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1.
Clin Nutr ; 37(5): 1675-1682, 2018 10.
Article in English | MEDLINE | ID: mdl-28778370

ABSTRACT

BACKGROUND & AIMS: To evaluate the relationship between phytoestrogen and colon cancer risk, we quantified plasma isoflavones (Genistein and Daidzein) and lignan (enterolactone) in a Korean nested case-control study and conducted replication study in a Vietnamese case-control study. METHODS: Study populations of 101 cases and 391 controls were selected from the Korean Multicenter Cancer Cohort which was constructed from 1993 to 2004. For replication study, Vietnamese hospital-based case-control subjects of 222 cases and 206 controls were selected from 2003 to 2007. The concentrations of plasma genistein, daidzein, and enterolactone were quantified by liquid chromatography-mass spectrometry. Logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs), and meta-analysis was conducted to estimate combined ORs (CORs) and 95% Cis of Korean and Vietnamese population in 2014. RESULTS: Genistein showed a continual decrease in colorectal cancer risk according to level up of the concentration categories in Korean and Vietnamese population (P for trend = 0.032, and 0.001, respectively) and a significantly decreased risk was found at the highest concentration of genistein and daidzein (for the highest category compared to the lowest: COR (95% CI) = 0.46 (0.30-0.69), and COR (95% CI) = 0.54 (0.36-0.82)). When the study population was stratified, the beneficial relationship of genistein with colorectal cancer was observed regardless of sex and anatomical subtype. However, enterolacton level was not associated with colorectal cancer risk. CONCLUSIONS: High plasma levels of isoflavones had relationship with a decreased risk of colorectal cancer, regardless of different ethnic background.


Subject(s)
Colorectal Neoplasms/epidemiology , Phytoestrogens/blood , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/blood , Adult , Aged , Asian People , Case-Control Studies , Colorectal Neoplasms/prevention & control , Female , Genistein/blood , Humans , Isoflavones/blood , Lignans/blood , Male , Middle Aged , Republic of Korea/epidemiology , Risk Factors , Vietnam/epidemiology
2.
Diabetologia ; 58(4): 726-35, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25533387

ABSTRACT

AIMS/HYPOTHESIS: To examine the association between soybean products and risk of type 2 diabetes, we measured four isoflavone biological markers--genistein, daidzein, glycitein and equol--in a nested case-control study. METHODS: The study population was composed of 693 cases (316 women and 377 men) and 698 matched controls (317 women and 381 men) within the Korean Genome and Epidemiology Study. The concentrations of isoflavone biomarkers were measured using HPLC-MS/MS on plasma samples that were collected at baseline. A stratified analysis was undertaken to examine the association between plasma isoflavone concentrations and risk of type 2 diabetes according to sex and equol production. Logistic regression models were used to compute ORs and 95% CIs adjusted for confounders. RESULTS: In women, compared with the lowest quartile of plasma concentration of genistein, the highest quartile exhibited a significantly decreased risk of diabetes (OR 0.58, 95% CI 0.35, 0.95). When stratified by equol-producing status in women, the OR for diabetes in the highest vs the lowest quartile of genistein concentration was 0.31 (95% CI 0.16, 0.60) in equol producers, but genistein concentration was not associated with risk of diabetes in equol non-producers (p for interaction = 0.013). In men, isoflavone concentrations were not associated with risk of diabetes, regardless of equol-producing status. CONCLUSIONS/INTERPRETATION: High plasma concentrations of genistein were associated with a decreased risk of type 2 diabetes in women. This inverse association was prominent in equol-producing participants. These results suggest a beneficial effect of a high intake of soybean products on risk of type 2 diabetes in women.


Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Diet , Isoflavones/blood , Soy Foods , Asian People/genetics , Case-Control Studies , Chi-Square Distribution , Chromatography, High Pressure Liquid , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/genetics , Equol/blood , Female , Genistein/blood , Genome, Human , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Prospective Studies , Protective Factors , Republic of Korea/epidemiology , Risk Assessment , Risk Factors , Sex Factors , Tandem Mass Spectrometry
3.
J Epidemiol ; 22(5): 433-9, 2012.
Article in English | MEDLINE | ID: mdl-22955044

