Cytochrome P450 2A6(CYP2A6) is known as a major enzyme responsible for C-oxidation of nicotine and 7-hydroxylation of coumarin. The article reviews different alleles of CYP2A6 that have been discovered, their effect on CYP 2A6 activity and the relationship between genetic polymorphism of CYP2A6 and smoking behavior as well as susceptibility of lung and esophageal cancer in different individuals.
Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2A6 ; Esophageal Neoplasms ; enzymology ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Lung Neoplasms ; enzymology ; genetics ; Mixed Function Oxygenases ; genetics ; Polymorphism, Genetic ; Research ; Smoking ; genetics

OBJECTIVETo study the association of genetic polymorphism of glutathione S-transferase M1 (GSTM1) and its susceptibility to esophageal cancer.

METHODSOdds ratio was employed to evaluate the risk of esophageal cancer and GSTM1 status. To take into account the possibility of heterogeneity across the studies, a statistical test for heterogeneity across the studies was performed. Both fixed and random effect Meta-analysis models were used. Publication bias was evaluated by funnel plot.

RESULTSA total of 1190 cases and 1964 controls from 11 studies was included. The pooled OR (with 95% CI) was 1.197 (0.846 - 1.692). Of 11 studies, 5 studies were stratified by smoking. In smoking groups, the pooled OR was 1.523 (1.099 - 2.109) while in non-smoking groups, the pooled OR was 0.933 (0.469 - 1.692).

CONCLUSIONOur results through Meta-analysis did not support the association between GSTM1 null genotype and esophageal cancer, but the smokers carring the GSTM1 null genotype might be associated with the increased risk of esophageal cancer.

Case-Control Studies ; Esophageal Neoplasms ; enzymology ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Glutathione Transferase ; biosynthesis ; genetics ; Humans ; Male ; Odds Ratio ; Polymorphism, Genetic ; Risk Factors ; Smoking ; adverse effects

Animals ; Carcinoma, Squamous Cell ; genetics ; Colorectal Neoplasms ; genetics ; metabolism ; Enzyme Activation ; Esophageal Neoplasms ; genetics ; Genome-Wide Association Study ; Head and Neck Neoplasms ; genetics ; Humans ; Neoplasms ; chemically induced ; enzymology ; genetics ; Phosphoinositide Phospholipase C ; chemistry ; genetics ; metabolism ; physiology ; Signal Transduction ; Skin Neoplasms ; chemically induced ; enzymology ; Stomach Neoplasms ; genetics ; Urinary Bladder Neoplasms ; metabolism ; pathology ; ras Proteins ; metabolism

BACKGROUND/AIMS: To investigate the differential expression of RING finger (RNF) proteins in Barrett esophagus (BE) and esophageal adenocarcinoma (EAC). METHODS: The differential expression of RNFs in normal esophagus (NE), BE, and EAC was screened using microarray assay. Real-time quantitative polymerase chain reaction (PCR), tissue microarray assay, and Western blot analysis were independently performed to detect the mRNA and protein expression of screened RNFs. RESULTS: The expression of nine RNFs in the BE or EAC was 2-fold higher than those in NE. Among these proteins, the RNF32 and RNF121 expression in BE was 20.3-fold and 16.4-fold higher, respectively, than that in NE, and the expression of RNF24, RNF130, RNF141, RNF139, RNF11, RNF14, and RNF159 was upregulated more than 2-fold compared with NE. The expression of nine RNFs was not only upregulated in the EAC but was also positively related to the RNF expression in BE. The PCR results also indicated increased expression of these RNFs in BE and EAC compared to NE. Furthermore, the mRNA expression of all RNFs, except for RNF141 in EAC, was dramatically higher than those in the BE. Similar results were also obtained from the Western blot analysis. CONCLUSIONS: A total of nine RNFs play critical roles in the progression of BE to EAC.
Adenocarcinoma/*enzymology/genetics ; Adult ; Aged ; Barrett Esophagus/*enzymology/genetics ; Carrier Proteins/genetics ; Disease Progression ; Esophageal Neoplasms/*enzymology/genetics ; Female ; Gene Expression Profiling ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Male ; Middle Aged ; Proteins/genetics ; *RING Finger Domains ; Receptors, Cell Surface/genetics ; Ubiquitin-Protein Ligases/genetics/*metabolism

OBJECTIVETo study the relationship of human telomerase reverse transcriptase (hTRT) and malignant transformation of esophageal dysplasia.

METHODSTelomerase activity and hTRT expression in esophageal dysplasia (n = 47), squamous cell carcinoma (n = 29) and normal esophagus (n = 11) were detected by telomeric repeat amplification protocol (TRAP) and in situ hybridization, respectively.

