• Title/Summary/Keyword: Molecular Epidemiology

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Sex Differences in Cancer: Epidemiology, Genetics and Therapy

  • Kim, Hae-In;Lim, Hyesol;Moon, Aree
    • Biomolecules & Therapeutics
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    • v.26 no.4
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    • pp.335-342
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    • 2018
  • The incidence and mortality of various cancers are associated with sex-specific disparities. Sex differences in cancer epidemiology are one of the most significant findings. Men are more prone to die from cancer, particularly hematological malignancies. Sex difference in cancer incidence is attributed to regulation at the genetic/molecular level and sex hormones such as estrogen. At the genetic/molecular level, gene polymorphism and altered enzymes involving drug metabolism generate differences in cancer incidence between men and women. Sex hormones modulate gene expression in various cancers. Genetic or hormonal differences between men and women determine the effect of chemotherapy. Until today, animal studies and clinical trials investigating chemotherapy showed sex imbalance. Chemotherapy has been used without consideration of sex differences, resulting in disparity of efficacy and toxicity between sexes. Based on accumulating evidence supporting sex differences in chemotherapy, all clinical trials in cancer must incorporate sex differences for a better understanding of biological differences between men and women. In the present review, we summarized the sex differences in (1) incidence and mortality of cancer, (2) genetic and molecular basis of cancer, (3) sex hormones in cancer incidence, and (4) efficacy and toxicity of chemotherapy. This review provides useful information for sex-based chemotherapy and development of personalized therapeutic strategies against cancer.

Identification and Application of Biomarkers in Molecular and Genomic Epidemiologic Research

  • Lee, Kyoung-Mu;Han, So-Hee;Park, Woong-Yang;Kang, Dae-Hee
    • Journal of Preventive Medicine and Public Health
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    • v.42 no.6
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    • pp.349-355
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    • 2009
  • Biomarkers are characteristic biological properties that can be detected and measured in a variety of biological matrices in the human body, including the blood and tissue, to give an indication of whether there is a threat of disease, if a disease already exists, or how such a disease may develop in an individual case. Along the continuum from exposure to clinical disease and progression, exposure, internal dose, biologically effective dose, early biological effect, altered structure and/or function, clinical disease, and disease progression can potentially be observed and quantified using biomarkers. While the traditional discovery of biomarkers has been a slow process, the advent of molecular and genomic medicine has resulted in explosive growth in the discovery of new biomarkers. In this review, issues in evaluating biomarkers will be discussed and the biomarkers of environmental exposure, early biologic effect, and susceptibility identified and validated in epidemiological studies will be summarized. The spectrum of genomic approaches currently used to identify and apply biomarkers and strategies to validate genomic biomarkers will also be discussed.

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

  • Farahani, Roya Kishani;Azimzadeh, Pedram;Rostami, Elham;Malekpour, Habib;Aghdae, Hamid Asadzadeh;Pourhoseingholi, Mohamad Amin;Mojarad, Ehsan Nazemalhosseini;Zali, Mohammad Reza
    • 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.

Association Between VDR Polymorphisms and Breast Cancer: An Updated and Comparative Meta-analysis of Crude and Adjusted Odd Ratios

  • Huang, Qian-Qian;Liao, Yu-Yi;Ye, Xiao-Hua;Fu, Jin-Jian;Chen, Si-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.847-853
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    • 2014
  • There is a lot of debate on the relationship between vitamin D receptor polymorphisms and risk of breast cancer. Herein, we quantitatively analyzed the published case-control studies on this relationship by meta-analysis, performing a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included case-control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19, 20, 10, 4, 6, respectively. Crude and adjusted odd ratios and 95% confidence intervals were calculated to present and compare the strength of any associations. The results of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2 and Poly-A were not significantly associated with the risk of breast cancer. In contrast, the tt genotype of Taq1 was a modest risk factor for breast cancer development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the above results, adjusted effects for the six polymorphisms were pooled based on adjusted ORs reported in the original studies. Adjusted ORs of Fok1, Apa1, Cdx2 and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1 showed inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for Taq1, OR for tt vs. TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk. Subgroup analyses for crude ORs showed some association between Bsm1, Taq1 and breast cancer in Caucasians only, but for adjusted ORs, no associations were found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions. To be conservative, we still assumed that they may play a modest role in determining breast cancer risk. Further studies are needed to validate our findings.

