Chun-Ying Lee

Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid

The consumption of alcohol, tobacco and betel quid has been found to be an important contributor to esophageal squamous cell carcinoma (ESCC) in Taiwan. The genotoxic effect of the ADH1B and ALDH2 genes modulating an individuals alcohol‐metabolizing capacity on ESCC may be linked to drinking behavior, intake pattern and other exogenous factors. To investigate the interplay of these genetic and environmental factors in determining the risk of ESCC, a multicenter case‐control study was conducted. Here, 406 patients with pathology‐proven ESCC, as well as 656 gender, age and study hospital matched controls were recruited. Genetic polymorphisms of ADH1B and ALDH2 appeared to correlate with the abstinence of alcohol, though not with tobacco and betel quid. Within the same levels of alcohol consumption, carcinoma risks increased along with an increase in the numbers of ADH1B*1 and ALDH2*2 alleles. The inactive ALDH2*1/*2 genotype was found to multiplicatively interact with a low‐to‐moderate (0.1–30 g/day) and a heavy (>30 g/day) ethanol intake to increase the ESCC risk (the joint aOR = 14.5 and 102.6, respectively). Among low‐to‐moderate drinkers, a smoking‐dependent carcinogenetic effect for the ADH1B*1/*1 and ALDH2*1/*2+*2/*2 genotypes was recognized, with significant risks found in smokers, but not in nonsmokers. Further, a supra‐multiplicative combined risk of ESCC for alcohol and tobacco use was identified among carriers of the ADH1B*1/*1 genotype (p for interaction = 0.042). In conclusion, the interplay of the ADH1B and ALDH2 genotypes, in conjunction with a behaved drinking habit and a practiced drinking pattern, along with continued tobacco consumption, plays an important pathogenic role in modulating ESCC risk.

Consumption of Sugar-Sweetened Beverages Is Associated with Components of the Metabolic Syndrome in Adolescents

Sugar-sweetened beverages (SSBs) are the principle source of added sugar in diets. Cardiometabolic disturbances can occur from early childhood to adulthood. The aim of this cross-sectional study was to examine the gender-specific association of SSB intake with metabolic syndrome (MetS) and its components among adolescents in Taiwan. A total of 2727 adolescents aged 12 to 16 years randomly selected from three diverse economic areas in Southern Taiwan by using a multistage-sampling strategy participated in this study. Demographic, dietary, physical and anthropometric parameters were measured, and serum lipid profiles and glucose levels were determined. The International Diabetes Federation (IDF) specifies that MetS requires abdominal obesity and ≥2 abnormal components, and Cook criteria for MetS require ≥3 abnormal components. We applied survey-data modules to data analyses, and used multiple regression and logistic models to adjust for covariates. An increased SSB intake was linked to a greater waist circumference in both sexes and to systolic blood pressure in boys (P for trend: ≤0.043). Male moderate and high consuming SSB drinkers exhibited triglyceride levels that were 8.0 and 8.2 mg/dL significantly higher, respectively, than those of nondrinkers. Compared with nondrinkers, boys who consumed >500 mL/day (high quantity) of SSBs exhibited 10.3-fold (95% confidence intervals (CIs): 1.2-90.2) and 5.1-fold (95% CIs: 1.01-25.5) risks of contracting MetS, as defined by the IDF and Cook criteria for MetS, respectively. In girls, the risk estimates for the same comparison were not significant by the IDF criteria (6.5-fold risk, 95% CIs: 0.9-∞) or Cook criteria (5.9-fold risk, 95% CIs: 0.8-43.8) for MetS. High SSB consumption was also linked to 1.9-fold (95% CIs: 1.1-3.1) and 2.7-fold (95% CIs: 1.3-5.7) higher risks of being at a greater overall metabolic risk in girls and boys, respectively. In conclusion, a high SSB intake is associated with adolescent MetS among boys but not girls in Taiwan.

Effects on uric acid, body mass index and blood pressure in adolescents of consuming beverages sweetened with high-fructose corn syrup.

Objective:The dietary intake of fructose-rich sugar-sweetened beverages (SSB) may have a significant role in raising serum uric acid (SUA) levels as well as the risk of contracting gout and cardiovascular risk factors. Our objective was to investigate the impact of SSB intake on SUA, body mass index (BMI) and systolic blood pressure (SBP) among adolescents in Taiwan.Methods:We evaluated data from 2727 representative adolescents who were multistage sampled from 36 Junior High schools in Taiwan. We cross-sectionally collected demographic, physical, dietary and anthropometric variables, and prospectively measured clinical outcomes. Data were analyzed using multiple regression and logistic models adjusted for covariates.Results:We found that 87.7% of adolescents were SSB drinkers, with 25.1% drinking >500 ml per day of such beverages. Increased SSB intake was associated with increased waist and hip circumferences, body fat, BMI, SBP and SUA. As compared with non-drinkers, SSB drinkers had a 3.2–4.9 elevated risk of obesity. The prevalence of hyperuricemia in heavy SSB users (40.2–49.4%) was appreciably greater than that for non-users (24.2%). Adolescents who consumed >500 ml per day of heavy high-fructose corn syrup (HFCS) containing beverages had a 0.42 mg dl−1 higher SUA level and a 2.0–2.1 increased risk of developing hyperuricemia than non-drinkers. The consumption of HFCS-rich beverages was also found to interact with obesity in determining higher levels of SUA (2.2–2.4 mg dl−1 increases).Conclusion:High SSB consumption has a notable effect on increased levels of BMI and SUA. The intake of HFCS-rich beverages and BMI were likely to interactively strengthen SUA levels among obese adolescents.

