| Genetic polymorphisms are defined as variations in DNA that are observed in 1% or more of the population. Genetic polymorphisms may alter protein structure and function through a single nucleotide base substitution in a gene's coding region, and may increase or decrease gene expression either by affecting mRNA stability when occurring in a gene's 3' untranslated region or by altering transcription factor binding when occurring in the 5' promoter region. Alternatively, a polymorphism may have no discernable effect on the protein product and may lie within DNA regions that are not involved in gene transcription or translation. The study of genetic polymorphisms promises to help define patho-physiologic mechanisms, to identify individuals at risk for disease and to suggest novel targets for drug treatment. It is showed that the polymorphism of IL -ipgene is relate to gastric cancer or prestate of gastric cancer. Other genes' polymorphism, such as tumor necrosis factor a( TNF - a) promoter, 5,10 - meth-ylenetetrahydrofolate reductase and so on were also reported to be associated with susceptibility of gastric cancer or prestate diseases of gastric cancer. The methodology to study polymorphisms is simple, requiring only access to a poly-merase chain reaction machine, funding for reagents, and DNA samples from cases and controls.To understand the genetic predisposition of gastric cancer, we selected pepsinogen C gene as a report gene. Pepsinogen C (PGC) , also known as progas-tricsin, is the precursor of pepsin c or gastricsin. PGC can be detected through-out the stomach and proximal duodenum from the period of late infant stages to the whole adult stages. Therefore it was also considered to be a mature marker of stomach cells. It was reported that PGC not only was a digest enzyme but also might be a growth factor during the healing of stomach lesion and the change of serum PGC was associated with many kinds of stomach diseases. It was reported that an elevated PGC level (greater than or equal to 30jxg/l) was associated with about a threefold higher odds ratio for gastric ulcer than for duodenal ulcer. Miki et al. found that the serum pepsinogen levels of 137 stomach cancer patients , especially the PGA/PGC ratio were significantly lower than those of normal controls and correlated well with the extend of chronic gastritis associated with the cancerous stomach. The high sensitivity and specificity of this non ?invasive serum test to detect chronic gastritis suggested the possibility of its application to the mass screening of stomach cancer.PGC consists of two electrophoretic isozymogens. But up to now, no genetic variation was reported at the protein level. The human PGC gene, occupying approximately 10. 7kb, is separated into nine exons by eight introns. The PGC gene was localized to human chromosome 6p21. 1 - pter by analysis of mouse x human somatic cell hybrids. The recent linkage analysis demonstrated that the PGC gene is 22cM proximal to HLA cluster which has been investigated to determine the association with gastric disease, between D6S5 and D6S4, at a distance of 4.5 and 13. IcM. Between exon 7 and exon 8 of PGC gene, an about lOObp insertion - deletion was observed with several restriction enzymes. The polymorphism of PGC gene can be examined by both Southern blot and PCR methods. Azuma and Ohtaki reported that the polymorphism of PGC gene was related to gastric body ulcer. In our laboratory's studies, Yuan showed that the genotype of PGC gene polymorphism distributed in the 19 members of gastric cancer kindred was different from others whose families without gastric cancer history.In this study, we firstly focused on the distribution of the PGC gene polymorphism in gastric cancer patient group and health control group. For if the polymorphism of PGC gene has some relationship with gastric cancer, the distri-bution of the alleles of PGC gene in gastric cancer patient group and health control group will be different.Then at the base of the first paper, we tried detecting the di... |
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