Alcohol and Alcoholism Advance Access originally published online on May 18, 2009
Alcohol and Alcoholism 2009 44(4):353-357; doi:10.1093/alcalc/agp025
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Manganese Superoxide Dismutase (MnSOD) Polymorphism, Alcohol, Cigarette Smoking and Risk of Oesophageal Cancer
1 Department of Medicine I, University Hospital of Schleswig Holstein, Campus Lübeck, Germany,
2 Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Zhejiang, Hangzhou, People's Republic of China
3 Institute of Medical Biometry and Statistics, University Lübeck, Germany
* Corresponding Author: Department of Medicine II, Department of Gastroenterology and Oncology, Sauerbruchstrasse 5-7, 38440 Wolfsburg, Germany. Tel: +49-5361-801600; Fax: +49-5361-801643; E-mail: homannnils{at}hotmail.com
Received 26 January 2009; first review notified 3 March 2009; in revised form 2 April 2009; accepted 17 April 2009; advance access publication 18 May 2009
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Aims: Alcohol, tobacco smoke and Barrett's oesophagus as a consequence of gastro-oesophageal reflux are the main risk factors in oesophageal carcinogenesis. All risk factors may induce oxidative stress. Manganese superoxide dismutase (MnSOD) is one important repair enzyme for reactive oxidative stress (ROS)-induced damage. MnSOD polymorphisms in the –9 position of the signal sequence of the protein may lead to critical enzyme deficiency. The aim of the present study was to investigate the role of polymorphisms of MnSOD in patients with oesophageal cancer [n = 170, 61 patients with adenocarcinoma (AC), 109 patients with squamous cell carcinoma (SCC)] compared to heavy drinkers (n = 160) and healthy blood donors (n = 400). Methods: Genotyping was performed by PCR-RFLP analysis using genomic DNA extracted from whole blood. Results: The Ala/Ala genotype was 27.7% in cancer patients (29.5% AC, 26.6% SCC), 23.1% in patients with heavy alcohol abuse and 12.5% in the group of healthy blood donors. These results were not statistically significant after multivariate analysis controlling for age, sex, alcohol, cigarettes and interactions (odds ratio 0.92, 95% confidence interval = 0.63–1.36, for cancer patients versus heavy drinkers; odds ratio 1.02, 95% confidence interval = 0.51–2.03, for cancer patients versus blood donors; analysis by logistic regression). Subjects with an Ala/Ala genotype (81.3 g/day) had a significantly higher alcohol intake than those with Val/Ala (63.9 g/day) or Val/Val (53.8 g/day) genotype (P < 0.00001 by the Kruskal–Wallis test). Conclusions: MnSOD polymorphisms play no role in the genetic predisposition to oesophageal cancer. However, our data suggest a complex gene-to-phenotype interaction between the MnSOD genotype and alcohol misuse.