OBJECTIVETo investigate the relationship between tobacco smoking, drinking and p53 alteration in esophageal carcinoma.

METHODSLiterature on the relationship between p53 alteration in esophageal carcinoma and tobacco smoking, drinking through Meta-analysis were reviewed.

RESULTSIn 14 selected papers related to tobacco smoking, pooled odds ratio (OR) of tobacco smoking with P53 overexpression and p53 alteration were 1.99 (95% CI: 1.30- 3.06) and 1.64 (95% CI: 1.13 - 2.37), respectively (P < 0.05). Pooled OR of tobacco smoking with p53 mutation was 1.11 (95% CI: 0.47 - 2.76) (P > 0.05). In 11 selected papers on alcohol drinking, pooled OR of drinking with P53 overexpression, p53 mutation and p53 alteration were 1.30 (95% CI: 0.83 - 2.04), 1.13 (95% CI: 0.67 - 1.90) and 1.22 (95% CI: 0.87 - 1.72) respectively (P > 0.05).

CONCLUSIONThere were significant relations between tobacco smoking and p53 alteration while there were no significant relations between alcohol drinking and p53 alteration.

Alcohol Drinking ; Esophageal Neoplasms ; etiology ; genetics ; Female ; Genes, p53 ; genetics ; Humans ; Male ; Mutation ; Risk Factors ; Smoking ; adverse effects ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics

OBJECTIVETo study the etiological clues involved (in esophageal cancer in Linzhou, Henan, a high-incidence area for esophageal cancer) by analyzing p53 mutational spectrum from esophageal precancerous and cancerous lesions.

METHODSUsing bolt bioinformatic and Monte Carlo methods to analyze p53 mutation spectra from "The IARC Database of Somatic p53 Mutations in Human Tumors and Cell Lines", "p53 Database at Institute Curic" and to establish a local database based on these data using the FileMark Pro 3.0 software to allow fast and off-line analysis on a PC from the authors' laboratory.

RESULTSWe found that esophageal squamous cell carcinomas from Linzhou had a lower prevalence of base substitutions associated with strand bias than those from other areas (32.8% vs 39.8%). However, a higher prevalence of G:C-->A:T transitions at CpG site (29.6% vs16.4%) was found. Esophageal squamous cell carcinomas from Linzhou displayed a distinctive profile of mutation hotspots, including codons 273 (covers 11.3% of all missense mutations), 175 (9.7%), 158 (9.7%), 159 (6.5%) and 282 (6.5%), all of which were at the CpG site. Statistical analysis showed that the p53 mutation profiles between esophageal squamous cell carcinomas from Linzhou and those from other areas were different (P = 0.02). The p53 mutation profiles of esophageal squamous cell carcinomas from Linzhou and from other areas were also different from cancer of the head and neck.

CONCLUSIONData showed that the p53 mutational spectrum of esophageal squamous cell carcinomas from Linzhou baring the characteristics of those caused both by endogenous and exogenous mutagenic agents, suggesting the potential involvement of chronic inflammation, unique dietary habits and carcinogen exposure in the pathogenesis of esophageal squamous cell carcinoma in Linzhou.

Carcinogens, Environmental ; toxicity ; Carcinoma, Squamous Cell ; epidemiology ; etiology ; genetics ; China ; epidemiology ; DNA Mutational Analysis ; Esophageal Neoplasms ; epidemiology ; etiology ; genetics ; Feeding Behavior ; Female ; Genes, p53 ; genetics ; Humans ; Male ; Point Mutation ; Precancerous Conditions ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

BACKGROUNDCytochrome P450 2E1 (CYP2E1) has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined whether CYP2E1 RsaI and DraI polymorphism are associated with susceptibility to esophageal squamous cell carcinoma and the correlation between the genotypes and expression levels of CYP2E1 mRNA.

METHODSSeventy-seven patients with newly diagnosed, untreated esophageal squamous cell carcinoma and 79 healthy controls matched in age, gender and residence were recruited for the control study. An RsaI polymorphism in the 5'-flanking region and a DraI polymorphism in the sixth intron of the CYP2E1 gene, which could possibly affect its transcription, were determined in this study by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mRNA level of CYP2E1 was measured by quantitative real-time reverse transcription PCR.

RESULTSNo significant association of RsaI or DraI polymorphism of CYP2E1 with susceptibility of esophageal squamous cell carcinoma were demonstrated (OR = 1.67, 95% CI: 0.89 - 3.15, P = 0.11; OR = 1.11, 95% CI: 0.59 - 2.09, P = 0.74, respectively). With SHEsis software, no linkage disequilibrium was detected between RsaI and DraI polymorphism (D' = 0.528, r(2) = 0.27). When combined RsaI polymorphism with DraI polymorphism, the association between that carrying c2 allele and DD genotype and the risk for esophageal squamous cell carcinoma were found (OR = 5.77, 95% CI: 1.65 - 20.22). Compared with the normal controls, the mRNA levels with RsaI polymorphism, DraI polymorphism, or any combined genotypes in cases showed no statistical difference.

