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研究生:林琦鈞
研究生(外文):Ci-Jyun Lin
論文名稱:肝細胞癌4q染色體精細輿圖分析:初步分析
論文名稱(外文):Fine Mapping of Hepatocellular Carcinoma Susceptibility Gene on 4q: Preliminary Analysis
指導教授:于明暉于明暉引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:流行病學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:27
中文關鍵詞:肝癌4q染色體精細輿圖分析
外文關鍵詞:HCC4qfine mapping
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背景與目的:肝細胞癌(hepatocellular carcinoma, HCC)為一種受到許多環境與遺傳因子影響之複雜性疾病。過去已有許多的loss-of-heterozygosity的研究指出在4q染色體上存在與HBV相關之HCC抑癌基因。本研究室先前的連鎖分析已在4q25位置發現初步顯著連鎖訊息。
材料與方法:我們以連鎖高峰為中心橫跨10 cM區域進行相關性研究,選擇14個單核苷多型性(single nucleotide polymorphism, SNPs)標記,分別對989名HBsAg陽性男性病例及956名HBsAg陽性之男性對照個案進行分析。
結果:以發病年齡進行分層分析,我們發現在發病年齡介於41~50歲之早發型的HCC中,SNP2在發病年齡介於41~50歲中,即使在校正多重檢定後仍具有顯著意義(P =.0003)。以相鄰標記進行半套體分析中,發現SNP1-SNP2在發病年齡介於41~50歲 (P value=.0006)及SNP8-SNP9在發病年齡>60歲 (P value=.0009)之半套体經過校正多重檢定後仍具有顯著意義。
結論:本研究發現SNP1-SNP2及SNP9-SNP9半套體和HCC顯著相關,但由於本研究的基因標記之分佈密度不夠密集,且涵蓋的區域不夠廣闊,未來有必要選取分佈更密且涵蓋更廣的SNP標記進行分析。
Background and Aim: Hepatocellular carcinoma (HCC) is a complex disease involving both environmental and genetic factors. Several loss-of-heterozygosity studies have suggested the existence of a tumor suppressor gene for HBV-related HCC on chromosome 4q. Our previous linkage study in HCC multiplex families has found a significant linkage signal on 4q25. The aim of this present study was to finely map the presumed HCC-susceptibility locus on 4q by using a large-scale case-control study.
Materials and Method: A total of 989 male HBsAg-positive HCC cases and 956 age-sex matched HBsAg-positive controls were included. We analyzed 14 single nucleotide polymorphisms (SNPs) distributed throughout the 2-HLOD-drop internal (~10 cM) around the linkage peak identified by our previous study.
Result: overall, none of the 14 SNPs were associated with HCC. However, SNP2 was significantly associated with early-onset HCC diagnosed between 41-50 years of age (P=.0003) this association remained statistically significant even after adjusting multiple comparisons by use of calculating false discovery rate. Haplotype analysis revealed that haplotype SNP1-SNP2 was associated with HCC diagnosed between 41-50 years of age (P=.0006), and SNP8-SNP9 was associated with HCC diagnosed at age >60 (P=0.0009).
Conclusions: We found haplotypes SNP1-SNP2 and SNP8-SNP9 were significantly associated with HCC. Further association study with a higher density of markers, which focused on a broader chromosomal region, is warranted.
前言 1
材料與方法 3
研究個案 3
問卷資料 4
實驗分析 4
分析方法 5
結果 6
環境因子在不同發病年齡知病例的分佈 6
單一基因標記分佈 6
連鎖不平衡分析 7
半套體分析 7
討論 8
參考文獻 11
表ㄧ 不同發病年齡之病例組環境因子分佈 21
表二 病例與對照組單一標記之基因頻率分佈 22
表三 不同發病年齡之半套體分析 23
圖一 24
圖二 25
圖三 26
附錄 27
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