ABSTRACT

BACKGROUND: In this prospective cohort study, we estimated the risk of developing more than 1 metabolic risk factor, using different obesity indices. In addition, we investigated the relative usefulness of the obesity indices for predicting development of such risk factors and calculated optimal cutoffs for the obesity indices. METHODS: The cohort comprised 10 038 representative residents of a small city and a rural county who were recruited in 2001-2002. Follow-up examinations were conducted every 2 years. Among the 3857 participants without metabolic syndrome at baseline, 1102 new cases occurred during the 6-year follow-up. Receiver operating characteristic (ROC) curves for the obesity indices were plotted to compare the usefulness of the obesity indices. RESULTS: The numbers of new cases of multiple metabolic risk factors among people in the highest quintiles of body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and waist-height ratio at the baseline examination were 2 to 3 times those in the lowest quintiles. The area under the ROC curve for WHR was significantly higher than that for BMI. The optimal BMI cutoff was 24 kg/m(2) in men and women, and the optimal WC cutoffs were 80 cm and 78 cm in men and women, respectively. CONCLUSIONS: Both overall obesity and central obesity predicted risk of developing multiple metabolic risk factors, and WHR appeared to be a better discriminator than BMI. To prevent development of metabolic diseases among Koreans, it might be useful to lower the cutoff for abdominal obesity, as defined by WC.


Subject(s)
Body Height , Body Mass Index , Metabolic Syndrome/epidemiology , Obesity/diagnosis , Waist Circumference , Waist-Hip Ratio , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity/epidemiology , Prospective Studies , ROC Curve , Reference Values , Republic of Korea/epidemiology , Risk Factors
4.
BMC Genet ; 13: 78, 2012 Sep 10.
Article in English | MEDLINE | ID: mdl-22963146

ABSTRACT

BACKGROUND: Recently, genome-wide association studies identified a pleiotropic gene locus, ABO, as being significantly associated with hematological traits. To confirm the effects of ABO on hematological traits, we examined the link between the ABO locus and hematological traits in Korean population-based cohorts. RESULTS: Six tagging SNPs for ABO were analyzed with regard to their effects on hematological traits [white blood cell count (WBC), red blood cell count (RBC), platelet (Plat), mean corpuscular volume (MCV), and mean corpuscular haemoglobin concentration (MCHC)]. Linear regression analyses were performed, controlling for recruitment center, sex, and age as covariates. Of the 6 tagging SNPs, 3 (rs2073823, rs8176720, and rs495828) and 3 (rs2073823, rs8176717, and rs687289) were significantly associated with RBC and MCV, respectively (Bonferroni correction p-value criteria < 0.05/6 = 0.008). rs2073823 and a reported SNP (rs8176746), as well as rs495828 and a reported SNP (rs651007), showed perfect linkage disequilibrium status (r2s = 0.99). Of the remaining 3 SNPs (rs8176720, rs8176717 and rs687289), rs8176717 generated an independent signal with moderate p-value (= 0.045) when it was adjusted for by rs2073823 (the most significant SNP). We also identified a copy number variation (CNV) that was tagged by the SNP rs8176717, the minor allele of which correlated with the deletion allele of CNV. Our haplotype analysis indicated that the haplotype that contained the CNV deletion was significantly associated with MCV (ß ± se = 0.363 ± 0.118, p =2.09 × 10-3). CONCLUSIONS: Our findings confirm that ABO is one of the genetic factors that are associated with hematological traits in the Korean population. This result is notable, because GWASs fail to evaluate the link between a CNV and phenotype traits.


Subject(s)
ABO Blood-Group System/genetics , Blood Physiological Phenomena/genetics , Asian People/genetics , DNA Copy Number Variations , Humans , Korea , Phenotype , Polymorphism, Single Nucleotide
5.
Genes Nutr ; 7(4): 567-74, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22477055

