Hsiao-Ling Huang

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.

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.

Anatomical subsite discrepancy in relation to the impact of the consumption of alcohol, tobacco and betel quid on esophageal cancer

The carcinogenetic impact of risk factors on esophageal cancer (EC) may differ according to the portion of the esophagus where the tumor occurs. It is unclear why more esophageal squamous cell carcinomas (SCC) developed in the middle location. We carried out a multicenter case–control study in Taiwan to assess anatomical subsite risk discrepancy for this neoplasm in regard to the consumption of alcohol, tobacco and betel quid. Four hundred forty seven incident patients with pathology‐proven SCC of the esophagus (107 were upper‐third [U/3‐EC], 199 middle‐third [M/3‐EC] and 141 lower‐third [L/3‐EC] cases), as well as 1,022 gender, age and study hospital matched controls were analyzed by unordered polytomous logistic regression. All consumption of the three substances was related to the development of each subsite of EC, with a heterogeneously higher risk for current smokers (adjusted odds ratio (AOR) = 6.2) found in M/3‐EC and for current chewers, in U/3‐EC (AOR = 4.9). The joint risk of contracting lower two‐third EC for drinking and smoking appeared to significantly surpass those estimated by a multiplicative interaction model. Concomitant exposure to these two agents brought the risks of EC at all three subsites up to 10‐ to 23.9‐fold and additional tobacco‐free betel quid to a 30.3‐ to 75.0‐fold. In conclusion, tumor subsite discrepancy risk is related to prolonged exposure to tobacco and betel quid with inflorescence. Alcohol interacts with tobacco in a stronger supra‐multiplicative way in the middle portion of the esophagus, probably explaining why esophageal SCC occurs more commonly at this anatomical location.

Poverty Increases Type 2 Diabetes Incidence and Inequality of Care Despite Universal Health Coverage

OBJECTIVE The discrepancy of diabetes incidence and care between socioeconomic statuses has seldom been studied concurrently in nations with universal health coverage. We aimed to delineate whether income disparity is associated with diabetes incidence and inequality of care under a national health insurance (NHI) program in Asia. RESEARCH DESIGN AND METHODS From the Taiwan NHI database in 2000, a representative cohort aged ≥20 years and free of diabetes (n = 600,662) were followed up until 2005. We regarded individuals exempt from paying the NHI premium as being poor. Adjusted hazard ratios (HRs) were used to discover any excess risk of diabetes in the poor population. The indicators used to evaluate quality of diabetes care included the proportion of diabetic patients identified through hospitalization, visits to diabetes clinics, and completion of recommended diabetes tests. RESULTS The incidence of type 2 diabetes in the poor population was 20.4 per 1,000 person-years (HR, 1.5; 95% CI, 1.3–1.7). Compared with their middle-income counterparts, the adjusted odds ratio (OR) for the poor population incidentally identified as having diabetes through hospitalization was 2.2 (P < 0.001). Poor persons with diabetes were less likely to visit any diabetes clinic (OR, 0.4; P < 0.001). The ORs for the poor population with diabetes to receive tests for glycated hemoglobin, low-density lipoprotein cholesterol, triglycerides, and retinopathy were 0.6 (0.4–0.9), 0.4 (0.2–0.7), 0.5 (0.4–0.8), and 0.4 (0.2–0.9), respectively. CONCLUSIONS Poverty is associated not only with higher diabetes incidence but also with inequality of diabetes care in a northeast Asian population, despite universal health coverage.

