• Genomics & Informatics
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• 제10권3호
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• pp.175-183
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• 2012

Colorectal cancer (CRC) is among the leading causes of cancer deaths and can be caused by environmental factors as well as genetic factors. Therefore, we developed a prediction model of CRC using genetic risk scores (GRS) and evaluated the effects of conventional risk factors, including family history of CRC, in combination with GRS on the risk of CRC in Koreans. This study included 187 cases (men, 133; women, 54) and 976 controls (men, 554; women, 422). GRS were calculated with most significantly associated single-nucleotide polymorphism with CRC through a genomewide association study. The area under the curve (AUC) increased by 0.5% to 5.2% when either counted or weighted GRS was added to a prediction model consisting of age alone (AUC 0.687 for men, 0.598 for women) or age and family history of CRC (AUC 0.692 for men, 0.603 for women) for both men and women. Furthermore, the risk of CRC significantly increased for individuals with a family history of CRC in the highest quartile of GRS when compared to subjects without a family history of CRC in the lowest quartile of GRS (counted GRS odds ratio [OR], 47.9; 95% confidence interval [CI], 4.9 to 471.8 for men; OR, 22.3; 95% CI, 1.4 to 344.2 for women) (weighted GRS OR, 35.9; 95% CI, 5.9 to 218.2 for men; OR, 18.1, 95% CI, 3.7 to 88.1 for women). Our findings suggest that in Koreans, especially in Korean men, GRS improve the prediction of CRC when considered in conjunction with age and family history of CRC.

• Genomics & Informatics
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• 제11권1호
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• pp.46-51
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• 2013

Normal-karyotype acute myeloid leukemia (NK-AML) is a highly malignant and cytogenetically heterogeneous hematologic cancer. We searched for somatic mutations from 10 pairs of tumor and normal cells by using a highly efficient and reliable analysis workflow for whole-exome sequencing data and performed association tests between the NK-AML and somatic mutations. We identified 21 nonsynonymous single nucleotide variants (SNVs) located in a coding region of 18 genes. Among them, the SNVs of three leukemia-related genes (MUC4, CNTNAP2, and GNAS) reported in previous studies were replicated in this study. We conducted stepwise genetic risk score (GRS) models composed of the NK-AML susceptible variants and evaluated the prediction accuracy of each GRS model by computing the area under the receiver operating characteristic curve (AUC). The GRS model that was composed of five SNVs (rs75156964, rs56213454, rs6604516, rs10888338, and rs2443878) showed 100% prediction accuracy, and the combined effect of the three reported genes was validated in the current study (AUC, 0.98; 95% confidence interval, 0.92 to 1.00). Further study with large sample sizes is warranted to validate the combined effect of these somatic point mutations, and the discovery of novel markers may provide an opportunity to develop novel diagnostic and therapeutic targets for NK-AML.

• 대한의생명과학회지
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• 제18권3호
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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.

• Journal of Genetic Medicine
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• 제12권2호
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• pp.85-91
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• 2015

Purpose: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. Materials and Methods: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. Results: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. Conclusion: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.

• Asian-Australasian Journal of Animal Sciences
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• 제30권6호
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• pp.765-772
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• 2017

Objective: This study examines the genetic factors influencing the phenotypes (four economic traits:oleic acid [C18:1], monounsaturated fatty acids, carcass weight, and marbling score) of Hanwoo. Methods: To enhance the accuracy of the genetic analysis, the study proposes a new statistical model that excludes environmental factors. A statistically adjusted, analysis of covariance model of environmental and genetic factors was developed, and estimated environmental effects (covariate effects of age and effects of calving farms) were excluded from the model. Results: The accuracy was compared before and after adjustment. The accuracy of the best single nucleotide polymorphism (SNP) in C18:1 increased from 60.16% to 74.26%, and that of the two-factor interaction increased from 58.69% to 87.19%. Also, superior SNPs and SNP interactions were identified using the multifactor dimensionality reduction method in Table 1 to 4. Finally, high- and low-risk genotypes were compared based on their mean scores for each trait. Conclusion: The proposed method significantly improved the analysis accuracy and identified superior gene-gene interactions and genotypes for each of the four economic traits of Hanwoo.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.815-821
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• 2016

Background: Development of chronic myeloid leukemia (CML) involves formation of double strand breaks (DSBs) which are initially sensed by the ataxia telangiectasia mutated (ATM) signal kinase to induce a DNA damage response (DDR). Mutations or single nucleotide polymorphisms in ATM gene are known to influence the signaling capacity resulting in susceptibility to certain genetic diseases such as cancers. Materials and Methods: In the present study, we have analyzed -5144A>T (rs228589) and C4138T (rs3092856) polymorphisms of theATM gene through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 925 subjects (476 CML cases and 449 controls). Results: The A allele of -5144A>T polymorphism and T allele of C4138T polymorphism which were known to be influencing ATM signaling capacity are significantly associated with enhanced risk for CML independently and also in combination (evident from the haplotype and diplotype analyses). Significant elevation in the frequencies of both the risk alleles among high risk groups under European Treatment and Outcome Study (EUTOS) score suggests the possible role of these polymorphisms in predicting the prognosis of CML patients. Conclusions: This study provides the first evidence of association of functional ATM gene polymorphisms with the increased risk of CML development as well as progression.