Survey of Asbestos-Related Disease on Chest Radiograph of Workers Exposed to Asbestos in Ship Repair (조선수리업종 석면노출 근로자들의 흉부방사선상 석면관련 폐질환 소견의 발생양상)

  • Lee Hyun Jae;Hong Young Seoub;Son Ji Eun;Lee Young Ill;Kim Sang Hoon;Im Hyoung June;Kim Jung Man;Kim Joon Youn
    • Journal of Life Science
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    • v.16 no.1
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    • pp.58-63
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    • 2006
  • There was cross-sectional study on investigating the factors related asbestos-related disease on chest radiograph of workers exposed to asbestos in ship repair. According to Occupational Safety & Health Administration asbestos standard, medical surveillance, chest radiologic study, pulmonary function test and medical questionnaire are performed in 118 subjects exposed to asbestos for 10 years or more in ship repair. The sixteen out of 118 subjects $(13.6\%)$ were observed asbestos-related disease finding on chest radiography. Significant factors related to those finding on chest radiography were abnormal pulmonary function test, cough, sputum, past history of respiratory disease, work duration. Workers with Significant factors related asbestos-related disease finding on chest radiography should be managed on a strict program. Further, factors unrelated with asbestos-related disease finding on this study should be evaluated prospectively for medical surveillance program of workers exposed to asbestos.

BcSNPdb: Bovine Coding Region Single Nucleotide Polymorphisms Located Proximal to Quantitative Trait Loci

  • Moon, Sun-Jin;Shin, Hyoung-Doo;Cheong, Hyun-Sub;Cho, Hye-Young;NamGoong, Sohg;Kim, Eun-Mi;Han, Chang-Su;Sung, Sam-Sun;Kim, Hee-Bal
    • BMB Reports
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    • v.40 no.1
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    • pp.95-99
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    • 2007
  • Bovine coding region single nucleotide polymorphisms located proximal to quantitative trait loci were identified to facilitate bovine QTL fine mapping research. A total of 692,763 bovine SNPs was extracted from 39,432 UniGene clusters, and 53,446 candidate SNPs were found to be a depth >3. In order to validate the in silico SNPs experimentally, 186 animals representing 14 breeds and 100 mixed breeds were analyzed. Genotyping of 40 randomly selected candidate SNPs revealed that 43% of these SNPs ranged in frequency from 0.009 to 0.498. To identify non-synonymous SNPs and to correct for possible frameshift errors in the ESTs at the predicted SNP positions, we designed a program that determines coding regions by protein-sequence referencing, and identified 17,735 nsSNPs. The SNPs and bovine quantitative traits loci informations were integrated into a bovine SNP data: BcSNPdb (http://snugenome.snu.ac.kr/BtcSNP/). Currently there are 43 different kinds of quantitative traits available. Thus, these SNPs would serve as valuable resources for exploiting genomic variation that influence economically and agriculturally important traits in cows.

ADFP promoter polymorphism associated with marbling score in Korean cattle

  • Cheong, Hyun-Sub;Yoon, Du-Hak;Bae, Joon-Seol;Kim, Lyoung-Hyo;Kim, Eun-Mi;Kim, Ji-On;Hong, Jin;Kim, Nae-Soo;Shin, Hyoung-Doo
    • BMB Reports
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    • v.42 no.8
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    • pp.529-534
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    • 2009
  • Marbling score (MS) is the major trait that affects carcass quality in beef cattle. In this study, we investigated the association between genetic polymorphisms of the adipose differentiation-related protein gene (ADFP) and carcass traits in Korean cattle (also known as Hanwoo). Using direct DNA sequencing in 24 unrelated Korean cattle, 25 novel polymorphisms were identified within all exons and their flanking regions of ADFP, including the promoter region (1.5 kb). Among them, 21 polymorphic sites were selected for genotyping in the beef cattle (n = 425). Statistical analyses revealed that one promoter polymorphism (c.-56-18A > G) was associated with MS (P = 0.009). The 'A' allele of c.-56-18A > G exerted a lowering effect on MS, e.g., the lowest MS was found in 'A/A' (MS = 2.09 ${\pm}$ 1.23), intermediate in 'A/G' (MS = 2.11 ${\pm}$ 1.31), and the highest in 'G/G' (MS = 2.47 ${\pm}$ 1.47). Our findings suggest that these polymorphisms in ADFP might be important genetic factors involved in carcass quality in beef cattle.

