| Linzhou (formerly Linxian) and nearby counties in Henan province, northern China have been well recognized as the highest incidence area for esophageal squamous cell carcinoma (SCC) in the world. SCC remains the leading cause of cancer-related deaths in these areas. A remarkable epidemiological characteristic for SCC is the occurring together with gastric cardia adenocarcinoma (GCA) in the same high-incidence area. It is noteworthy that the concurrent cancers from esophagus and gastric cardia in same patient (CC) is not uncommon in this area, with an incidence of 0.4-2.5%. GCA is still an understudied subject and largely unknown for the mechanism of carcinogenesis. Moreover, the prognosis for both SCC and GCA is very poor; the five years survival rate for these two cancers at the late and advanced stages is only 10%. Lacking of early diagnostic biomarker as well as the deficiency of effective and specific treatment and prevention leads to the poor prognosis and highermortality for SCC and GCA in these areas. Accumulated data have indicated that carcinogenesis both for SCC and GCA is a multistage progress. The early indicator for the subjects predisposed to SCC and GCA is the abnormal proliferation of epithelial cells, morphologically manifested as basal cell hyperplasia (BCH), dysplasia (DYS) and carcinoma in situ (CIS), which could be considered as precancerous lesions for SCC. Intestinal metaplasia and DYS have been recognized as precancerous lesions for gastric cardia carcinogenesis. Precancerous lesions have potential of reversibility, i.e., they may stay in the same satge for couple of years, or progress to more severe lesions, even return to normal. Apparently, it is limited to explain this phenomenon in morphological level. To further elucidate the possible mechanisms of SCC and GCA carcinogenesis, the present study was designed to establish data bank through endoscopic biopsy and balloon cytology screening, follow-up and intervention on subjects at high-incidence area in Henan and to determine the alterations of protein files (p53-Rb system, including p53, Rb, p16, p14, p15, wafl, Cyclin Dl, PCNA, etc) and genetic changes, polymorphisms of CYP1A1, CYP2E1, mEH, GSTM1, GSTT1 and GSTP1, comparative genomic hybridization (CGH).MATERIALS AND METHODSSubjects:All the subjects enrolled in this study were from Linzhou and nearby counties in Henan, the highest incidence area for both SCC and GCA (n=l 1,230). The symptom-free subjects were those from mass survey for early detection of SCC and GCA, there was no selection process involved. All the inhabitants in these areas withage of over 35 years were invited for screening and intervention trail. The detailed information for these subjects including age and sex was described in each sections followed. The patients with SCC and GCA in this study were also from the same areas. Surgically resected specimens were collected from those without chemotherapy or radiotherapy before operation. The detailed information for the patients was addressed in each section.Endoscopy and Biopsies ExaminationsTwo biopsy samples were taken at standard positions, one each from the middle third (30-32cm from incisor teeth) and the lower third (2-3cm above the junction of the esophagus and cardia) of the esophagus. Another one was taken at gastric cardia. Additional biopsies were taken when there were macroscopic lesions. The biopsy specimens were fixed in 85% alcohol, embedded in paraffin, and sectioned at 5 m. Balloon cytological examinationEach subject was asked to swallow the balloon, and the balloon attached to the tube was gently passed down the esophagus to the level of the gastric cardia (50 cm from the front teeth). The distended balloon was gently withdrawn, with some release of air if resistance was encountered. Three smears were made from each person by rolling the balloon on glass slides and immediately fixing in 95% alcohol. All smears were stained with the Papanicolaou method and examined under light microscope. Criteria for histology and cytology...
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