RESULTSTelomerase activity was detected in none of the 11 cases of normal esophageal tissues (0%) but in 21 of 47 cases (44.7%) of dysplasia, and in 25 of 29 cases (86.2%) of esophageal squamous cell carcinoma. There were statistically significant differences among the telomerase activity in normal esophagus, esophageal dysplasia, and in squamous cell carcinoma (chi(2) = 5.89, P < 0.05; chi(2) = 11.35, P < 0.01). hTRT mRNA was expressed in none of the 11 cases of normal esophageal tissues (0%) but in 23 of 47 cases (48.9%) of dysplasia, and in 24 of 29 cases (82.8%) of esophageal squamous cell carcinoma. There were statistically significant differences among the expression of hTRT mRNA in normal esophagus, esophageal dysplasia, and in squamous cell carcinoma (chi(2) = 6.99, P < 0.01; chi(2) = 7.32, P < 0.01). Significant correlation was found between the telomerase activity and the expression of hTRT mRNA (chi(2) = 57.91, P < 0.001).

CONCLUSIONThe mRNA expression of hTRT which paralleled to telomerase activity implied that there was a crucial role to play in regulating the activation of telomerase, and was closely related to the malignant transformation of esophageal dysplasia. hTRT might serve as a new, valuable biomarker to detect esophageal squamous cell carcinoma.

Adult ; Aged ; Biomarkers, Tumor ; analysis ; DNA-Binding Proteins ; Esophageal Neoplasms ; enzymology ; pathology ; Esophagus ; pathology ; Female ; Humans ; Male ; Middle Aged ; Precancerous Conditions ; enzymology ; pathology ; RNA, Messenger ; analysis ; Telomerase ; genetics ; metabolism

OBJECTIVETo investigate the expression of manganese superoxide dismutase (MnSOD) and to determine the relationship between MnSOD expression and clinicopathological features, biological behaviors in esophageal carcinoma.

METHODSImmunohistochemistry (SP) and RT-PCR were respectively used to detect the expression of MnSOD in 45 specimens of esophageal carcinoma tissues and normal esophageal mucosa (5 cm distant from the margin of cancer).

RESULTSThe positive rate of MnSOD protein expression was 31.1% in esophageal carcinoma tissues, significantly lower than 86.7% in the normal tissues (P < 0.05). The expressions of MnSOD mRNA and protein were significantly correlated with the lesion length, depths of invasion and histological grade (P < 0.05), but not with lymph node metastasis, lesion site and gross type of the tumor (P > 0.05). The relative content of MnSOD mRNA was (0.310 ± 0.036) and (0.482 ± 0.053) in the cancer and normal tissues, respectively, with a significant difference between the two groups (P < 0.05). The relative content of MnSOD mRNA was significantly related to lesion length, depths of invasion and histological grade (P < 0.05), but not correlated with lymph node status, lesion site and gross type of the tumor (P > 0.05).

CONCLUSIONThe expression of MnSOD protein and mRNA is decreased in esophageal carcinoma, suggesting that MnSOD gene may be closely associated with the carcinogenesis and the degree of malignancy. Detection of MnSOD expression may be useful in diagnosis, treatment and prognosis of esophageal carcinoma.

Adult ; Aged ; Carcinoma, Squamous Cell ; enzymology ; pathology ; Esophageal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Superoxide Dismutase ; genetics ; metabolism

OBJECTIVESTo investigate telomerase activity in esophageal squamous cell carcinoma (SCC) and its preneoplasia lesions, and to study the relationships between telomerase activity and cancer differentiation, cancer invasiveness, and lymphatic metastasis.

METHODSTelomerase activity in esophageal SCC tissues, adjacent dysplasia tissues and normal epithelia from the surgical edge were assessed by microdissection-TRAP (telomeric repeat amplification protocol)-silver staining assay.

RESULTSTelomerase activity was detected in 37 (82.2%) of 45 esophageal tumors, 23 (79.3%) of 29 dysplasias, and 2 (5%) of 40 normal epithelia. There was a significant difference in activity between dysplasia and normal epithelium, as well as between tumor and normal epithelium. Twenty-six (92.9%) of 28 tumors with lymphatic metastasis had detectable telomerase activity compared to 11 (64.7%) of 17 non-lymphatic metastasis tumors. These relationships were statistically significant (P < 0.05), but the one between telomerase activity and tumor grade was not.

CONCLUSIONTelomerase activity was high both in esophageal SCC and their preneoplasia lesions. The telomerase activity in SCC tissue was related to lymphatic metastasis, but not to cancer differentiation.

