difference in the allele frequency between the depression group and the non-depression group (${\chi}^2$ = 0.345, p = 0.619). $L_G$/S alleles had more comorbid depression in the higher score of stressful life events scale [Mental-Haenszel (MH)-${\chi}^2$ = 4.477, p = 0.034]. But there was no significant difference in the comorbidity according to the scores from the stressful life event scale in the $L_A$ alleles (MH-${\chi}^2$ = 0.741, p = 0.399). In the results, alcohol-dependent individuals with $L_G$/S alleles had more comorbid depression than those with $L_A$ alleles when they had experienced severe stressful life events (MH-odds ratio = 2.699, p = 0.028). Conclusions : These results suggest that there is no direct relationship between triallelic serotonin transporter gene and depression in the alcohol dependent patients. But alcohol dependent individuals with the lower expressing alleles of the serotonin transporter gene were more susceptible to depression than those with the higher expressing alleles in response to stressful life events.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.21 no.2
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• pp.116-122
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• 2011

Human occupational exposure to n-hexane has been associated with neurobehavioral symptoms such as depression, irritablity, acute irritation symptom, concentration disturbance and fatigue. Effects of monoamine oxidase (MAO) B and serotonin transporter receptor (5-HTTR) polymorphisms on the neurobehavioral symptoms were investigated in 70 male workers from TV and computer monitor manufacturing plants exposed to n-hexane. Neurobehavioral symptoms were assessed through a self-reported questionnaire and ambient level of n-hexane was measured by NIOSH method. Blood and urine were collected from each workers to determine the MAO(B), 5-HTTR and urinary 2,5-hexanedione(2,5-HD). The mean concentration of volatile n-hexane was $18.8{\pm}28.8ppm$ and that of urinary 2,5-HD was $1.07{\pm}1.47mg/g$ creatinine. Statistically significant associations with sexual disturbance were age and smoking. The frequencies of MAO(B) AA, AG and GG were 18.6%, 45.7% and 35.7%, respectively, and the frequencies of 5-HTTR ll, ls and ss genotype were 82.9%, 15.7% and 1.4%, respectively. MAO (B) gene polymorphisms had susceptibility to the neurobehavioral symptoms such as fatigue, concentration disturbance, irritability and acute irritation symptom and 5-HTTR gene polymorphism had susceptibility to the sleep disturbance and acute irritation symptom. On multiple logistic regression analysis for the neurobehavioral symptoms, memory disturbance was significantly associated with smoking(OR=6.752, 95% CI=37.46) and drinking(OR=4.033, 95% CI=1.252-12.98), emotional lability was MAO(B) genotype(OR=0.412, 95% CI=0.170-0.996), fatigue (OR=1.011, 95% CI=1.000-1.021) and acute irritation(OR=0.990, 95% CI=0.981-1.000) were working duration and sexual disturbance were significantly associated with age(OR=1.208, 95% CI=1.042-1.399), ambient n-hexane(OR=1.077, 95% CI=1.005-1.154) and 2,5-HD(OR=0.186, 95% CI=0.041-0.841). This finding implies that the MAO (B) and 5-HTTR polymorphisms may affect susceptibility for specific neurobehavioral symptoms associated with n-hexane exposure in workers.