Kwang-Pil Ko

Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: Systematic review and meta‐analysis

A subadditive effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is possible because superinfection of one virus tends to inhibit infection of the other virus. However, studies have reported inconsistent findings, and two meta‐analyses of studies from various countries (1998) and China (2005) reported a supraadditive effect for hepatocellular carcinoma (HCC) risk. Thus, we reevaluate HBV/HCV monoinfection and coinfection. Of 411 reports, we included 59 studies that assessed the association between HBV/HCV monoinfection and coinfection for HCC risk. HCC risk because of high/detectable HBV DNA and HBeAg infection was higher than HBsAg infection, whereas anti‐HCV vs anti‐HCV/HCV RNA was not different. Geographically, HCC risk was significantly higher in nonendemic than in HBV or HCV endemic areas. Subadditive effect for HCC risk was presented in recently published studies, cohort studies and studies conducted in HBV/HCV nonendemic areas; an additive effect was presented in studies conducted in HBV endemic areas; a supraadditive effect was presented in previously published studies, case‐control studies and studies conducted in HCV endemic areas. Our results suggest HBV/HCV coinfection for HCC risk is not significantly greater than HBV/HCV monoinfection, and HCC risk due to HBV or HCV is higher in nonendemic than endemic areas. The p‐heterogeneity was significant for most analyses, except HBV(+)/HCV(+) and HBV biomarker analyses. Prevention strategies targeted toward HBV or HCV monoinfected patients are needed. In addition, tailored prevention to reduce infectivity such as HBV markers (HBeAg, HBV DNA) is needed.

Isoflavones from Phytoestrogens and Gastric Cancer Risk: A Nested Case-Control Study within the Korean Multicenter Cancer Cohort

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. Cancer Epidemiol Biomarkers Prev; 19(5); 1292–300. ©2010 AACR.

The role of TNF genetic variants and the interaction with cigarette smoking for gastric cancer risk: a nested case-control study

BackgroundThe aim of this study was to investigate the role of TNF genetic variants and the combined effect between TNF gene and cigarette smoking in the development of gastric cancer in the Korean population.MethodsWe selected 84 incident gastric cancer cases and 336 matched controls nested within the Korean Multi-Center Cancer Cohort. Six SNPs on the TNF gene, TNF-α-238 G/A, -308 G/A, -857 C/T, -863 C/A, -1031 T/C, and TNF-β 252 A/G were genotyped. The ORs (95% CIs) were calculated using unconditional logistic regression model to detect each SNP and haplotype-pair effects for gastric cancer. The combined effects between the TNF gene and smoking on gastric cancer risk were also evaluated. Multi dimensionality reduction (MDR) analyses were performed to explore the potential TNF gene-gene interactions.ResultsTNF-α-857 C/T containing the T allele was significantly associated with an increased risk of gastric cancer and a linear trend effect was observed in the additive model (OR = 1.6, 95% CI 1.0–2.5 for CT genotype; OR = 2.6, 95% CI 1.0–6.4 for TT genotype). All haplotype-pairs that contained TCT or CCC of TNF-α-1031 T/C, TNF-α-863 C/A, and TNF-α-857 C/T were associated with a significantly higher risk for gastric cancer only among smokers. In the MDR analysis, regardless of smoking status, TNF-α-857 C/T was included in the first list of SNPs with a significant main effect.ConclusionTNF-α-857 C/T polymorphism may play an independent role in gastric carcinogenesis and the risk for gastric cancer by TNF genetic effect is pronounced by cigarette smoking.

Intake of Soy Products and Other Foods and Gastric Cancer Risk: A Prospective Study

Background Gastric cancer, the most common cancer in the world, is affected by some foods or food groups. We examined the relationship between dietary intake and stomach cancer risk in the Korean Multi-Center Cancer Cohort (KMCC). Methods The KMCC included 19 688 Korean men and women who were enrolled from 1993 to 2004. Of those subjects, 9724 completed a brief 14-food frequency questionnaire at baseline. Through record linkage with the Korean Central Cancer Registry and National Death Certificate databases, we documented 166 gastric cancer cases as of December 31, 2008. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% CIs. Results Frequent intake of soybean/tofu was significantly associated with reduced risk of gastric cancer, after adjustment for age, sex, cigarette smoking, body mass index, alcohol consumption, and area of residence (P for trend = 0.036). We found a significant inverse association between soybean/tofu intake and gastric cancer risk among women (RR = 0.41, 95% CI: 0.22–0.78). Men with a high soybean/tofu intake had a lower risk of gastric cancer, but the reduction was not statistically significant (RR = 0.77, 95% CI: 0.52–1.13). There was no interaction between soybean/tofu intake and cigarette smoking in relation to gastric cancer risk (P for interaction = 0.268). Conclusions Frequent soybean/tofu intake was associated with lower risk of gastric cancer.

A Prospective Study Investigating the Association Between Environmental Tobacco Smoke Exposure and the Incidence of Type 2 Diabetes in Never Smokers

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.