Survival Time and Molecular Subtypes of Breast Cancer after Radiotherapy in Thailand

  • Kongsiang, Apichat;Tangvoraphonkchai, Vorachai;Jirapornkul, Chananya;Promthet, Supannee;Kamsa-ard, Siriporn;Suwanrungruang, Krittika
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10505-10508
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    • 2015
  • Background: Breast cancer is an important cause of death among women. One way of classifying different forms of breast cancer is by molecular features, usually in terms of the four subtypes: luminal A, luminal B, HER2-enriched, and triple negative. Objectives: This study aimed to investigate the association between molecular subtypes and survival among breast cancer patients treated with radiotherapy. Materials and Methods: A retrospective cohort study was conducted. The subjects were 272 breast cancer patients who had received treatment in the radiotherapy unit at Srinagarind Hospital, Thailand, between 1 January, 1999, and 31 May, 2009. The end of the study was 1 June, 2014. Overall survival was defined as the time elapsing between initial registration at the radiotherapy unit and death or the end of the study. Survival curves were estimated by the Kaplan-Meier method, and a multivariate analysis was performed using Cox's proportional hazard regression model. Results: The patient mean age was $47.5{\pm}10.4$ at the time of diagnosis. Of the 272 patients, 146 (53.7%) were classified as luminal A, 12 (4.4%) as luminal B, 30 (11.0%) as HER2-enriched, and 84 (30.9%) as triple negative. The overall survival rates at 1, 3 and 5 years were 87.1%, 68.4% and 59.2%, respectively. According to molecular subtypes, HER2-enriched patients had the lowest 5-year survival rate (30.0 %, 95%CI: 15.02-46.55). The median follow-up time was 8.37 years. In the Cox model analysis a higher risk of death was found for patients with HER2-enriched ($HR_{adj}=3.34$, 95%CI:1.96-5.67), triple negative ($HR_{adj}=2.17$, 95%CI: 1.44-3.27), and stage IIlB ($HR_{adj}=2.20$, 95%CI: 1.16-4.17) cancers. Conclusions: The worst survival rates were among patients classified as HER2-enriched, triple negative and at stage IIIB. Early detection and an advanced treatment modality are needed to help these patients.

Molecular epidemiology and cancer susceptibility -Genetic polymorphisms and susceptibility to urothelial cancer-

  • Katoh, Takahiko
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.21-22
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    • 2003
  • Arylamines are suspected to be the primary causative agent of urothelial cancer in tobacco smoke. In the human liver, arylamines are N-hydroxylated by a cytochrome P450 (CYP) 1A2-catalyzed reaction, which produces a substrate for O-esterification that can be catalyzed by N-acetylatransferases (NAT) or sulfotransferases (SULT). (omitted)

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Characteristics of the Molecular Epidemiology of CTX-M-Producing Escherichia coli Isolated from a Tertiary Hospital in Daejeon, Korea

  • Kim, Semi;Sung, Ji Youn;Cho, Hye Hyun;Kwon, Kye Chul;Koo, Sun Hoe
    • Journal of Microbiology and Biotechnology
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    • v.26 no.9
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    • pp.1643-1649
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    • 2016
  • The aims of this study were to characterize the molecular epidemiological profiles of CTX-M-producing uropathogenic Escherichia coli isolates from a tertiary hospital in Daejeon, Korea, and to investigate the genetic diversity and compare the prevalence of sequence types (STs) in different areas. Extended spectrum β-lactamase-producing E. coli strains isolated from urine were analyzed for CTX-M, integrons, and insertion sequence common regions (ISCRs) by PCR and sequencing. Multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), phylogenetic analysis, and rep-PCR were also used for molecular typing of the isolates. Of 80 CTX-M producers, 31 and 46 expressed CTX-M-15 and CTX-M-14, respectively. MLST analysis indicated that the most prevalent ST was ST131 (n = 34, 42.5%), followed by ST38 (n = 22, 27.5%), ST405 (n = 8, 10.0%), and ST69 (n = 6, 7.5%). Most CTX-M producers harbored class 1 integrons. ST131 strains belonged to phylogenetic group B2 and showed identical rep-PCR patterns, whereas ST69, ST38, and ST405 strains belonged to phylogenetic group D; the ST38 and ST405 strains displayed the same rep-PCR pattern, respectively. ST131 and ST38 isolates showed 21 and 19 distinct types, respectively, by PFGE. In Daejeon, D-ST38 CTX-M-14 producers were relatively more prevalent than in other countries and Korean cities. Our results indicate that CTX-M-producing E. coli isolates belonged mostly to ST131 or ST38 and were more related to hospital-onset than to community-onset infections and that the blaCTX-M gene may vary according to the ST.