ABSTRACT

Equol is a daidzein (a phytoestrogen isoflavone) metabolite of gut bacteria, and the ability to produce equol varies between individuals and reduces the risks of several diseases. We tested the effects of equol production on health in Koreans and identified the genetic factors that determine the equol-producing phenotype. In 1391 subjects, the equol-producing phenotype was determined, based on measurements of serum equol concentrations. The anthropometric and blood biochemical measurements between equol producers and nonproducers were analyzed by LC-MS/MS. Genetic factors were identified in a genomewide association study (GWAS), and the interaction between genetic factors and the equol-producing phenotype was examined. We observed that 70.1 % of the study population produced equol. Blood pressure was significantly lower in equol producers (beta ± SE = -1.35 ± 0.67, p = 0.045). In our genomewide association study, we identified 5 single-nucleotide polymorphisms (p < 1 × 10(-5)) in HACE1. The most significant SNP was rs6927608, and individuals with a minor allele of rs6927608 did not produce equol (odds ratio = 0.57 (95 % CI 0.45-0.72), p value = 2.5 × 10(-6)). Notably, the interaction between equol production and the rs6927608 HACE1 SNP was significantly associated with systolic blood pressure (p value = 1.3 × 10(4)). Equol production is linked to blood pressure, and HACE1, identified in our (GWAS), might be a determinant of the equol-producing phenotype.

6.
Ann Epidemiol ; 21(1): 42-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21130368

ABSTRACT

PURPOSE: We studied a cohort of individuals to assess whether intensity of environmental tobacco smoke (ETS) exposure is associated with the incidence of type 2 diabetes. METHODS: Study subjects were selected from an ongoing population-based cohort of Korea Genome and Epidemiology Study. Participants of the baseline study 10,038 persons within the age range of 40 to 69 years old. Among 4,442 never smokers without prevalent diabetes, 465 type 2 diabetes cases were identified through biennial active follow-ups for a 6-year period. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) after adjustment for covariates. RESULTS: The risk of type 2 diabetes was higher in subjects exposed to ETS compared with the nonexposure group (HR = 1.41, 95% CI: 1.1-1.70). Daily exposure to ETS at home increased the risk of type 2 diabetes when compared with the risk level of nonexposure (HR = 1.46, 95% CI: 1.16-1.83). Over 4 hours exposure to ETS at home and in the workplace was associated with increased the risk of type 2 diabetes (HR = 1.96, 95% CI: 1.21-3.19). CONCLUSIONS: Our study suggests that ETS exposure is a significant risk factor for the development of type 2 diabetes with dose-response relationship.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Environmental Exposure/adverse effects , Tobacco Smoke Pollution/adverse effects , Adult , Aged , Cohort Studies , Female , Humans , Korea , Male , Middle Aged , Risk
7.
Cancer Epidemiol Biomarkers Prev ; 19(5): 1292-300, 2010 May.
Article in English | MEDLINE | ID: mdl-20447921

ABSTRACT

BACKGROUND: The role of soybean products in gastric cancer risk is not clear in epidemiologic studies due to measurement error from dietary intake questionnaires and due to different degrees of bias according to study design. To examine the association between soybean products and gastric cancer risk, we measured phytoestrogen biological markers in a nested case-control study. METHODS: The study population was composed of 131 cases and 393 matched controls within the Korean Multicenter Cancer Cohort. The concentrations of the four biomarkers in the plasma samples were measured using time-resolved fluoroimmunoassay. Conditional and unconditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Median plasma concentrations of genistein (229 nmol/L for controls, 181.8 nmol/L for cases; P=0.07) and daidzein (131.2 nmol/L for controls, 80.5 nmol/L for cases; P=0.04) in cases were lower than in controls, whereas equol concentrations were similar. Compared with the reference group, gastric cancer risk decreased in the highest groups for genistein (OR, 0.54; 95% CI, 0.31-0.93) and daidzein (OR, 0.21; 95% CI, 0.08-0.58). Higher equol concentrations were associated with a decreased risk for gastric cancer (OR, 0.50; 95% CI, 0.27-0.90). The combination of the highest concentrations for each isoflavone category was associated with a 0.09-fold decreased risk for gastric cancer compared with the combination of the lowest concentrations for each category. There was no association between plasma lignan concentrations and gastric cancer. CONCLUSIONS: High serum concentrations of isoflavones were associated with a decreased risk for gastric cancer. IMPACT: These results suggest a beneficial effect of high soybean product intake for gastric cancer risk.