CONCLUSIONSThis study suggests that carrying c2 allele and DD genotype conferreded an elevated risk for esophageal squamous cell carcinoma. There was no significant statistical relationship between the genotypes c1/c2, D/C, or the combined allele and mRNA expression.

Aged ; Carcinoma, Squamous Cell ; etiology ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Esophageal Neoplasms ; etiology ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; RNA, Messenger ; analysis ; Risk

BACKGROUND/AIMS: Barrett's esophagus is a premalignant lesion of the esophagus in which normal squamous epithelium is replaced by intestinalized columnar epithelium. In Korea, adenocarcinoma associated with Barrett's esophagus is rare compared with that of Western country. The purpose of this study was to investigate the immunohistochemical expression of p53 and Ki-67 in Barrett's esophagus which had predictive value for cancer risk in Korea. METHODS: Ninety five patients (43 male and 52 female, median age 44, range 21-75) who have been suspected to have Barrett's esophagus by endoscopic assessment were enrolled in this study. Alcian blue (pH 2.5) and high ion diamine stain for the evaluation of specialized intestinal metaplasia (SIM) and immunohistochemical stain for p53 and Ki-67 were done. RESULTS: 57.9% (55/95) of biopsies from the columnar lined esophagus showed SIM, but no dyspalsia. 56.4% (31/55) of Barrett's esophagus showed sulfomucin positive colonic metaplasia. The p53 expression was observed in 10.9% (6/55) of the patients of Barrett's esophagus and all of them showed colonic metaplasia. Ki-67 labeling index showed no difference significantly. CONCLUSIONS: In Korea, 10.9% of Barrett's esophagus had p53 mutation and moreover all of them had colonic metaplasia. Consequently, we expect that these patients have high risk of developing dysplasia and adenocarcinoma and need careful follow-up.
Adenocarcinoma/etiology/genetics ; Adult ; Aged ; Barrett Esophagus/complications/*metabolism ; Esophageal Neoplasms/etiology/genetics ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/*metabolism ; Male ; Middle Aged ; Risk Factors ; Tumor Suppressor Protein p53/*metabolism

OBJECTIVETo investigate the relationship between the loss of heterozygosity(LOH) at 14 microsatellites in esophageal cancer and human papillomavirus (HPV) infection.

METHODSHPV-16,18 DNA was examined in 112 tumor specimens using fluorescence quantitative PCR. 112 tumor specimens and their matched blood DNAs were analyzed for LOH at 14 microsatellites by PCR and fluorescence-based DNA sequencing technology. The frequencies of LOH at 14 microsatellites were compared between HPV positive and negative specimens.

RESULTSHigh frequency of LOH was observed among chromosome arms 3p, 9p, 13q, 17p and 17q. The frequency of LOH was significantly higher at loci D13S260 and D6S497 in HPV positive specimens, comparing with HPV negative ones.

CONCLUSIONThe findings regarding loci with allele loss indicated that widespread chromosome instability might have existed in esophageal cancer. HPV positive specimens with higher frequency of LOH than negative ones at locus D13S260 and D6S497 suggesting that the target of HPV in esophageal cancer might serve as candidate genes at these two loci. In addition,this result also indicated that HPV might be a high-risk factor for esophageal cancer in Sichuan area with a high incidence of this cancer.

Adult ; Aged ; Chromosomal Instability ; genetics ; Esophageal Neoplasms ; etiology ; genetics ; virology ; Female ; Humans ; In Vitro Techniques ; Loss of Heterozygosity ; genetics ; Male ; Microsatellite Repeats ; genetics ; Middle Aged ; Papillomavirus Infections ; physiopathology ; Polymerase Chain Reaction

Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices.
Adenocarcinoma ; ethnology ; etiology ; genetics ; Alcohol Drinking ; adverse effects ; Asia ; epidemiology ; Asian Continental Ancestry Group ; genetics ; Carcinoma, Squamous Cell ; ethnology ; etiology ; genetics ; Esophageal Neoplasms ; ethnology ; etiology ; genetics ; European Continental Ancestry Group ; genetics ; Gastroesophageal Reflux ; complications ; Genetic Predisposition to Disease ; Humans ; Incidence ; Obesity ; complications ; Polymorphism, Single Nucleotide ; Risk Factors ; Smoking ; adverse effects ; United States ; epidemiology

OBJECTIVETo investigate the relationship between (GT)n polymorphism and esophageal cancer by analyzing the connection between microsatellite polymorphisms in the promoter of heme oxygenase-1 and the clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) in Han chinese population.