The neoplastic impact of tobacco-free betel-quid on the histological type and the anatomical site of aerodigestive tract cancers

Little is known about any consequences of swallowing tobacco‐free betel‐quid (TF‐BQ) juice/remnants following chewing and its carcinogenic impact on the upper aerodigestive tract (UADT) to gastrointestinal tract (GIT). We investigated the neoplastic impact of TF‐BQ on different anatomical locations along UADT and GIT, and differences according to their histological categories. We conducted a multicenter case–control study examining patients with 2,163 pathology‐proven UADT and GIT cancers, comparing them with 2,250 control subjects. Generalized additive models, piecewise regression and polytomous logistic models were applied to identify possible dose‐dependent structures and cancer risks. Contrary to nonsignificant GIT‐adenocarcinoma risk (aOR = 0.9), TF‐BQ users experienced a 1.7‐ to 16.2‐fold higher risk of UADT‐squamous cell carcinomas than nonusers, with the peak risk discovered in oral neoplasms. We separately observed a curvilinear and linear TF‐BQ dose‐risk relationship in oral/pharyngeal/esophageal and laryngeal cancers. Chewers of betel inflorescence were generally at a greater UADT cancer risk. A higher first‐piecewise increased risk of esophageal cancer was recognized among areca‐fluid swallowers than among nonswallowers (continuous aOR = 1.12 vs. 1.03). TF‐BQ use accounted for 66.1–78.7% and 17.8–33.2% of the cases of oral/pharyngeal and esophageal/laryngeal cancers, respectively. However, a reduction from heavy TF‐BQ consumption to low‐to‐moderate consumption only reduced 11.3–34.6% of etiologic fraction of oral/pharyngeal cancers. Alcohol supra‐additively modified the risk of TF‐BQ in determining the development of oral, pharyngeal and esophageal cancers. In conclusion, the interplay of TF‐BQ and alcohol/tobacco use, combined with how chewing habit is practiced, influences carcinogenic consequences on anatomically diverse sites of UADT and GIT cancers, and histologically different types.

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.

The use of tobacco-free betel-quid in conjunction with alcohol/tobacco impacts early-onset age and carcinoma distribution for upper aerodigestive tract cancer

BACKGROUND  Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies. METHODS  To investigate the independent and synergistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study. RESULTS  A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral/pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6-2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5-71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibited earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. CONCLUSIONS  Tobacco-free betel-quid, in conjunction with alcohol and/or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms.

Second-hand smoke exposure and the factors associated with avoidance behavior among the mothers of pre-school children: a school-based cross-sectional study

BackgroundSecond-hand Smoke (SHS) exposure is a significant public health problem that may be responsible for serious health hazards for child. This study aimed to examine the exposure status of SHS and the factors associated with SHS avoidance behavior among the mothers of pre-school children.MethodsA cross-sectional study was used to obtain a sample of the mothers of pre-school children (n = 1,020) in 30 registered kindergartens in eastern Taiwan. Overall, 919 (a response rate of 90%) completed the questionnaires. Regression models were used to identify factors with respect to the avoidance behavior of SHS.ResultsThe prevalence of exposure to SHS was 70% and 50% for the mothers and their children, respectively. After adjusting for other variables, mothers who were current smokers (β = -0.260, p < 0.001), had spouses who smoked (β = -0.060, p < 0.05), SHS exposure (β = -0.138, p < 0.001), and/or children with exposure to SHS (β = -0.084, p < 0.05) were found to be less likely to avoid SHS, whereas mothers with a high knowledge score about SHS (β = 0.082, p < 0.01), positive attitudes (β = 0.274, p < 0.001) and a high self-efficacy level in regard to the avoidance of SHS (β = 0.397, p < 0.001) were observed to be more likely to avoid SHS. Regression analyses confirmed that the significantly factors associated with the avoidance behavior of SHS were self-efficacy, being a current smoker, and the attitude toward the avoidance of SHS to be that of 55.5% of the total variance explained (p < 0.001).ConclusionsThe high prevalence rate of exposure to SHS for mothers and their children suggests that a well-designed future intervention program should be implemented in regard to pre-school childrens mothers in order to prevent these mothers and their children from SHS exposure hazards, more particularly, to strengthen the knowledge base, to enhance self-efficacy and to foster a more positive attitude toward the avoidance of SHS in the mothers.