Tsu-Nai Wang

Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan

A multicenter case‐control study was conducted in northern and southern Taiwan to clarify the independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer. A total of 513 patients with newly diagnosed and histopathologically confirmed squamous cell carcinoma of the esophagus and 818 gender, age and study hospital‐matched controls were included. We found a significant dose‐response relationship between the duration and intensity of consumption of the 3 substances and the development of this neoplasm in this site. Although the amount of alcohol consumed had a stronger effect on the risk of esophageal cancer than the number of years it was consumed, however, the number of years one smoked had a stronger effect on the risk than the amount of cigarettes consumed. The strongest risk factor of esophageal cancer was alcohol intake, with highest risk (OR = 13.9) being for those who consumed more than 900 g/day‐year. Combined exposure to any 2 of 3 substances brought the risks up to 8.8–19.7 fold and, to all 3 substances, to 41.2‐fold. A multiplicative interaction effect for alcohol drinkers who smoked on cancer risk was detected, whereas an additive interaction effect was found among drinkers who chewed. The combined effect of all 3 substances accounted for 83.7% of the attributable fraction of contracting esophageal cancer in this population. In conclusion, these results suggest that the intensity and the length of time alcohol and tobacco are used play different roles in the etiology of esophageal cancer. Alcohol separately interacts with tobacco and betel quid in a differently synergistic way in determining the development of this site of cancer.

G-2548A Polymorphism of the Leptin Gene Is Correlated with Extreme Obesity in Taiwanese Aborigines

We examined the genetic associations of the G‐2548A polymorphism in the promoter of the leptin (LEP) gene and the Gln223Arg (Q223R) polymorphism of the leptin receptor (LEPR) gene with obesity. Two hundred twenty‐six obese aboriginal subjects (BMI ≥ 27 kg/m2) and 182 aboriginal subjects with normal weight (BMI < 25 kg/m2) participated in this study. The polymorphisms of LEP G‐2548A and LEPR Q223R were genotyped by polymerase chain reaction/restriction fragment length polymorphism, and their anthropometric characteristics were measured. Levels of leptin, triglycerides, and cholesterol were measured after overnight fasting. We found that the frequencies of the LEP G/G homozygote (22.6%) with Mendelian recessive (χ2 = 7.89, p = 0.005) and codominant (χ2 = 7.93, p = 0.02) models to be higher in the extremely obese subjects (BMI ≥ 35 kg/m2) than in normal weight subjects (6.9%) but not in moderately obese subjects (35 > BMI ≥ 27 kg/m2). There was no difference in genotypic frequency of the LEPR Q223R polymorphism between the extreme obese and control groups. We suggest that the LEP −2548 G/G homozygote plays a genetic recessive role in the development of extreme obesity in Taiwanese aborigines.

Extreme BMI predicts higher asthma prevalence and is associated with lung function impairment in school-aged children†

The prevalence of obesity and asthma has increased in recent decades. We investigated the relationship between body mass index (BMI) and lung function, and also tried to determine if asthma prevalence differs between obese and non‐obese children.

Asthma and Suicide Mortality in Young People: A 12-Year Follow-Up Study

OBJECTIVE Mortality risk is relatively high in young people with asthma, and the risk may include causes of death other than those directly linked to respiratory disease. The authors investigated the association between asthma and suicide mortality in a large population-based cohort of young people. METHOD A total of 162,766 high school students 11 to 16 years of age living in a catchment area in Taiwan from October 1995 to June 1996 were enrolled in a study of asthma and allergy. Each student and his or her parents completed structured questionnaires. Participants were classified into three groups at baseline: current asthma (symptoms present in the past year), previous asthma (history of asthma but no symptoms in the past year), and no asthma. Participants were followed to December 2007 by record linkage to the national Death Certification System. Cox proportional hazards models were used to study the association between asthma and cause of death. RESULTS The incidence rate of suicide mortality in participants with current asthma at baseline was more than twice that of those without asthma (11.0 compared with 4.3 per 100,000 person-years), but there was no significant difference in the incidence of natural deaths. The adjusted hazard ratio for suicide was 2.26 (95% CI=1.43-3.58) in the current asthma group and 1.76 (95% CI=0.90-3.43) in the previous asthma group. Having a greater number of asthma symptoms at baseline was associated with a higher risk of subsequent suicide. The population attributable fraction was 7.0%. CONCLUSIONS These results highlight evidence of excess suicide mortality in young people with asthma. There is a need to improve mental health care for young people, particularly those with more severe and persistent asthma symptoms.

Genomewide Scan for Gout in Taiwanese Aborigines Reveals Linkage to Chromosome 4q25

Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population, including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout, which suggests a founder effect across the Pacific region. We report here a genomewide linkage study of 21 multiplex pedigrees with gout from an aboriginal tribe in Taiwan. From observations of familial clustering, early onset of gout, and clinically severe manifestations, we hypothesized that a major gene plays a role in this trait. Using 382 random polymorphic markers spread across 22 autosomes, we demonstrated a highly significant linkage for gout at marker D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPL(all) statistic]; empirical P=.0006; LOD=4.3, P=4.4x10-6 by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P=1.3x10-6). Quantitative traits, including serum uric acid and creatinine, also showed a moderate linkage to this region. To our knowledge, this is the first genome-scan report to identify a genetic locus harboring a gout-susceptibility gene.

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.

