• Genomics & Informatics
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• v.14 no.4
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• pp.138-148
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• 2016

The success of genome-wide association studies (GWASs) has enabled us to improve risk assessment and provide novel genetic variants for diagnosis, prevention, and treatment. However, most variants discovered by GWASs have been reported to have very small effect sizes on complex human diseases, which has been a big hurdle in building risk prediction models. Recently, many statistical approaches based on penalized regression have been developed to solve the "large p and small n" problem. In this report, we evaluated the performance of several statistical methods for predicting a binary trait: stepwise logistic regression (SLR), least absolute shrinkage and selection operator (LASSO), and Elastic-Net (EN). We first built a prediction model by combining variable selection and prediction methods for type 2 diabetes using Affymetrix Genome-Wide Human SNP Array 5.0 from the Korean Association Resource project. We assessed the risk prediction performance using area under the receiver operating characteristic curve (AUC) for the internal and external validation datasets. In the internal validation, SLR-LASSO and SLR-EN tended to yield more accurate predictions than other combinations. During the external validation, the SLR-SLR and SLR-EN combinations achieved the highest AUC of 0.726. We propose these combinations as a potentially powerful risk prediction model for type 2 diabetes.

• Toxicological Research
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• v.19 no.1
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• pp.1-12
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• 2003

New breeding method by genetic engineering is expected as a key technology to solve food shortage due to the growing world population in the year 2000s. Many genetically modified organisms (GMOs) were already developed and the commercial cultivation had started. The first GMO, Flavr Savr tomato, which rotted at a much slower pace than ordinary ones, was developed in US in 1994. Since then, over than 70 different agricultural products including corn, cotton, soybean, papaya, potato, and squash made with genetically modified plants are reportedly on sale worldwide. Supporters favor the GMOs because they have greater yields, longer shelf lives and stronger resistance to disease and insects. On the other hand, opponents say that the supporters ignore a potential danger that they may damage the environment as well as human beings. To assure the safe development and use of GMOs as food and other biotech products, the possible risks on biological environment and human health should be throughly examined and regulated by developer and government. Because the biosafety problem is a global, environmental, and trade issue, a new international treaty is under development. The Cartagena Protocol on Biosafety was adopted at the 1 st Extraordinary Conference of Parties of the Convention on Biological Diversity which was held at Mont-real, Canada, Jan. 29th, 2000. The adoption of the Protocol is seen as a breakthrough in that it is based on the" Precautionary Principle" despite scientific uncertainties surrounding potential risks that GMOs may inflict on human health and the environment and that it has laid the ground for introduction of specific steps to handle international trading of GMOs. In this paper, the authors would like to introduce the current status and perspective of environmental and human risk assessment of GMOs.t of GMOs.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.43 no.5
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• pp.462-473
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• 2010

Inductions of hybrids and reciprocal hybrids between Oryzias dancena and O. javanicus (ODJ and OJD) were conducted and backcross hybrids between female O. dancena and male ODJ were also produced for biological and cytogenetic analysis. Embryonic development of ODJ and OJD were compared with those of their parents. Developmental time was fastest in O. dancena and ODJ, followed by O. javanicus and OJD. Oryzias dancena hatched 11 days (d) after fertilization, ODJ at 13 d, O. javanicus at 14 d and OJD at 15 d. The abnormality of external morphology rate in ODJ was 10.6%; however, OJD showed a high degree of abnormality, over 90%. The proportion of males was 90.0% and 31.3% for ODJ and OJD, respectively. Cytogenetic analysis was conducted to obtain basic information for genetic identification of O. dancena, O. javanicus and their hybrids. The karyotypes of all experimental groups showed 2n=48 chromosomes and the fundamental number (FN) was 48. The first pair carried secondary constrictions near the centromeric regions. Erythrocyte area and volume were $9.8\;{\pm}\;0.5\;{\mu}m^2$ and $18.2\;{\pm}\;1.0\;{\mu}m^3$, respectively, for O. dancena, $8.3\;{\pm}\;0.5\;{\mu}m^2$ and $15.8\;{\pm}\;1.5\;{\mu}m^3$ in O. javanicus, and $18.3\;{\pm}\;0.5\;{\mu}m^2$ and $15.7\;{\pm}\;1.3\;{\mu}m^3$ in ODJ. Erythrocyte area and volume in ODJ were similar to those of O. javanicus. In backcross hybrids between female O. dancena and male ODJ, all embryos failed to develop and died in the late gastrula stage.

• Journal of Plant Biotechnology
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• v.35 no.1
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• pp.23-29
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• 2008

Development of genetically modified crops using modern biotechnology is regarded as a promising way to combat with ever-increasing human population. Korea attempted to develop its own genetically modified crops essentially for the past 20 years, however no example of commercialization has been announced. Here, I briefly summarized current status of development and risk assessment of genetically modified crops in Korea. Then, I attempted to identify a death valley in the process of commercialization. Based on experience of risk assessment of 15 different genetically modified organisms, I suggested that lack of the screening of elite events may serve as a death valley.

