Yih-Gang Goan

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.

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.

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.

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.

Polymorphism in COX-2 modifies the inverse association between Helicobacter pylori seropositivity and esophageal squamous cell carcinoma risk in Taiwan: a case control study

BackgroundOverexpression of Cyclooxygenase-2 (COX-2) was observed in many types of cancers, including esophageal squamous cell carcinoma (ESCC). One functional SNP, COX-2 -1195G/A, has been reported to mediate susceptibility of ESCC in Chinese populations. In our previous study, the presence of Helicobacter pylori (H. pylori) was found to play a protective role in development of ESCC. The interaction of COX-2 and H. pylori in gastric cancer was well investigated. However, literature on their interaction in ESCC risk is scarce. The purpose of this study was to evaluate the association and interaction between COX-2 single nucleotide polymorphism (SNP), H. pylori infection and the risk of developing ESCC.MethodsOne hundred and eighty patients with ESCC and 194 controls were enrolled in this study. Personal data regarding related risk factors, including alcohol consumption, smoking habits and betel quid chewing, were collected via questionnaire. Genotypes of the COX-2 -1195 polymorphism were determined by PCR-based restriction fragment length polymorphism. H. pylori seropositivity was defined by immunochromatographic screening test. Data was analyzed by chi-squared tests and polytomous logistics regression.ResultsIn analysis adjusting for the covariates and confounders, H. pylori seropositivity was found to be inversely association with the ESCC development (adjusted OR: 0.5, 95% CI: 0.3 – 0.9). COX-2 -1195 AA homozygous was associated with an increased risk of contracting ESCC in comparison with the non-AA group, especially among patients with H. pylori seronegative (adjusted OR ratio: 2.9, 95% CI: 1.2 – 7.3). The effect was strengthened among patients with lower third ESCC (adjusted OR ratio: 6.9, 95% CI 2.1 – 22.5). Besides, H. pylori seropositivity conveyed a notably inverse effect among patients with COX-2 AA polymorphism (AOR ratio: 0.3, 95% CI: 0.1 – 0.9), and the effect was observed to be enhanced for the lower third ESCC patients (AOR ratio: 0.09, 95% CI: 0.02 – 0.47, p for multiplicative interaction 0.008)ConclusionH. pylori seropositivity is inversely associated with the risk of ESCC in Taiwan, and COX-2 -1195 polymorphism plays a role in modifying the influence between H. pylori and ESCC, especially in lower third esophagus.

Large Pedunculated Lipoma of the Esophagus

Pedunculated lipoma of the esophagus is rare and easily misdiagnosed in clinical practice. The presenting symptoms of esophageal lipoma are dysphagia, regurgitated mass and persistent sensation of a lump in the throat. The most frequent location of the tumor pedicle is the upper esophageal sphincter. Although the lipoma is pathologically benign, if it is large enough, it may cause airway obstruction secondary to the mechanical pressure to the larynx when the tumor is regurgitated. We present the case of a 67-year-old man who had the symptoms of dysphagia, nausea and vomiting. Esophagography and chest computed tomography revealed that he might have an esophageal submucosal or intraluminal tumor mass. Panendoscopy showed a pedunculated tumor mass within the esophageal lumen with its peduncle arising from the cervical esophagus. The tumor mass measured 9.0 x 4.7 x 2.5 cm in size. Thoracic approach via the right chest wall was performed for confirmation. After removal of the intraluminal mass, the patients symptoms dramatically improved. Pathology showed a lipoma arising from the submucosa of the esophagus.

Surgical Treatment of Metastatic Pulmonary Tumors

Background: Metastasectomy has been proved to be an opportunity for long-term survival for patients with various neoplasms with pulmonary metastases. A retrospective study was performed to analyze the results and identify the prognostic factors of surgical treatment for pulmonary metastases. Methods: From 1991 to 2003, a total of 73 patients who underwent surgical treatment for pulmonary metastases at the Kaohsiung Veterans General Hospital were enrolled for analysis. Results: The overall 5-year survival rate was 25.1%. The operation-related mortality rate was 2.74%. Gender, origins of the primary cancers, number of pulmonary metastases, and surgical procedures had no significant effect for those patients who underwent pulmonary metastasectomies. However, patients who had a disease-free interval longer than 36 months had a better 5-year survival rate than those who had a shorter disease-free interval (29.6% vs. 10.5%). Conclusion: Pulmonary metastasectomy is a safe and potentially curative procedure. The disease-free interval is an important prognostic factor for patients with pulmonary metastases.

Ectopic Pleura-based Thymoma Mimicking Mesothelioma: Report of a Case

Ectopic thymoma is rare, especially when it arises in the pleural cavity. We report a 32-year-old female patient with diffuse pleural thickening. Computed tomography(CT)-guided needle biopsy was done before operation and mesothelioma was impressed. Left pleuropneumonectomy was performed. After operation pathologic diagnosis of ectopic pleural thymoma was made.