• 종양간호연구
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• 제11권2호
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• pp.147-154
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• 2011

Purpose: This study was performed to evaluate Korean nurses' knowledge about hereditary colorectal cancer (HCRC). Methods: A modified 15-item HCRC knowledge questionnaire was developed based on previous research. One hundred and forty-eight nurses have completed the questionnaire from February to April, 2011. Results: The average score of nurses' knowledge was $11.25{\pm}1.54$. Ninety-seven percent of nurses knew about colonoscopy check up schedule and family pedigree. However, only 20% of nurses knew about the rate of passing on mutation genes to offspring and risk of developing CRC among carriers. Only 13.5% of nurses had previous genetic education experiences. Working in oncology units, taking care of CRC patients, and participating in genetic education were not associated with nurses' HCRC knowledge. Conclusion: Various factors influence nurses' knowledge about HCRC. Repeated study with larger national sample of nurses is recommended to identify the factors affecting nurses' knowledge level in order to develop efficient genetic education programs for HCRC patients and their families by nurses.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1539-1546
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• 2016

Specific patterns of the hereditary breast and ovarian cancer (HBOC) syndrome are related to mutations in the BRCA1 gene. One hundred unrelated breast cancer patients were interviewed to obtain clinical symptoms and signs, pedigree and familial history of HBOC syndrome related cancer. Subsequently, data were calculated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk prediction model. Patients with high score of BOADICEA were offered genetic testing. Eleven patients with high score of BOADICEA, 2 patients with low score of BOADICEA, 2 patient's family members and 15 controls underwent BRCA1 genetic testing. Mutation screening using PCR-HRM was carried out in 22 exons (41 amplicons) of BRCA1 gene. Sanger sequencing was subjected in all samples with aberrant graph. This study identified 10 variants in the BRCA1 gene, consisting of 6 missense mutations (c.1480C>A, c.2612C>T, c.2566T>C, c.3113A>G, c.3548 A>G, c.4837 A>G), 3 synonymous mutations (c.2082 C>T, c.2311 T>C and c.4308T>C) and one intronic mutation (c.134+35 G>T). All variants tend to be polymorphisms and unclassified variants. However, no known pathogenic mutations were found.

• 한국환경보건학회지
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• 제41권4호
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• pp.249-258
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• 2015

Objectives: This study aims to investigate the correlations between the prevalence of allergic rhinitis (AR) and cytokines among elementary school children in an industrial city, Ulsan, South Korea, and to identify major environmental risk factors associated with AR prevalence. Methods: We conducted a case-control study in June 2009 and February 2010 in order to evaluate the relationship between AR and related cytokines. Data on physician-treated prevalence over the past 12 months and potential risk factors for AR were compiled through a questionnaire from a survey of 339 schoolchildren living in different urban environments. Logistic regression analysis was carried out with propensity score matched data (n=180) to assess the influences of cytokines (IL-13, IL-33, IL-4 and IL-5) on AR prevalence and to determine which environmental factors affected AR. Results: In univariate analysis, the AR prevalence was influenced by family history of AR (mother and siblings), environmental factors (odor condition and irritated symptoms of air pollution), and indoor allergens (D. farinae and D. pteronyssinus). The t-test demonstrated that eosinophils, Immunoglobulin E (IgE), and interleukins (IL-13 and IL-5) were statistically significantly different according to treatment of allergic rhinitis over the preceeding 12 months. The results of the multiple logistic regression analysis showed that a statistically significant association between several factors (such as irritated symptoms of air pollution (OR 4.075, CI 1.735-9.568), IL-13 (OR 0.825, CI 0.734-0.928), odor condition (OR 2.409, CI 0.908-6.389), and AR history of siblings (OR 2.217, CI 0.999-4.921)) and the prevalence of AR was found after adjusting for confounders. Conclusion: These results suggest that AR prevalence is significantly associated with cytokine level, genetic background, and outdoor environmental factors. Although living in a polluted area and genetic background can contribute to an increased risk of childhood AR, cytokine level should be considered as an important factor in the treatment of AR in the last 12 months.

• 성인간호학회지
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• 제20권6호
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• pp.815-828
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• 2008

Purpose: This study was to develop and evaluate the clinical utility of the breast and ovarian cancer genetic counselling program specific for 20 Korean women(KBOCGP). Methods: The KBOCGP was developed using three types of approaches: an ethnography among Korean women who underwent BRCA1/2 test, designing and implementing one week clinical genetic educational course for clinical cancer nurses, educational observation visits to three American cancer genetic counselling programs. And then pre-experimental design was implicated to evaluate the change of the women's knowledge about the hereditary breast and ovarian cancer and the level of the satisfaction with genetic counselling. Results: The mean score of the knowledge has significantly increased from $7.45{\pm}3.86$ to $11.55{\pm}2.21$ (t = 5.63, p < .001). The level of the satisfaction with the counselling was very high ($27.47{\pm}1.35$). Because most of the subjects have young kids, they showed strong concerns about their kids' getting cancer. Conclusion: This new KBOCGP is the satisfactory program for the education and communication of the genetic information to the Korean women with HBOC. But it is needed more to strengthen the cultural sensitivity especially to Korean family relationships. Authors recommend that this program be provided by other nurses who are counselling women at high risk of breast cancer.