Adult ; Aged ; Carcinoma, Squamous Cell ; enzymology ; pathology ; Cell Differentiation ; Dissection ; Esophageal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Precancerous Conditions ; Repetitive Sequences, Nucleic Acid ; Telomerase ; genetics ; metabolism ; Telomere

OBJECTIVETo investigate the relationship between polymorphisms of methylenetetra-hydrofolate reductase gene 1298A-->C (MTHFR 1298A-->C) and its susceptibility of esophageal cancer (EC).

METHODSWe conducted a case-control study with 141 cases of EC and 228 population-based controls in Huaian city of Jiangsu province, China. Epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were identified by polymerase chain reaction.

RESULTS(1) The frequency of MTHFR 1298AA, AC and CC genotype were 63.8%, 34.0% and 2.1% in EC and 71.9%, 28.1% and 0.0% in controls, respectively (chi(2)(MH) = 6.69, P = 0.035). The frequency of the MTHFR 1298C allele was 0.19 for EC and 0.14 for controls. (2) Individuals having MTHFR 1298C allele and smoking habit were at a significantly higher risk of developing EC (adjusted OR = 3.48, 95% CI: 1.57 - 7.71) compared with those who having AA genotype but no smoking habit. Individuals having MTHFR 1298C allele and habit of frequent alcohol drinking were at an increased risk of developing EC (adjusted OR = 2.91, 95% CI: 1.20 - 7.08) compared with those with AA genotype and low consumption of alcohol. Individuals having MTHFR 1298C allele but no habit of tea drinking had a 3.52-fold (95% CI: 1.64 - 7.54) increased risk of developing EC compared with tea drinkers with AA genotype. As compared with subjects having AA genotype, low consumption of alcohol, no smoking habit but having habit of drinking tea, the individuals having 1298C allele, habits of frequent alcohol drinking, smoking but no habit of tea drinking had a 12.64-folds (95% CI: 1.39 - 114.65) increased risk of developing EC.

CONCLUSIONResults in the present study suggested that there was a coordinated effect between MTHFR 1298 genotypes and habits of smoking, alcohol drinking and tea consumption in the development of EC.

Adult ; Aged ; Alcohol Drinking ; Case-Control Studies ; China ; Esophageal Neoplasms ; enzymology ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Smoking

OBJECTIVETo investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma (ESCC) in Kazakh patients.

METHODSThe expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The expression of p-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas.

RESULTSERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 µmol/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 ± 3.49 in the ESCC tissues and 3.67 ± 7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa (P < 0.05), whereas there was no significant difference of t-ERK2 mRNA level between them(P > 0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87 ± 0.14 and 0.79 ± 0.10 in the ESCC tissues, and 1.10 ± 0.13 and 1.32 ± 0.12 in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue (P < 0.01). However, there was no significant difference between their t-ERK1/2 protein levels (P > 0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P < 0.05).

CONCLUSIONSERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.

Butadienes ; pharmacology ; Carcinoma in Situ ; enzymology ; pathology ; Carcinoma, Squamous Cell ; enzymology ; pathology ; Cell Line, Tumor ; China ; ethnology ; Enzyme Inhibitors ; pharmacology ; Esophageal Neoplasms ; enzymology ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; Nitriles ; pharmacology ; Phosphorylation ; RNA, Messenger ; metabolism

OBJECTIVETo investigate the effects of mTOR siRNA on mTOR-p70S6K signaling pathway in esophageal squamous cell carcinoma (ESCC) cells in vitro,and growth and apoptosis in transplanted tumor in nude mice.

METHODSmTOR siRNA was transfected into ESCC cell line EC9706 cells. The expressions of factors of the mTOR/p70S6K signaling pathway were detected by RT-PCR and Western blot. DNA contents and cell apoptosis were determined by flow cytometry, and cell proliferation was measured by CCK-8 assay. The effects of mTOR siRNA on the transplanted tumor growth were assessed in nude mice.

RESULTSThe levels of mTOR and p-p70S6K were significantly decreased (P < 0.05) while the level of p70S6K was increased (P < 0.05) in the cells transfected with mTOR siRNA, compared with that in untransfected cells and cells transfected with control siRNA. After being interfered by mTOR siRNA, the number of apoptotic cells was increased, cell proliferation became slower and cell cycle was arrested in G(1) phase compared with that in control cells. Also, mTOR siRNA inhibited the growth of transplanted tumor in vivo.

CONCLUSIONSmTOR siRNA can effectively interfere in mTOR-p70S6K signaling pathway, induce cell apoptosis and inhibit cell proliferation and tumor growth, suggesting that mTOR-p70S6K signaling pathway plays an important role in the carcinogenesis and development of esophageal squamous cell carcinoma.

Animals ; Apoptosis ; Carcinoma, Squamous Cell ; enzymology ; pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms ; enzymology ; pathology ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; pharmacology ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases ; genetics ; metabolism ; Transfection ; Tumor Burden