Abstract
Background CHRNA5-A3-B4, the gene cluster encoding nicotinic acetylcholine receptor subunits, is associated with lung cancer risk and smoking behaviors in people of European descent. Because cigarette smoking is also a major risk factor for esophageal squamous cell carcinoma (ESCC), we investigated the associations between variants in CHRNA5-A3-B4 and ESCC risk, as well as smoking behaviors, in a Chinese population.MethodsA case-control study of 866 ESCC patients and 952 healthy controls was performed to study the association of polymorphisms (rs667282 and rs3743073) in CHRNA5-A3-B4 with cancer risk using logistic regression models. The relationships between CHRNA5-A3-B4 polymorphisms and smoking behaviors that can be quantified by cigarettes smoked per day (CPD) and pack-years of smoking were separately estimated with Kruskal-Wallis tests among all 840 smokers.Results CHRNA5-A3-B4 rs667282 TT/TG genotypes were associated with significantly increased risk of ESCC [adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.03 – 1.69, P = 0.029]. The increased ESCC risk was even higher among younger subjects (≤60 years) (OR = 1.44, 95% CI = 1.04 – 1.98, P = 0.024). These effects were not found in another polymorphism rs3743073. No evident association between the two polymorphisms and smoking behaviors was observed.ConclusionsThese results support the hypothesis that CHRNA5-A3-B4 is a susceptibility gene cluster for ESCC. The relationship between CHRNA5-A3-B4 and smoking behaviors in a Chinese population needs further investigation.
Highlights
Esophageal cancer is the eighth most common cancer in the world, and there were 482 300 newly diagnosed cases worldwide in 2008 [1,2]
The exact etiology of esophageal squamous cell carcinoma (ESCC) remains to be identified, cigarette smoking has been demonstrated as the major factor that contributes to the development of ESCC in accumulating epidemiological and clinical studies [1]
Nicotine in tobacco triggers the psychological and neurobiological effects that are associated with smoking consumption and addiction [5], while nitrosamines are important carcinogens in tobacco that contribute to the development of many smoking-related cancers, including lung cancer and ESCC [6]
Summary
Esophageal cancer is the eighth most common cancer in the world, and there were 482 300 newly diagnosed cases worldwide in 2008 [1,2]. The nicotinic acetylcholine receptor (nAChR) belongs to the superfamily of ligand-gated ion channels, and it is activated by acetylcholine (Ach), choline and nicotine It is involved in the regulation of nicotine and nitrosamines [4]. Nicotine in tobacco triggers the psychological and neurobiological effects that are associated with smoking consumption and addiction [5], while nitrosamines are important carcinogens in tobacco that contribute to the development of many smoking-related cancers, including lung cancer and ESCC [6]. Because cigarette smoking is a major risk factor for esophageal squamous cell carcinoma (ESCC), we investigated the associations between variants in CHRNA5-A3-B4 and ESCC risk, as well as smoking behaviors, in a Chinese population
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