Ein-Long Kao

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.

The importance of classification in sympathetic surgery and a proposed mechanism for compensatory hyperhidrosis: experience with 464 cases.

BackgroundCompensatory hyperhidrosis is the most troublesome side effect and the leading cause of regret with sympathetic surgery. A new classification is proposed to make the procedure more selective and to minimize the side effects and regret rate. Also, a proposed mechanism for compensatory hyperhidrosis is discussed.MethodsBetween January 2002 and July 2003, 464 patients with various sympathetic disorders underwent thoracoscopic sympathectomy/sympathicotomy (ETS) or sympathetic block by clipping (ESB) at various levels according to the authors’ classification. The surgery was performed on an outpatient basis. The rates of success, compensatory hyperhidrosis, and regret were recorded.ResultsAll the patients were followed up for 17 to 35 months. All excessive sweating was effectively stopped to varying degrees. The 25 patients with palmar hyperhidrosis who insisted on receiving ETS of T4 experienced no compensatory hyperhidrosis. Of the 54 patients with facial blushing who received ESB of T2, 23 experienced compensatory hyperhidrosis. Nine patients expressed regret and requested removal of the clips. Of the 33 patients with craniofacial hyperhidrosis who received ESB of T3, 9 experienced compensatory hyperhidrosis. Three expressed regret, and reverse procedures were performed. For 324 patients with palmar hyperhidrosis receiving ESB of T4, no compensatory hyperhidrosis was found. Only two expressed regret because of discomfort. No compensatory hyperhidrosis or regret was noted with 28 patients who received ESB of T5 for axillary sweating. There was no recurrence in the entire series.ConclusionsDifferent procedures are recommended for different sympathetic disorders according to the classification. The higher the level of sympathetic ganglion blockade, the higher is the regret rate. Therefore, for T2 and T3 ganglion, endoscopic thoracic sympathetic block by the clipping method is strongly recommended because of its reversibility.

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.

Risk of betel chewing for oesophageal cancer in Taiwan

Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other confounders, we found that subjects who chewed from 1 to 495 betel-year and more than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95% Cl = 1.3–10.1) and 9.2-fold risk (95% Cl = 1.8–46.7), respectively, of developing oesophageal cancer, compared to those who did not chew betel.

SULT1A1 polymorphism and esophageal cancer in males

Sulfotransferase (SULT) 1A1 detoxifies and bioactivates a broad spectrum of substrates including xenobiotics. It has been suggested that the SULT1A1 his (histidine) allele, which is caused by a his for arg (arginine) substitution due to a G→A transition at codon 213, carries a significantly higher risk for women to develop breast cancer. We investigated the association between the SULT1A1 arg/his genotype and esophageal cancer in men, 187 cases of esophageal squamous cell carcinoma and 308 controls from 3 medical centers in Taiwan. Cigarette smoking, areca chewing and alcohol consumption were the major risks for developing esophageal cancer. The frequencies of arg/his in cases and controls were 27.8% (52/187) and 11.0% (34/308), respectively (p < 0.0001). No subjects carried his/his. After adjusting for substance use and other covariates, individuals with arg/his had a 3.53‐fold higher risk (95% CI = 2.12–5.87) of developing esophageal cancer than those with arg/arg. Unexpectedly, this positive association was found to be even stronger (adjusted OR = 4.04–4.80) among non‐smokers, non‐drinkers or non‐chewers. Our findings suggest that the SULT1A1 his213 allele is important in the development of esophageal cancer in men.

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.

Genetic polymorphisms of cytochrome P4501A1 and oesophageal squamous-cell carcinoma in Taiwan

