于明暉臺灣大學：流行病學研究所林琦鈞Lin, Ci-JyunCi-JyunLin2007-11-272018-06-292007-11-272018-06-292005http://ntur.lib.ntu.edu.tw//handle/246246/56231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 27376680 bytesapplication/pdfen-US肝癌4q染色體精細輿圖分析HCC4qfine mappingthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/56231/1/ntu-94-R92842008-1.pdf