Microsatellite Instability And Val384Asp Mutations In Fetal Esophagus And Esophageal Cancer

TUInor is one of gene disease in torms of molecularbiologyHereditary and envirnmental factors act on the body and makemany genes changed, then result in malignancy These genesinclude oncogenes, arei-tumor genes and DNA Iinsmatch repairgenes(na). StUdies on envirnmental factors includechemical, biological and nutritional ones. It is reported thatchemical factors lilie nitrosamines can result in esOPhagealepithelium's malignancy and change its molecularbiology.Hereditary analysis showed that esoPhageal cancer in highincidence areas had evident herediop susceptibility. Geneticsanalysis on esoPhageal cancer patients fotmd that theirperipheral blood cells' ability to rePair damaged DNA reduced,DNA brittleness enhanced, and chromosomes changedobviously Studies on esoPhageal cancer have been cenered ononcogenes and ami-tumor genes, While on na are very few.5To study the na on esophageal cancer can help to probe themechanism of esophageal carcinogenesis. A fetUs rare1y contactsenvironmental factors, its characteristic of molecularbiology ismainly determined by its parents. To stUdy the fetlls'molecularbiology of high esophageal cancer incidence can helpto find many inbom factors or regionally factors oncarcinogCnesis, then to probe whether offsPring of conunonpeople has tuor susceptibility.The studies of human MMR are cotered on orCC, orLgnch Syndrome. The pathogeny of HNPCC is the mutations oftWo gelles, wrHl and hMSH2. In unCC patients MSI is ashigh as 90 per cen. MSI becomes an haportan parameter fOrprognosis and biology of the tumor and is an effective methodto screen the soCC.MSI marer D3Sl283 and WHl exon l2 are examinedin our study both in fetal esophagus and in esophageal cancer inorder to determine the effect of inbom factor in esoPhagealcarcinogenesis. then try to probe if there is any connectionbetWeen na and esophageal carcinogenesis.Mat6rials and Methods: (l) l2 fetal esophagis wereobtained from Anyang City and MengZhou County the highincidence areas for esophageal cancer. Feta age were 4 -- l0months(6.2512.45). Each specimen was got in an hour after6abortion. The uPper and midst of the fetal esoPhagUs was kop inliquid nitrOgen, then was stored in -80oC refogef8tory 3lesophageal cancer spechoens wer obtained from TUmorHospital of Anyang City The agC of patients were 35 -- 77years old(57.77 f l0.05). And each of them were got in an hourther operation, then was kePt in the liquid nitrogen and stOredin -80oC reffigeratOry (2) Gentalc DNA was extracted fromtWo kinds of spechoens by PrOteinase K digestion andphenol-chloroform eXtr8ction as described Previously D3Sl283.was exammed and PCR-SSCP was pdried tO detect themutation of All gene exonl2. Those specAnens' DNAwhich have abnormal strips was pefformed DNA analysis. (3)SPSSl0.0 software package was used to perform staistic'analysis.Results: (l) 4 fetal esophageal sPecimens were found MSIpositive, the rate is 33.3%. And l4 esoPhageal cancers werefound MSl positive, the rate is 45.2%. The difference of MSIbetWeen fetal esOPhagUs and esOPhageal cancer is of nonotability(P>0.05). Another 5(l6.l%) esophageal cancerspecimens manifest LOH. (2) There were 4 fetal esOPhagUsspecimens' PCR-SSCP manifeSted aberrat strips, and the fate is50%. l2 esophageal cancer specAnens medfested abefTat strips,the rate is 38.7%. The difference of PCR-SSCP between fetal7esophagus and esophageal cancer is of no notability(P>0.05). (3) DNA analysis showed that the mutation site lies in hMLHl exon!2 1151 base with T to A substitution which resulted in Val384Asp change.Conclusions: (1) There were high incidence of D3S1283 instability in esophageal cancer and fetal esophagus from high incidence area. (2)There were high rates of hMLHl exon!2 mutation in esophageal cancer and fetal esophagus, suggest maybe have relation to esophageal carcinogenisis .(3) Fetus from high-incidence areas has simi...