Several in vitro studies have demonstrated that genetic polymorphisms result in functionally significant changes in cytochrome p4501A1 (either CYP1A1 MspI or exon 7) but the few epidemiologic studies of these polymorphisms in oesophageal squamous-cell carcinoma have been inconclusive. These inconclusive results motivated us to further examine the relationship between CYP1A1 MspI and exon 7 polymorphisms and risk of oesophageal cancer. In total, 146 cases of oesophageal squamous-cell-carcinoma and 324 control cases (a total of 470 cases) were genotyped from records at three Taiwan hospitals. No significant association was noted for the CYP1A1 MspI polymorphism variable between carcinoma and control cases. In contrast, the frequency of Ile/Ile, Ile/Val, and Val/Val in exon 7 was 68 (46.6%), 62 (42.5%), and 16 (11.0%) in carcinoma cases and 179 (55.3%), 127 (39.2%), and 18 (5.6%) in control cases, respectively. After factoring out other potential contributing factors, patients with Val/Val showed a 2.48 (95% CT=1.15–5.34) greater risk of developing oesophageal cancer than those with Ile/Ile. A slightly (albeit not significantly) greater risk was identified in subjects with Ile/Val (OR=1.34; 95% CI=0.86–2.07). These findings suggest that an exon 7 polymorphism, not a MspI polymorphism, in CYP1A1 may be pivotal in the development of oesophageal cancer.

Association between p21 codon 31 polymorphism and esophageal cancer risk in a Taiwanese population

P21, which regulates the cell growth cycle, is crucial for normal growth and differentiation. One polymorphism in the p21 codon 31 produces variant proteins with an amino acid change (serine (ser) or arginine (arg)). Although several epidemiologic studies have examined the effect of this polymorphism on cancer risk, the findings remain inconclusive, which has motivated us to evaluate the relationship between p21 codon 31 polymorphism and esophageal cancer risk. In this study, 128 cases of esophageal squamous cell carcinoma and 178 control cases from two hospitals in southern Taiwan were genotyped. Frequencies of arg/arg, arg/ser and ser/ser were 23 (18.0%), 62 (48.4%) and 43 (33.6%) in carcinoma cases and 51 (28.6%), 84 (47.2%) and 43 (24.2%) in control cases, respectively. After factoring out other potential contributing factors, patients with ser/ser or arg/ser were 2.17 times more at risk (95% CI=1.03-4.56) for developing esophageal cancer than those with arg/arg. Males (n=274) were found to have a slightly stronger association (adjusted OR=2.45; 95% CI=1.03-5.80). Although the sample size is relatively small, these findings suggest that a codon 31 polymorphism in p21 may be associated with the development of esophageal cancer.

Helicobacter pylori Infection: A Protective Factor for Esophageal Squamous Cell Carcinoma in a Taiwanese Population

AIM:Many researchers have reported the inverse relationship between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma risk, but very few studies have examined the association between H. pylori infection and the development of esophageal squamous-cell carcinoma (ESCC). Therefore, the aim of this study is to evaluate the relationship between H. pylori infection and ESCC risk.METHOD:Subjects were cancer cases, pathologically proven to have ESCC, in two large medical centers in Kaohsiung metropolitan of southern Taiwan between August 2000 and May 2003. Controls were from the healthy subjects who lived in Kaohsiung metropolitan and voluntarily participated in one large multiyear of gene-environmental study. In total, 127 cases (116 males and 11 females) and 171 controls (161 males and 10 females) were recruited in the same period of time for interviews. H. pylori seropositivity was determined by an enzyme-linked immunosorbant assay measuring IgG.RESULTS:A total of 28 (22.1%) and 74 (43.3%) out of 127 cases and 171 controls, respectively, had positive H. pylori infection. After adjusting for other covariates, subjects with positive H. pylori infections had a significantly reduced risk (adjusted odds ratio (AOR) = 0.51; 95% CI = 0.27–0.96; P = 0.037) of developing ESCC than those without. This result was even more pronounced in the groups of younger subjects, nonsmokers, or nondrinkers. In addition, among the 117 cancer patients who provided information about site of cancer lesion, the present study found that subjects with cancer lesions in the lower third of the esophagus had significantly fewer positive H. pylori infections (AOR = 0.34; 95% CI = 0.14–0.80; P = 0.013) than controls.CONCLUSION:Our findings suggest that H. pylori infection may protect against the development of ESCC. Additional studies are needed to confirm these findings.

Relationship between site of oesophageal cancer and areca chewing and smoking in Taiwan.

Among 309 male patients, those who had heavily consumed betel and tobacco were more likely than nonchewers (OR=2.91; 95% CI=1.36–6.25) and nonsmokers (OR=2.49; 95% CI=1.02–6.08) to develop cancer in the upper and middle third of the oesophagus, respectively; the effects of alcohol did not dominate in any third.