Coffee and tea consumption and mortality from all causes, cardiovascular disease and cancer: a pooled analysis of prospective studies from the Asia Cohort Consortium.

BACKGROUND: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. METHODS: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. RESULTS: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. CONCLUSIONS: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

Plasma phytoestrogens concentration and risk of colorectal cancer in two different Asian populations.

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.

Determinants of gastric cancer screening attendance in Korea: a multi-level analysis.

BACKGROUND: We aimed to assess individual and area-level determinants of gastric cancer screening participation. METHOD: Data on gastric cancer screening and individual-level characteristics were obtained from the 2007-2009 Fourth Korea National Health and Nutrition Examination Survey. The area-level variables were collected from the 2005 National Population Census, 2008 Korea Medical Association, and 2010 National Health Insurance Corporation. The data were analyzed using multilevel logistic regression models. RESULTS: The estimated participation rate in gastric cancer screening adhered to the Korea National Cancer Screening Program guidelines was 44.0% among 10,658 individuals aged over 40 years who were included in the analysis. Among the individual-level variables, the highest income quartile, a college or higher education level, living with spouse, having a private health insurance, limited general activity, previous history of gastric or duodenal ulcer, and not currently smoking were associated with a higher participation rate in gastric cancer screening. Urbanization showed a significant negative association with gastric cancer screening attendance among the area-level factors (odds ratio (OR) = 0.73; 95% confidence interval (CI) = 0.57-0.93 for the most urbanized quartile vs. least urbanized quartile). CONCLUSION: There are differences in gastric cancer screening attendance according to both individual and regional area characteristics.

Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.

BACKGROUND: The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. METHODS: Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. RESULTS: In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01). CONCLUSIONS: Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

Interaction effects between genes involved in the AKT signaling pathway and phytoestrogens in gastric carcinogenesis: a nested case-control study from the Korean Multi-Center Cancer Cohort.

SCOPE: To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene-environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer. METHODS AND RESULTS: The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case-control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66-0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03-1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03-1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (p(interaction) < 0.05). CONCLUSION: CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.

Genetic susceptibility on CagA-interacting molecules and gene-environment interaction with phytoestrogens: a putative risk factor for gastric cancer.

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.

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.

Soybean product intake modifies the association between interleukin-10 genetic polymorphisms and gastric cancer risk.

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.

Cancer control activities in the Republic of Korea.

South Korea has a population of 47.3 million. The whole population is covered by a mandatory social insurance system (the National Health Insurance Program) that is financed through the contributions paid by the insured and their employers. Cancer has been the leading cause of death in Korea since 1983. About 130 000 people develop cancer annually with 66 000 deaths in 2006. Cancer patients' 5-year survival rates between 1998 and 2002 were 37.8 and 57.0% for men and women, respectively. The five leading primary cancer sites were stomach, lung, liver, colon and rectum, and bladder among males, whereas the most common cancers were stomach, breast, colon and rectum, uterine cervix and lung among females. With the rapidly aging population, reducing cancer burden at the national level has become one of the major political issues in Korea. The government formulated its first 10-year plan for cancer control in 1996. In 2000, the National Cancer Center was created and the Cancer Control Division was set up within the Ministry of Health and Welfare. The Cancer Control Act was legislated in 2003. Korea's major national cancer control programs are anti-smoking campaigns, hepatitis B virus vaccination, cancer registration and networking, promotion of R&D activities for cancer control, education and training for cancer control and prevention, operation of the national cancer information center, operation of the mass screening program for five common cancers, management of cancer patients at home, financial support for cancer patients and designation of regional cancer centers.

Prediagnosis smoking, obesity, insulin resistance, and second primary cancer risk in male cancer survivors: National Health Insurance Corporation Study.

PURPOSE: Smoking, obesity, and insulin resistance are well-known risk factors for cancer, yet few epidemiology studies evaluate their role as risk factors for a second primary cancer (SPC). PATIENTS AND METHODS: We identified 14,181 men with a first cancer from the National Health Insurance Corporation Study cohort. We obtained data on fasting glucose level, body mass index (BMI), and smoking history from an enrollment interview (1996). We obtained SPC incidence data for 1996 through 2002 from the Korean Central Cancer Registry. We used the standard Poisson regression model to estimate the age- and multivariate-adjusted relative risk (RR) for SPCs in relation to smoking history, BMI, and insulin resistance before diagnosis. RESULTS: We observed 204 patients with SPC. The overall age-standardized incidence rate of SPC was 603.2 occurrences per 100,000 person-years, which was about 2.3 times higher than that of first cancer in the general male population. Multivariate regression revealed that lung (RR, 3.69; 95% CI, 1.35 to 10.09) and smoking-related (RR, 2.02; 95% CI, 1.02 to 4.03) SPCs were significantly associated with smoking. Obese patients (BMI > or = 25 kg/m2) had significantly elevated RRs for colorectal (RR, 3.45; 95% CI, 1.50 to 7.93) and genitourinary (RR, 3.61; 95% CI, 1.36 to 9.54) SPCs. Patients with a fasting serum glucose concentration > or = 126 mg/dL had a higher RR for hepatopancreatobiliary (RR, 3.33; 95% CI, 1.33 to 8.37) and smoking-related (1.93; 95% CI, 1.01 to 3.68) SPCs. CONCLUSION: Prediagnosis smoking history, obesity, and insulin resistance were risk factors for several SPCs. These findings suggest that more thorough surveillance and screening for SPCs is needed for the cancer survivors with these risk factors.

Dose-specific or dose-dependent effect of growth hormone treatment on the proliferation and differentiation of cultured neuronal cells.

OBJECTIVE: GH controls the proliferation of cartilage, fibroblasts or the differentiation of adipose and muscle tissue. However, the effect of GH on neuronal cells remains unknown. The present study was conducted to determine the proliferative or differentiating effect of GH on the nervous system in vitro. DESIGN: Neuronal hybrid cells (VSC4.1) were cultured with GH. The concentration ranged from 0.134 microg/ml up to 1.34 mg/ml. A cell confluency and MTT assay, cell cycle phase analysis with flow cytometry, extracellular receptor kinase (ERK) phosphorylation and mitogen activated protein kinase (MAPK) inhibitor (PD98050) assays were all performed to determine the effect on proliferation. Differentiation was evaluated by neurite outgrowth and neurofilament expression. Terminally differentiated neurons were stained by Hoechst 33342 for apoptotic nuclear fragmentation by degeneration. Poly-adenosyl ribose polymerase (PARP) expression and its cleavage products were evaluated. RESULTS: Cells at concentrations between 0.134 microg/ml and 1.34 microg/ml of GH proliferated with ERK phosphorylation, which was attenuated by MAPK inhibitors. Proliferation decreased at concentrations higher than 13.4 microg/ml; however, neurite outgrowth was observed at these concentrations. Terminally differentiated cells underwent apoptosis and showed nuclear fragmentation by Hoechst 33342 staining. PARP expression was increased with caspase-3 dependent-cleaved fragment. CONCLUSIONS: Our in vitro data demonstrate that GH exerts dual effects; proliferation with a specific GH dose window, or differentiation in a dose-dependent manner in cultured neuronal hybrid cells.