Food intake and the occurrence of squamous cell carcinoma in different sections of the esophagus in Taiwanese men.

OBJECTIVE The main objective of this study was to further elucidate the effect of consuming various foods on the development of squamous cell carcinoma (SCC) in three different sections of the esophagus. METHODS A total of 343 patients with SCC of the esophagus and 755 cancer-free control subjects were recruited for this study from 1996 to 2005. RESULTS We found that intake of vegetables, raw onions/garlic, and fruits are significantly protective against esophageal SSC risk, whereas intake of hot foods can significantly increase its risk. There was a significant inverse relation between the frequency of tea consumption and esophageal SCC risk (P for trend = 0.005), with a 0.5-fold lower risk associated with the intake of unfermented tea (green tea, oolong tea, or jasmine tea). The effects of dietary factors on esophageal SCC were similar in all subsites, with the exception of consumption of coffee. Coffee consumption was more pronounced in having a protective effect in the middle third section compared with the lower third section of the esophagus (adjusted odds ratio 0.4, 95% confidence interval 0.2-0.9), although this protective effect was marginally significant (adjusted odds ratio 0.6, 95% confidence interval 0.4-1.0) against esophageal SCC in all subsites. Our data also suggest that discomfort when eating hot foods may exert a carcinogenic effect by direct contact with the esophageal mucosa and tend to have more harmful effects in the upper than in the lower esophagus. In contrast, vegetables, fruits, and tea with components that are thought to inhibit carcinogenesis by absorbed components affected all subsites similarly. CONCLUSION Our results add additional information that certain dietary components may affect carcinogenesis locally and systemically.

Fructose-Rich Beverage Intake and Central Adiposity, Uric Acid, and Pediatric Insulin Resistance

OBJECTIVE To determine the association between sugar-sweetened beverage (SSB) consumption with biomarkers of insulin resistance (IR) and investigate whether/how this relates to obesity and serum uric acid in adolescents. STUDY DESIGN Adolescents (n = 1454, aged 12-16 years) were assessed in a study conducted to monitor Multilevel Risk Profiles for Adolescent Metabolic Syndrome in Taiwan. Detailed information about demographics, diet, physical, anthropometric, and clinical variables was collected. An original homeostatic model assessment of IR (HOMA1-IR), updated nonlinear homeostatic model assessment of IR (HOMA2-IR) model, and several IR markers were measured. RESULTS Adolescents who consumed a greater amount of SSBs were more likely to have elevated fasting serum insulin, HOMA1-IR, and HOMA2-IR (P for trends, ≤.028). Compared with SSB nondrinkers, those with >350 mL/d intake of heavy high-fructose corn syrup-containing SSBs had a 0.52 and 0.30 higher multivariate-adjusted HOMA1-IR and HOMA2-IR, respectively. Waist circumference and serum uric acid were correspondingly found to explain 25.4% and 23.6%, as well as 23.2% and 20.6%, of the increases in the 2 IR markers. Both the elevations of HOMA1-IR and HOMA2-IR for high-fructose corn syrup-rich SSB intake were strengthened among obese adolescents (P for interaction, ≤.033). CONCLUSIONS Fructose-rich SSB intake is associated with elevated levels of IR, and this relationship may be partially mediated by central adiposity and serum uric acid. Obesity may modify the effect of this type of SSB consumption in intensifying the elevation of IR in adolescents.

Elevated Serum Triglyceride and Retinol-Binding Protein 4 Levels Associated with Fructose-Sweetened Beverages in Adolescents

Background The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production. Objectives This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. Methods We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. Results Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (≥24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r = 0.253 to 0.404), but not among non-drinkers. Conclusions High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4.

Association Between Serum Leptin and Adiponectin Levels with Risk of Insulin Resistance and Impaired Glucose Tolerance in Non-diabetic Women

Obesity is a well known risk factor for insulin resistance and type 2 diabetes. Recently discovered adipocyte‐derived proteins (leptin and adiponectin) might contribute to the pathologic mechanism linking obesity and insulin resistance. A total of 190 non‐diabetic women were recruited from the Obesity Clinic of Kaohsiung Municipal Hsiao‐Kang Hospital, Taiwan, between February 2003 and February 2004. All participants completed a simple questionnaire. Blood pressure and body mass index were measured; blood samples for fasting glucose, total cholesterol, high‐density lipoprotein cholesterol, triglyceride, leptin, adiponectin, and fasting insulin level were collected after an overnight fast. Two‐hour glucose level after a 75‐g glucose tolerance test was determined. Homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated as the index of insulin resistance. Multivariate linear regression analyses were used to analyze the relationship between adipocytokines and insulin resistance after adjusting for possible confounding factors. Leptin and adiponectin were found to be independently associated with HOMA‐IR and fasting insulin concentration, but in divergent directions, after adjusting for potential confounding factors. Adiponectin, but not leptin, was associated with impaired glucose tolerance after adjusting for potential confounding factors. The results suggest that leptin and adiponectin may be involved in the pathophysiologic link between obesity and insulin resistance independently. Low levels of adiponectin may increase the risks of developing impaired glucose metabolism and type 2 diabetes.