Subject(s)
Isoflavones/therapeutic use , Phytoestrogens/therapeutic use , Stomach Neoplasms/prevention & control , Aged , Case-Control Studies , Cohort Studies , Female , Humans , Isoflavones/blood , Korea , Male , Middle Aged , Phytoestrogens/blood , Risk Factors , Soy Foods , Stomach Neoplasms/blood
9.
J Nutr ; 139(5): 1008-12, 2009 May.
Article in English | MEDLINE | ID: mdl-19321591

ABSTRACT

In this study, our aim was to investigate the association of inflammation-related genetic polymorphisms and gastric cancer risk and to examine whether the combined effect of soybean product intake modified cancer risk. Eighty-four incident gastric cancer cases and 336 matched controls were selected from the Korean Multi-Center Cancer Cohort. We selected 14 single nucleotide polymorphisms (SNP) from 5 genes [interleukin (IL)-1beta, IL-2, IL-4, IL-8, and IL-10] and used unconditional logistic regression model to calculate the odds ratios (OR) and 95% CI adjusting for H. pylori seropositivity, smoking, age, sex, enrollment year, and residential area. The risk for gastric cancer in relation to genetic polymorphisms and haplotypes were assessed according to soybean product intake levels. Although no single SNP effect was found, the combined effect between IL-10 gene variants of -592 GG/GA, -819 TC/CC, or -1082 AG/GG and low intake of soybean products had an increased risk for gastric cancer compared with the group with no risk gene variants and a high intake of soybean products (OR [95% CI] = 2.82 [1.04-7.62], 2.75 [1.02-7.44], and 4.34 [1.51-12.5], respectively). Among the low-soybean product intake group, IL-10 CCG haplotype had an increased risk of gastric cancer (OR = 3.38 [1.40-8.13]) relative to the ATA haplotype. Our results suggest that the association between IL-10 genetic polymorphisms and gastric cancer risk was modified by soybean product intake.


Subject(s)
Diet , Genetic Predisposition to Disease , Glycine max , Interleukin-10/genetics , Polymorphism, Single Nucleotide/genetics , Stomach Neoplasms/genetics , Antibodies, Bacterial/blood , Cohort Studies , Helicobacter pylori/immunology , Korea , Phytotherapy , Prospective Studies , Risk Factors , Smoking , Soy Foods , Stomach Neoplasms/microbiology , Stomach Neoplasms/prevention & control
10.
Asian Pac J Cancer Prev ; 7(2): 318-20, 2006.
Article in English | MEDLINE | ID: mdl-16839230

ABSTRACT

The purpose of this study was to test the amplification of DNA from human urinary sediment for molecular epidemiological studies. Twenty-six urine samples were obtained from healthy volunteers. Polymerase chain reactions (PCR) for methylenetetrahydrofolate reductase (MTHFR), beta-globin, and N-acetyltransferase 2 (NAT2) was conducted using genomic DNA isolated from the urine. The MTHFR and beta-globin genes were amplified successfully from all the urine DNA samples while the NAT2 gene was amplified in 88.5% of cases. The median yield of DNA was 0.28 microg from the 10 ml urine samples, sufficient amounts of DNA being contained in urinary sediments for amplification of all three genes. This result indicates that urine can be used as a DNA source for PCR-based molecular epidemiological studies.


Subject(s)
Arylamine N-Acetyltransferase/genetics , DNA/urine , Globins/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Molecular Epidemiology/methods , Polymerase Chain Reaction , Adolescent , Adult , Aged , Aged, 80 and over , Child , Feasibility Studies , Female , Humans , Male , Middle Aged , Reference Values
11.
Environ Mol Mutagen ; 45(4): 374-9, 2005 May.
Article in English | MEDLINE | ID: mdl-15657918

ABSTRACT

Squamous cell carcinoma of the head and neck (SCCHN) is a relatively rare cancer with a poor prognosis. In the present study, we investigated susceptibility biomarkers for SCCHN in 155 Koreans (73 SCCHN cases and 82 controls). Expression of the xeroderma pigmentosum group C (XPC) DNA-repair gene was measured by TaqMan fluorogenic real-time RT-PCR using RNA isolated from peripheral blood samples. In addition, the XPC-PAT genotype [an intronic and biallelic poly(AT) insertion/deletion polymorphism] was determined by PCR of peripheral blood DNA. Among known environmental and physical risk factors, age, gender, tobacco smoking, and alcohol consumption were associated with the SCCHN risk (P < 0.01). Lower XPC expression levels were found for the SCCHN cases, particularly in the larynx, than for the controls (P < 0.05); the geometric means (standard deviations) of XPC expression normalized by 18S rRNA in the cases and controls were 5.89 (8.13) and 15.14 (9.77), respectively. However, the distributions of the XPC-PAT genotypes were similar in the cases and controls. In addition, there were no associations between the expression of XPC and the PAT genetic polymorphism. XPC expression was not affected by age, gender, tobacco smoking, or alcohol consumption. After adjusting for SCCHN-associated lifestyle factors, the effective strength of XPC expression on SCCHN risk was weaker (0.05 < P < 0.1) than those of tobacco smoking and age (P < 0.05). There was a positive association between XPC mRNA expression in blood and SCCHN tissues (n = 9; P < 0.01); therefore, peripheral blood appears to be a reasonable surrogate tissue for XPC expression in tumor tissue. In conclusion, the XPC-PAT polymorphism had no effect on XPC expression or SCCHN risk. However, XPC expression may influence SCCHN risk.