• Ocean and Polar Research
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• v.30 no.1
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• pp.109-117
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• 2008

Application of biomarkers for assessing marine environmental health risk is a relatively new field. According to the National Research Council and the World Health Organization, biomarkers can be divided into three classes: biomarkers of exposure, biomarkers of effect, and biomarkers of susceptibility. In order to assess exposure to or effect of the environmental pollutants on marine ecosystem, the following set of biomarkers can be examined: detoxification, oxidative stress, biotransformation products, stress responses, apoptosis, physiological metabolisms, neuromuscular responses, reproductions, steroid hormones, antioxidants, genetic modifications. Since early 1990s, several biomarker research groups have developed health indices of marine organisms to be used for assessing the state of the marine environment. Biomarker indices can be used to interpret data obtained from monitoring biological effects. In this review, we will summarize Health assessment Index, Biomarker Index, Bioeffect Assessment Index and Generalized Linear Model. Measurements of biomarker responses and development of biomarker index in marine organisms from contaminated sites offer great a lot of information, which can be used in environmental monitoring programs, designed for various aspects of ecosystem risk assessment.

• Toxicological Research
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• v.34 no.4
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• pp.303-310
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• 2018

The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4-position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machine-generated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA's BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a two-fold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA's BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.

• Biomedical Science Letters
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• v.18 no.3
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• pp.244-253
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• 2012

Bone mineral density (BMD) is used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. Osteoporosis, characterized mainly by decreased BMD, is a highly heritable complex disorder and a major public health concern to hundreds of millions of elderly persons worldwide. However, the specific genetic variants determining risk for low bone density are still largely unknown. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in ESR1 gene with low bone density. By examining genotype data of a total of 1813 women in the Korean Association REsource (KARE) study, we discovered the ESR1 gene polymorphisms are associated with decreased BMD and osteoporosis. The results on the BD-RT (bone density estimated by T-score at distal radius), three SNPs (rs2248586, rs9371557, and rs1569788) within the ESR1 gene were significantly associated with bone density. The results on the BD-TT (bone density estimated by T-score at midshaft tibia), five SNPs (rs9371552, rs2248586, rs712221, rs7772475, and rs3798577) were significantly associated with bone density. The SNP rs2248586 within the ESR1 gene had commonly significance in both BD-RT (${\beta}$=-0.151, dominant P=0.049) and BD-TT (${\beta}$=-0.156, dominant P=0.039). In the SNP rs2248586, their ${\beta}$-values in BD-RT and/or BD-TT showed consistent trends with the odds ratios (ORs) of osteoporosis. In summary, we found statistically significant SNPs in ESR1 gene that are associated with both decreased BMD and osteoporosis traits. Therefore, our findings suggest ESR1 gene could be related to pathogenesis of osteoporosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1937-1943
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• 2013

Altered expression or function of manganese superoxide dismutase (MnSOD) has been shown to be associated with cancer risk but assessment of gene polymorphisms has resulted in inconclusive data. Here a search of published data was made and 22 studies were recruited, covering 20,025 case and control subjects, for meta-analyses of the association of MnSOD polymorphisms with the risk of prostate, esophageal, and lung cancers. The data on 12 studies of prostate cancer (including 4,182 cases and 6,885 controls) showed a statistically significant association with the risk of development in co-dominant models and dominant models, but not in the recessive model. Subgroup analysis showed there was no statistically significant association of MnSOD polymorphisms with aggressive or nonaggressive prostate cancer in different genetic models. In addition, the data on four studies of esophageal cancer containing 620 cases and 909 controls showed a statistically significant association between MnSOD polymorphisms and risk in all comparison models. In contrast, the data on six studies of lung cancer with 3,375 cases and 4,050 controls showed that MnSOD polymorphisms were significantly associated with the decreased risk of lung cancer in the homozygote and dominant models, but not the heterozygote model. A subgroup analysis of the combination of MnSOD polymorphisms with tobacco smokers did not show any significant association with lung cancer risk, histological type, or clinical stage of lung cancer. The data from the current study indicated that the Ala allele MnSOD polymorphism is associated with increased risk of prostate and esophageal cancers, but with decreased risk of lung cancer. The underlying molecular mechanisms warrant further investigation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.591-595
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• 2016

The liver is one of the most common sites of cancer in the world, hepatocellular carcinoma (HCC) predominating. Chronic hepatitis B virus infection (CHB) is considered as an important potential risk factors for HCC. Different people have diverse responses to HBV infection regarding the likelihood of HCC development, and host factors such as single nucleotide polymorphisms (SNPs) might account for this. The present study was conducted to evaluate any association between SNP frequencies in two genes, XRCC4 (rs1805377) and ATF6 (rs2070150), and the risk of CHB and HCC development in Thai patients. The study covered 369 subjects including 121 HCC patients, 141 with chronic hepatitis B virus infection (CHB) and 107 healthy controls. With TaqMan real-time PCR, the results showed that no significant association between XRCC4 (rs1805377) and ATF6 (rs2070150) and risk of HCC in the Thai population. From this first study of the 2 polymorphisms and HCC in Thailand it can concluded that rs1805377 and rs2070150 polymorphisms may not be applicable as genetic markers in the Thai population for HCC assessment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4305-4309
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• 2012

Background: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of the association by meta-analysis. Methods: We searched PubMed and Wangfang databases for published studies on the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for assessment. Results: 10 studies with a total of 2,026 cases and 2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism was not associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidence of publication bias was observed. Conclusion: Meta-analyses of available data suggest an obvious association between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism may have a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.