Isoflavones: chemistry, analysis, functions and effects on health and cancer.

Isoflavones are phytoestrogens and natural plant compounds which are similar to 17-β-estradiol in chemical structure. It is known that they can act as estrogen agonists or antagonists, depending on endocrine estrogenic levels, but actions of isoflavones are rather complex due to large number of variables such as chemical structures and mechanisms. Some hypotheses on biological mechanisms have not satisfactorily been confirmed to date and human epidemiological and experimental studies have been relatively limited. Nevertheless, isoflavones and isoflavone rich foods have become a focus on interest due to positive health benefits on many diseases, especially prevention of hormone-related cancers, cardiovascular disease, osteoporosis, and adverse postmenopausal symptoms, and improvement of physiological condition such as maintaining cognitive function. This review provides an overview of chemistry, analytical techniques (focused on human biospecimens), functions including biological mechanisms, and effects of isoflavones, on the basis of the available meta-analysis and review articles and some original articles, on health and cancer.

Rice-eating pattern and the risk of metabolic syndrome especially waist circumference in Korean Genome and Epidemiology Study (KoGES)

BackgroundMetabolic syndrome poses a serious health threat in Asian countries. Rice is a staple food in Korea, and carbohydrate intake is associated with the risk of MetS. We hypothesized that various rice-eating patterns in a carbohydrate-based diet would have different effects on the risk of MetS.MethodsParticipants were 26,006 subjects enrolled in the Korean Genome and Epidemiology Study between 2004 and 2006. They were classified into four dietary patterns - white rice, rice with beans, rice with multi-grains, and mixed based on their food frequency questionnaire responses. We compared metabolic risk traits according to the rice-eating patterns.ResultsNutrients consumption and the presence of MetS risk factors differed according to rice-eating patterns. In men odds ratio(OR) for central obesity was slightly elevated in mixed group(1.18). In women, the risk for central obesity and abnormal fasting glucose were lower in the rice with beans group (adjusted OR =0.79, 0.83 respectively) and central obesity in rice with multi-grains(adjusted OR=0.91) than the white rice group. In postmenopausal women, ORs for central obesity (0.78) and abnormal fasting glucose (0.75) in the rice with beans group and ORs for central obesity (0.83), abnormal HDL-cholesterol (0.87) and MetS(0.85) in the rice with multi-grains group was lower than those in white rice group. In premenopausal women, the risk for central obesity (OR=0.77) was reduced in the rice with beans group.ConclusionThe risk for MetS was lower in the rice with beans and rice with multi-grains groups compared with the white rice group, particularly in postmenopausal women.

Viral Hepatitis and Liver Cancer in Korea: an Epidemiological Perspective

In the past, hepatitis B virus (HBV) infection was endemic in the general Korean population. The association of HBV infection with the occurrence of liver cancer has been well demonstrated in several epidemiologic studies. While the mortality rates of liver cancer in Korea have decreased steadily over the last decade, the presence of hepatitis B surface antigen (HBsAg) in mothers remains high at 3-4%, and 25.5% of these HBsAg positive mothers are positive for hepatitis B e antigen (HBeAg). HBV infection caused almost a quarter of hepatocellular carcinoma (HCC) cases and one-third of deaths from HCC. These aspects of HBV infection prompted the Korean government to create a vaccination program against HBV in the early 1980s. In 1995, the Communicable Disease Prevention Act (CDPA) was reformed, and the government increased the number of HBV vaccines in the National Immunization Program (NIP), driving the vaccination rate up to 95%. In 2000, the National Health Insurance Act (NHIA) was enacted, which provided increased resources for the prevention of perinatal HBV infection. Then in 2002, the Korean government, in conjunction with the Korean Medical Association (KMA), launched an HBV perinatal transmission prevention program. The prevalence of HBsAg in children had been high (4-5%) in the early 1980s, but had dropped to below 1% in 1995, and finally reached 0.2% in 2006 after the NIP had been implemented. After the success of the NIP, Korea finally obtained its first certification of achievement from the Western Pacific Regional Office of the World Health Organization (WPRO-WHO) for reaching its goal for HBV control. An age-period-cohort analysis showed a significant reduction in the liver cancer mortality rate in children and adolescents after the NIP had been implemented. In addition to its vaccination efforts, Korea launched the National Cancer Screening Program (NCSP) for 5 leading sites of cancer, including the liver, in 1999. As a consequence of this program, the 5-year liver cancer survival rate increased from 13.2% (1996-2000) to 23.3% (2003-2008). The development of both the primary and secondary prevention for liver cancer including HBV immunization and cancer screening has been of critical importance.

Prospective Study of Optimal Obesity Index Cutoffs for Predicting Development of Multiple Metabolic Risk Factors: The Korean Genome and Epidemiology Study

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/m2 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.

Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: results from the Korean Genome and Epidemiology Study

Aims/hypothesisTo 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.MethodsThe 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.ResultsIn 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/interpretationHigh 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.