Association of Parental Overweight and Cardiometabolic Diseases and Pediatric Adiposity and Lifestyle Factors with Cardiovascular Risk Factor Clustering in Adolescents

Cardiometabolic risk factors or their precursors are observed in childhood and may continue into adulthood. We investigated the effects of parental overweight and cardiometabolic diseases and pediatric lifestyle factors on the clustering of cardiovascular risk factors among adolescents, and examined the mediating and modifying effects of pediatric adiposity on these associations. Representative adolescents (n = 2727; age, 12–16 years) were randomly recruited through multistage stratified sampling from 36 schools in Southern Taiwan. Adolescent and parent surveys were conducted in schools and participant homes, respectively. Their demographic factors, diet patterns, and physical, anthropometric, and clinical parameters were collected and analyzed. Adolescents with 1–2 and ≥3 risk components for pediatric metabolic syndrome (MetS) were defined as potential MetS (pot-MetS) and MetS, respectively. Adolescents whose parents were overweight/obese, or with diabetes and hypertension had a higher prevalence ratio of pot-MetS and MetS (1.5–1.6 and 1.9–4.2-fold, respectively). Low physical activity (<952.4 MET·min/week), long screen time (≥3 h/day) and high sugar-sweetened beverage intake (>500 mL/day) were associated with a 3.3- (95% confidence intervals (CI) = 1.5–7.3), 2.2- (95% CI = 1.1–4.4), and 26.9-fold (95% CI = 3.2–229.0) odds ratio (OR) of MetS, respectively. Pediatric body mass index (BMI) accounted for 18.8%–95.6% and 16.9%–60.3% increased prevalence ratios of these parental and pediatric risk factors for MetS. The OR of pot-MetS + MetS for sugar-sweetened beverage consumption was multiplicatively enhanced among adolescents with overweight/obesity (combined OR, 8.6-fold (95% CI = 4.3–17.3); p for multiplicative interaction, 0.009). The results suggest that parental overweight and cardiometabolic diseases and pediatric sedentary and high sugar-intake lifestyles correlate with the development of adolescent MetS, and an elevated child BMI explains a part of these associations. Pediatric adiposity might be multiplicatively associated with sugar-sweetened beverage consumption for enhancing the MetS prevalence ratio among adolescents.

Combined effect of C-reactive protein gene SNP + 2147 A/G and interleukin-6 receptor gene SNP rs2229238 C/T on anthropometric characteristics among school children in Taiwan

Objective:The purpose of this study was to explore the combined effect of the C-reactive protein (CRP) +2147 A/G (rs1205) and interleukin (IL)-6R rs2229238 C/T single-nucleotide polymorphisms (SNPs) on the anthropometric variables of school children in Taiwan.Subjects and Design:Cross-sectional analyses were performed using the data from the Taipei Children Heart Study-II. After multi-stage sampling, we selected 430 boys and 463 girls with an average age of 13.1 years. We genotyped these individuals for the CRP +2147 A/G and IL-6R rs2229238 C/T SNPs using a TaqMan 5′ nuclease assay. Anthropometric characteristics, which included body height, body weight (BW), body mass index (BMI), waist circumference (WC), hip circumference (HC), body fat percentage (BF), and waist circumference to height ratio (WHtR), were measured/calculated.Results:When considering the CRP +2147 A/G polymorphism, GG genotype boys were heavier and had larger BMI, WC, HC, BF and WHtR than A allele carriers. The odds ratio (OR) of larger WHtR in GG genotype boys was 2.14 (95% CI: 1.09–4.21). For the IL-6R rs2229238 C/T polymorphism, T allele carrier girls had larger WC and WHtR than those carrying the CC genotype. The OR of a larger HC for T allele carrier boys was 2.33 (95% CI: 1.16–4.68). Boys with the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T had higher OR for BW, BMI, WC, HC, BF and WHtR than boys who were carriers of the A allele of CRP +2147 A/G and had the CC genotype of IL-6R rs2229238 C/T (OR range=3.86–8.04, all P<0.05).Conclusion:Boys who carry the GG genotype of CRP +2147 A/G and the CC genotype of IL-6R rs2229238 C/T have a greater risk of having abnormal BW, BMI, WC, HC, BF and WHtR and of developing obesity than individuals who do not have these genotypes.

Apoptotic effect of Helicobacter pylori on oesophageal squamous-cell carcinoma cells in vitro.

Backbround  The relationship between Helicobacter pylori (Hp) infection and oesophageal squamous‐cell carcinoma (ESCC) risk is still inconclusive. Our previous study found an inverse association between the two, but its mechanism is still unknown. Thus, we conducted in vitro studies to clarify the issue.