Study of p53 gene alteration as a biomarker to evaluate the malignant risk of Lugol-unstained lesion with non-dysplasia in the oesophagus

Mutations of the p53 gene are detected frequently in oesophageal dysplasia and cancer. It is unclear whether Lugol-unstained lesions (LULs) with non-dysplastic epithelium (NDE) are precursors of oesophageal squamous cell carcinoma (ESCC). To study the genetic alterations of NDE in the multistep process of oesophageal carcinogenesis, we determined the relationship between p53 mutations and LULs-NDE. Videoendoscopy with Lugol staining was performed prospectively in 542 oesophageal cancer-free subjects. Lugol-unstained lesions were detected in 103 subjects (19%). A total of 255 samples, including 152 LULs (NDE, 137; dysplasia, 15) and 103 paired samples of normal staining epithelium, were obtained from 103 subjects. After extraction of DNA and polymerase chain reaction analysis, direct sequencing method was applied to detect mutations of the p53 gene. The p53 mutation was detected in five of 137 samples with LULs-NDE (4%) and in five of 15 samples with dysplasia (33%). A hotspot mutation was found in 20% of LULs-NDE with p53 mutation and in 40% of dysplasia with p53 mutation. In contrast, no p53 mutations were found in 103 paired NDE samples with normal Lugol staining. In biopsy samples from oesophageal cancer-free individuals, the p53 missense mutations containing a hotspot mutation were found in NDE, which was identified as an LUL. These findings suggest that some LULs-NDE may represent the earliest state of oesophageal squamous cell carcinoma in Japanese individuals

Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China

In a cohort of 29 584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case–cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26–2.14, and 1.60; 1.15–2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88–1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies

Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey

BACKGROUND: The etiology of esophageal squamous cell cancer (ESCC) in high prevalence regions of China remains unclear. METHODS: Endoscopic biopsies were conducted among 7381 inhabitants aged from 25 to 65 of Anyang, China. RESULTS: In this study, 2.57, 0.20 and 0.16% of the participants had mild, moderate and severe squamous dysplasia, respectively; 0.19 and 0.08% showed squamous carcinoma in situ and invasive ESCC. Using deep well (depth >100 meters) as water source (odds ratio = 0.72, 95% confidence interval: 0.54-0.96) was negatively associated with ESCC and its precursors, whereas tobacco and alcohol use were not significantly associated with ESCC. CONCLUSIONS: Water source and other factors in this region need further evaluation by longitudinal studies. British Journal of Cancer (2010) 103, 1085-1088. doi:10.1038/sj.bjc.6605843 www.bjcancer.com Published online 10 August 2010 (C) 2010 Cancer Research UKOncologySCI(E)PubMed19ARTICLE71085-108810

Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk.</p> <p>Methods</p> <p>A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for <it>CYP2E1 </it>G1259C, <it>hOGG1 </it>C326G, <it>MTHFR </it>C677T, <it>MPO </it>G463A, and <it>ALDH2 </it>allele genes were identified in blood samples collected from all participants.</p> <p>Results</p> <p>The alleles <it>ALDH2 </it>and <it>MTHFR </it>C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the <it>ALDH </it>1*1 genotype, the <it>ALDH </it>2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of <it>MTHFR </it>C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of <it>ALDH </it>2 and TT/TC of <it>MTHFR </it>C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (OR_G) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus.</p> <p>Conclusions</p> <p>The study demonstrated that the genotypes <it>ALDH2*2 </it>and <it>MTHFR </it>677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.</p

Using NHANES oral health examination protocols as part of an esophageal cancer screening study conducted in a high-risk region of China

<p>Abstract</p> <p>Background</p> <p>The oral health status of rural residents in the People's Republic of China has not been extensively studied and the relationship between poor oral health and esophageal cancer (EC) is unclear. We aim to report the oral health status of adults participating in an EC screening study conducted in a rural high-risk EC area of China and to explore the relationship between oral health and esophageal dysplasia.</p> <p>Methods</p> <p>National Health and Nutrition Examination Survey (NHANES) oral health examination procedures and the Modified Gingival Index (MGI) were used in a clinical study designed to examine risk factors for esophageal cancer and to test a new esophageal cytology sampling device. This study was conducted in three rural villages in China with high rates of EC in 2002 and was a collaborative effort involving investigators from the National Institutes of Health and the Cancer Institute of the Chinese Academy of Medical Sciences.</p> <p>Results</p> <p>Nearly 17% of the study participants aged 40–67 years old were edentulous. Overall, the mean number of adjusted missing teeth (including third molars and retained dental roots) was 13.8 and 35% had 7 contacts or less. Women were more likely to experience greater tooth loss than men. The average age at the time of first tooth loss for those with no posterior functional contacts was approximately 41 years for men and 36 years for women. The mean DMFT (decayed, missing, and filled teeth) score for the study population was 8.5. Older persons, females, and individuals having lower educational attainment had higher DMFT scores. The prevalence of periodontal disease (defined as at least one site with 3 mm of attachment loss and 4 mm of pocket depth) was 44.7%, and 36.7% of the study participants had at least one site with 6 mm or more of attachment loss. Results from a parsimonious multivariate model indicate that participants with poor oral health wemore likely to have esophageal dysplasia (OR = 1.59; 95% CI 1.06, 2.39).</p> <p>Conclusion</p> <p>This report describes the first use of NHANES oral health protocols employed in a clinical study conducted outside of the United States. The extent and severity of poor oral health in this Chinese study group may be an important health problem and contributing factor to the prevalence of EC.</p

Telomerase activity of the Lugol-stained and -unstained squamous epithelia in the process of oesophageal carcinogenesis

Up-regulation of telomerase has been reported in many cancers. Our aim was to characterize telomerase activity in various states of the oesophagus to facilitate better understanding of carcinogenesis of oesophageal squamous cell carcinoma. During endoscopic examinations, we obtained 45 Lugol-stained normal epithelia, 31 Lugol-unstained epithelia (14 oesophagitis, 7 mild dysplasia, 5 severe dysplasia and 5 intramucosal cancer) and 9 advanced cancer. Telomerase activity was semi-quantified by a telomeric repeat amplification protocol using enzyme-linked immunosorbent assay, and expression of human telomerase reverse transcriptase mRNA was examined by in situ hybridization. In the Lugol-stained normal epithelia, telomerase activity increased in proportion to the increase of severity of the accompanying lesions, with a rank order of advanced cancer, intramucosal cancer, mild dysplasia and oesophagitis. In the Lugol-unstained lesions and advanced cancer, telomerase activity was highest in advanced cancer. Up-regulation of telomerase in normal squamous epithelium may be a marker of progression of oesophageal squamous cell carcinoma. Copyright 2001 Cancer Research Campaign © 2001 Cancer Research Campaignhttp://www.bjcancer.co

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.The African Esophageal Cancer Consortium is supported jointly by the International Agency for Research on Cancer and the Division of Cancer Epidemiology and Genetics of the Intramural Research Program of the National Cancer Institute