人類基因多形性與胃癌危險性之關聯

胃癌迄今仍為人類主要之癌症，屬於一種多因子的疾病。胃癌的致病原因相當複雜，與許多基因甚至環境因子及幽門桿菌感染皆有關聯。也就是說，無法以少數幾個因子就來瞭解或評估胃癌，且其有關之致癌因子至今仍在發掘之中。為了尋找潛在的致病基因，可以利用基因組上一些小的變異來縮小基因圖的範圍，亦即可以利用個體基因之間的某個鹼基的變異來定位基因圖。單核酸多形性(Single Nucleotide Polymorphisms, SNPs)是人類基因多樣性最豐富的表現，而且是尋找常見複雜疾病基因遺傳最好的資源。經查文獻所得與胃癌有關之基因單核酸多形性之研究，包括p16, p21, p53, TNF, GST, IL-1, IL-4, MK...等等，但因大多數研究僅限於單一基因而已，不易同時比較各因子之間的關聯性。本研究即藉由同時研究比較數種與不同之人類胃癌致癌機轉相關之基因單核酸多形性，來探討複雜多因子之間的相關性。實驗結果顯示，p53，IL-1RN，TNF-alpha及GST-M1基因之單核酸多形性，與人類胃癌之危險性有關；而p16，p21，p53，IL-1Bp及MK基因之單核酸多形性，則與胃癌致癌機轉中之部分相關因子間之互動有關。至於IL-1Be5，IL-4p及IL-4i3基因之單核酸多形性，則因樣本數不足，尚未達到統計學上之顯著意義。人類基因單核酸多形性之研究，可以幫助釐清各個基因及其他因子與疾病的相關及和環境的複雜互動，並能藉以進一步瞭解疾病之致病機轉或用於評估疾病之預後。

關鍵字

胃癌；單核酸多形性

並列摘要

Gastric cancer plays an important role in human cancer death. This multi-factorial disease consisted of individual’s affected gene and also environmental factors. Up to now, there are growing numbers of new affected genes and associated factors being proposed. Single nucleotide polymorphisms (SNPs) are the most abundant form of human genetic variations and a resource for mapping complex genetic traits. The large volume of data produced by high-throughput sequencing projects is a rich and largely untapped source of SNPs. SNPs based on the difference among individuals, are usually either part of a gene or close to a gene that are more effective than conventional methods for locating disease genes. There was evidence that many oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, cell adhesion molecules, and the growth factor / reception system are involved in the cause of multi-step convention of normal epithelial cells to clinical gastric cancer. Up to now, the genes involved-in that have been proposed are p16, p21, p53, TNF, GST, IL-1, IL-4, MK.... SNPs can be found in some of the above genes. In this study, we use PCR-based restriction analysis to investigate the distribution of SNPs between the control group and gastric cancer patients. We enrolled the possible candidate genetic polymorphisms mentioned above, and in conjunction of environmental factors, to evaluated the association of genetic polymorphisms and human gastric cancer risk. There are significant associations of human gastric cancer risk with genetic polymorphisms in p53, IL-1RN, TNF-alpha and GST-M1 gene. After further stratification with different parameters, there are significant associations of genetic polymorphisms in p16, p21, p53, IL-1Bp and MK gene with some of the parameters. However, in genetic polymorphisms of IL-1Be5, IL-4p and IL-4i3, no significant association can be found owing to small sample size. In conclusion, PCR-based restriction analyses of SNPs are a powerful tool for the genetic study of human diseases. It can perform rapidly in amount of genomes that obtained from a group of patients. Data can be calculated for the susceptibility genes, resistant genes and interaction with environmental factors for many diseases. Disease can then be prevented if screening for the SNPs is done before it occurs, and many diseases can be diagnosed or predicted in some group of individuals.

並列關鍵字

gastric cancer ； single nucleotide polymorphism ； p16 ； p21 ； p53 ； TNF ； GST ； IL-1 ； IL-4 ； MK

參考文獻

43. Hirohashi S, Sugimura T. Genetic alterations in human gastric cancer. Cancer Cells 1991;3:49-52.

109. Sgambato A, Campisi B, Zupa A, Bochicchio A, Romano G, Tartarone A, Galasso R, Traficante A, Cittadini A. Glutathione S-transferase (GST) polymorphisms as risk factors for cancer in a highly homogeneous population from southern Italy. Anticancer Res 2002;22:3647-3652.

2. Ahmed K, Shitara Y, Kuwano H, Takenoshita S, Uchimuro K, Shinozawa T. Genetic variations of the midkine (MK) gene in human sporadic colorectal and gastric cancers. Intl J Mol Med 2000;6:281-287.

3. Ames BN. Cancer prevention and diet: help from single nucleoide polymorphisms. Proc Natl Acad Sci USA 1999;96:12216-12218.

4. Ara S, Lee PS, Hansen MF, Saya H. Codon 72 polymorphism of the Tp53 gene. Nucleic Acids Res 1990;18:4961.

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人類基因多形性與胃癌危險性之關聯

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