Subject(s)
Carcinoma, Squamous Cell/genetics , DNA-Binding Proteins/genetics , Head and Neck Neoplasms/genetics , Adult , Biomarkers/blood , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/metabolism , Case-Control Studies , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/blood , Female , Gene Expression , Genotype , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/metabolism , Humans , Korea/ethnology , Male , Middle Aged , Polymerase Chain Reaction , RNA, Messenger/analysis , RNA, Messenger/blood , Risk Factors
12.
J Prev Med Public Health ; 37(4): 321-8, 2004 Nov.
Article in English | MEDLINE | ID: mdl-25175613

ABSTRACT

OBJECTIVES: The purpose of this study was to investigate the effect of genetic polymorphism of cytochrome P450 2E1 (CYP2E1) and aldehyde dehydrogenase 2 (ALDH2) on the xylene metabolism. METHODS: Among 247 workers, 116 were occupationally exposed to xylene and 131 were not. Workers exposed to xylene had different work such as spray, touch-up, mix & assist, and pre-treat. Questionnaire variables were age, sex, use of personal protective equipment, smoking, previous night's drinking and work duration. The urinary methylhippuric acid was measured in the urine collected in the afternoon and corrected by urinary creatinine concentration. The genotypes of CYP2E1 and ALDH2 were investigated by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods with DNA extracted from venous blood. RESULTS: 1. The urinary concentrations of o-, m-, and pmethylhippuric acid and total methylhippuric acid in the exposed group were significantly higher than those in the non-exposed group (p< 0.001). 2. In multiple regression analysis, the urinary methylhippuric acid concentration was significantly influenced by exposure grade (Job-exposure matrixes), smoking, drug use and kind of protective equipment (p< 0.1). 3. Genetic polymorphism of CYP2E1 and ALDH2 did not affect urinary methylhippuric acid level in the exposed group (p> 0.05). CONCLUSIONS: Exposure grade, smoking, drug use and kind of protective equipment affected urinary methylhippuric acid level, whereas genetic polymorphism of CYP2E1 and ALDH2 did not. However, further investigation for the effect of genetic polymorphism on the metabolism of xylene with a larger sample size is needed.

13.
Biochem Biophys Res Commun ; 312(2): 441-8, 2003 Dec 12.
Article in English | MEDLINE | ID: mdl-14637157

ABSTRACT

The metabolism of bisphenol A (BPA), a suspected endocrine disruptor, should be considered for monitoring human exposure to BPA, because the conjugation with beta-D-glucuronide and sulfate reduces the estrogenic activity. In this study, BPA levels in 30 healthy Koreans (men, N=15, 42.6+/-2.4 years; women, N=15, 43.0+/-2.7 years) were analyzed from urine treated with/without beta-glucuronidase and/or sulfatase by an RP-HPLC with fluorescence detection. The total BPA concentrations including free BPA and the urinary conjugates were similar in men and women (2.82+/-0.73 and 2.76+/-0.54 ng ml(-1), respectively), but gender differences were found in the levels of urinary BPA conjugates. Men had significantly higher levels of BPA-glucuronide (2.34+/-0.85 ng ml(-1)) than women (1.00+/-0.34 ng ml(-1)), whereas women had higher levels of BPA-sulfate (1.20+/-0.32 ng ml(-1)) than men (0.49+/-0.27 ng ml(-1)).


Subject(s)
Environmental Pollutants/urine , Glucuronidase/chemistry , Phenols/chemistry , Phenols/urine , Sulfatases/chemistry , Urinalysis/methods , Adult , Benzhydryl Compounds , Chromatography, High Pressure Liquid/methods , Female , Humans , Male , Phenols/metabolism , Protein Binding , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Fluorescence/methods
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