METHODSThe (GT)n repeats in HO-1 gene in 83 male and 43 female hospital-based patients with ESCC (aged between 40 and 79 years with a mean of (61 ± 8) years) and 134 healthy control individuals were obtained by DNA sequencing. Polymorphisms of the (GT)n repeats were generally grouped into three classes based on allele frequencies: class S alleles (<25 repeats), class M alleles (25 to 29 repeats), and class L alleles (≥30 repeats). The correlation between susceptibility and clinicopathological characteristics of ESCC were analyzed by χ2 test. For in vitro experiments, the transient-transfection assay was performed to explore the correlation between different lengths of (GT)n repeats and promoter activity by assessing the promoter activities of HO-1 gene in cultured Ecal09 cells treated with H2O2 by analysis of cariance.

RESULTSHigher frequencies of L-allele (25. 8% vs. 14. 9%, χ2 = 9. 520, P = 0. 002), L-allele carrier (41. 3% vs. 27. 6%, χ2 = 5. 381 , P = 0. 020) were found in patients with ESCC. Furthermore, the lymphatic metastasis rate (63. 5% vs. 41. 8%, χ = 5. 685, P = 0. 017) and the detection rate of poorly differentiated ESCC cell (53. 8% vs. 28. 4%, χ2 = 8. 335, P = 0. 004) was significantly higher in L-allele carriers compared to non-L-allele carriers. In transfection experiments, promoter activities of 5'-flanking regions of the HO-1 gene in Eca109 cells transfected with the recombinant gene carrying (GT)16 repeat after treatment with H2O2 increased (F = 23. 615,P = 0. 008). In H2O treated control group, compared to (GT)26 and (GT)36, the basal promoter activities of HO-1 gene carrying (GT)16 repeat increased (F =41. 376, P = 0. 003; F = 50. 761, P = 0. 002).

CONCLUSIONThe long (GT)n repeats of HO-1 gene promoter can increase the susceptibility of esophageal squamous cell carcinoma and the risk of lymphatic metastasis.

Alleles ; Asian Continental Ancestry Group ; Carcinoma, Squamous Cell ; etiology ; pathology ; Esophageal Neoplasms ; etiology ; pathology ; Female ; Gene Frequency ; Heme Oxygenase-1 ; genetics ; Humans ; Hydrogen Peroxide ; Lymphatic Metastasis ; Male ; Microsatellite Repeats ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Risk Factors ; Transfection

OBJECTIVETo investigate the prevalence of human papillomavirus (HPV), particularly of high-risk HPV in biopsy tissue specimens of esophageal carcinomas in Linzhou city.

METHODSGeneral nested primer sets were used to detected the whole HPV genotypes, following by HPV16 and 18 type specific PCR for the HPV16 and 18 detection respectively.

RESULTSAll 18 biopsy samples were HPV positive, and HPV 16 was detected in 13 of the 18 samples, HPV 18 was detected in 4 of the 18 samples.

CONCLUSIONThe high rate of HPV in the esophageal carcinoma samples suggested that HPV infection may be an important etiologic factor in the development of esophageal cancer in Linzhou city.

Adult ; Aged ; Biopsy ; China ; Esophageal Neoplasms ; etiology ; virology ; Esophagus ; pathology ; virology ; Female ; Genotype ; Human papillomavirus 16 ; isolation & purification ; Human papillomavirus 18 ; isolation & purification ; Humans ; Male ; Middle Aged ; Papillomaviridae ; genetics ; Polymerase Chain Reaction

OBJECTIVETo study the relationship between esophageal cancer (EC) and the ingestion of folate, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphisms in Kazakh area, Xinjiang.

METHODSA 1:2 matched case-control study was adopted. 120 cases diagnosed as esophageal cancer were collected with 240 population-based and hospital-based controls were selected by the same sex, same nationality and each pair's ages were permitted to differ within 5 years. MTHFR genotypes were detected by polymeerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the conditional logistic regression model was performed in this study.

RESULTSData showed that the ingestion of folate was related to EC in Kazakh (chi2 = 7.868, nu = 1, P < 0.01) with OR: 0.519 (95% CI:0.329-0.821) while more folate intake appeared to be the protective factor of EC in Kazakh. The MTHFR C677T genotype frequencies of EC group was different from the control group (chi2 = 15.823, nu = 1, P < 0.01). The individuals with 677CT, TT genotype had a 2.613-fold (95% CI: 1.628-4.194) increased risk of developing EC, compared to those who had 677CC genotype. Data from Interaction Analysis showed that more folate intake could reduce the incidence of esophageal cancer to the individuals who carried the MTHFR 677CT or TT genotypes.

RESULTSfrom multivariate conditional logistic regression analysis showed that: unsanitary drinking water, irregular eating, prefer eating peppery food, engorgement, crusted rice or wheat, having history of stomach or esophagus illness, carrying MTHFR 677CT or TT genotypes were risk factors of esophageal cancer while taking in more folate was the protective factor of EC.

CONCLUSIONLacking of folate intake were mainly risk factor and the polymorphisms of MTHFRC677T gene were susceptibility factor of esophageal cancer in Kazakh in Xinjiang.

Adult ; Aged ; Aged, 80 and over ; China ; Esophageal Neoplasms ; epidemiology ; etiology ; genetics ; Female ; Folic Acid ; administration & dosage ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Logistic Models ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; genetics