Risks of Exposure to Occupational Asthmogens in Atopic and Nonatopic Asthma: A Case-Control Study in Taiwan

RATIONALE Asthma is often work-related and can be classified as atopic or nonatopic on the basis of its pathogenesis. Few studies have reported an association between exposure to occupational asthmogens and asthma with and without atopy. OBJECTIVES We investigated, in adults with asthma, whether occupational exposure to asthmogens influenced the risk of having atopic or nonatopic asthma, and their level of lung function. METHODS We recruited 504 hospital-based adults with current asthma, 504 community-based control subjects, and 504 hospital-based control subjects in southern Taiwan. Asthma with atopy was defined as having asthma in combination with an increase in total IgE (≥100 U/ml) or a positive Phadiatop test (≥0.35 Pharmacia arbitrary unit/L) (Pharmacia ImmunoCAP; Pharmacia, Uppsala, Sweden). Occupational exposure to asthmogens was assessed with an asthma-specific job exposure matrix. MEASUREMENTS AND MAIN RESULTS We found a significant association between atopic asthma and exposure to high molecular weight asthmogens (adjusted odds ratio [AOR], 4.0; 95% confidence interval [CI], 1.8-8.9). Nonatopic asthma was significantly associated with exposure to low molecular weight asthmogens (AOR, 2.6; 95% CI, 1.6-4.3), including industrial cleaning agents and metal sensitizers. Agriculture was associated with both atopic and nonatopic asthma (AOR, 7.8; 95% CI, 2.8-21.8; and AOR, 4.1; 95% CI, 1.3-13.0, respectively). The ratio of FEV₁ to FVC in the high-risk group was significantly lower than in the no-risk group (P = 0.026) in currently employed patients with asthma. CONCLUSIONS In adults with asthma, occupational exposure to high and low molecular weight asthmogens appears to produce differential risks for atopic and nonatopic asthma.

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.

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis.

Genetic variants in alcohol dehydrogenase‐1B (ADH1B) and aldehyde dehydrogenase‐2 (ALDH2) genes modulate acetaldehyde removal upon alcohol ingestion. Although these genetic vulnerabilities have been linked to higher esophageal squamous cell carcinoma (ESCC) risks, it is unclear whether they also determine the time of malignancy presentation. The purpose of this investigation was to unravel genotoxic effects of the two alcohol‐metabolizing genes with regard to alcohol and tobacco consumption on the age at ESCC diagnosis and tumor dissemination. ADH1B/ALDH2 genotyping was performed on lymphocyte DNA specimens taken from 406 consecutively registered incident patients with pathology‐proven ESCC. To fully utilize individual genetic and survival information, survival analyses and gene‐longevity applied approaches were introduced. Among heavy drinkers, the ADH1B Arg/Arg (55 years) and ALDH2 Glu/Lys genotypes (54 years) were found to confer a 15 and 16 years earlier carcinoma diagnosed age than His/His and Glu/Glu nondrinkers (both 70 years), respectively. For drinkers, 1‐year age advancement was, separately, associated with a 0.977 and 0.953‐fold stepwise reduced likelihood of being ADH1B Arg homozygote and ALDH2 Lys variant. Noticeably elevated hazard‐ratio (HR) for drinkers of ADH1B slow‐form genotype and ALDH2 inactive‐form allele were identified in smokers (HR = 2.3–2.6), but no in nonsmokers. In smokers, appreciably higher cumulative cancer onset risks were correspondingly recognized from the age of 45 and 49 upward among any + Lys allele and Arg/Arg + Glu/Glu combined‐ADH1B/ALDH2‐genotype drinkers than nondrinkers. In conclusion, consumption of tobacco and alcohol, coupled with genetic susceptibilities associated with acetaldehyde elimination, as modulated by ADH1B and ALDH2 genotypes, determines a substantial magnitude of tumorigenetic effect on earlier age ESCC diagnosis.

UCP2 A55V variant is associated with obesity and related phenotypes in an aboriginal community in Taiwan

Objective:Human uncoupling proteins 2 and 3 (UCP2 and UCP3) are two mitochondrial proteins that are involved in the control of metabolism of fatty acid and possibly protect against oxidative damage. The aim of this study was to analyze genetic associations of four polymorphisms of the UCP2 and UCP3 genes with insulin, leptin concentration and obesity in Taiwan aborigines.Research methods:Four polymorphisms were compared in 324 obese (body mass index (BMI) ⩾30 kg/m2) and overweight (30>BMI ⩾25 kg/m2) subjects, and 114 normal weight subjects (BMI <25 kg/m2) in an aboriginal community of southern Taiwan. Anthropometric characteristics and fasting levels of insulin, leptin, triglycerides and cholesterol were measured.Results:Before and after adjusting for age distribution, only the Val55 allele in exon 4 of the UCP2 gene increased the risk of overweight and obesity (adjusted odds ratio (OR)=2.02, P=0.004) in comparison with Ala55. UCP2 V55V is also associated with higher fasting insulin levels than A55V (P=0.01) and A55A (P=0.04) in the obese/overweight group. Using the COCAPHASE program of the UNPHASED software, haplotype analysis of three single nucleotide polymorphisms (A55V-G866A-C-55T) revealed that A-G-C (73% in obese subjects and 77% in controls) was the most common haplotype and that the haplotype V-A-T (13% in obese subjects and 5% in controls) was significantly increased in obese and overweight subjects (BMI ⩾25 kg/m2) (OR=2.62, P<0.001).Discussions:UCP2 A55V variant might predispose to obesity and Val55 allele to confer population-attributable risk for 9.5% of obese disorders and increase insulin concentrations. The V-A-T haplotype within UCP2-UCP3 gene cluster is also significantly associated with obesity in Paiwan aborigines.