CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism

Abstract

Oesophageal cancer is one of the most common and lethal malignancies in the world. Despite many efforts, treatment is still ineffective for most cases; thus, the development of preventive strategies is crucial for decreasing the burden presented by this disease. Environmental factors, particularly nitrosamines, are thought to be involved in the genesis of oesophageal tumours, and knowledge about the expression of enzymes capable of activating pre-carcinogens in human oesophagus is very important for the development of preventive measures. We analysed the expression of CYP1A1, CYP1A2, CYP2A6/2A7, CYP2E1 and CYP3A4 mRNA in oesophageal mucosa of 50 patients by semi-quantitative RT-PCR. In five patients, who suffered from squamous cell carcinoma, we measured Nnitrosodimethylamine and N-nitrosodiethylamine metabolism in normal and tumorous tissue. CYP2A6/2A7 mRNA was expressed in 61% and CYP2E1 mRNA in 96% of the patients, but in the latter a lower degree of inter-individual variation was observed. These enzymes were expressed either in the distal or middle portions of the oesophagus of 90% of the patients. CYP1A1, CYP1A2 and CYP3A4 mRNA expression was not detected in any portion of the oesophagus. Oesophageal microsomes activated N-nitrosodimethylamine with a low degree of inter-individual variation and microsomes prepared from the tumour of a patient who strongly expressed CYP2A6/2A7 mRNA activated N-nitrosodiethylamine. We conclude that the human oesophagus expresses CYP2A6/2A7 and CYP2E1 and can activate nitrosamines. Notably, the expression of these enzymes is preferentially localized to the most common sites where tumours arise.

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh’s esophageal squamous cell cancer in Xinjiang, China

“…Over-representation of the variant CYP2E1 Rsa1 alleles was reported in ESCC [29] and a lower frequency of the Rsa1 variant allele was also found in ESCC patients than in controls [30] . In agreement with the result, studies in Japan and Brazil also found a significant increase in ESCC risks associated with the wild type Rsa1 [31,32] . Similarly, two studies in Chinese found an association between the CYP2E1 Rsa1 variant allele and decreased risk of ESCC [30,33] .…”

Helicobacter pylori infection, but not genetic polymorphism of CYP2E1, is highly prevalent in gastric cancer patients younger than 40 years

“…Other recent reports have suggested that CYP2E1 genetic polymorphism is responsible for susceptibility to GI cancers as well as lung cancer [21][22][23]. The present study yielded negative results regarding an association of CYP2E1 genetic polymorphism with the occurrence of gastric cancer in patients younger than 40 years.…”

“…Genetic polymorphisms of CYP2E1 have been shown to confer individual susceptibility to human cancers. Esophago-gastrointestinal cancers have been reported to be relevant to the expression of CYP2E1 and to N-nitrosamine metabolism [21][22][23]. It would thus be worthwhile to investigate whether the frequency of CYP2E1 restriction fragment-length polymorphism (RFLP) differs among gastric cancer patients younger than 40 years, patients in their sixties, and those 80 years or older.…”

Metabolism and Disposition Kinetics of Nicotine

“…CYP2A13 mRNA levels in nasal mucosa and lung are 5 and 9 times higher than CYP2A6 mRNA levels, respectively . CYP2A6 mRNA has been detected in nasal mucosa, lung, skin, coronary arteries, esophagus, and breast (Hellmold et al, 1998;Su et al, 2000;Janmohamed et al, 2001;Godoy et al, 2002;Borlak et al, 2003).…”