| 摘要: | 研究動機：已發表的全基因組關聯研究(Genome-wide association studies)主要以歐洲族群與東亞族群揭示許多與癌症多效性(Pleiotropic)基因，台灣族群並未被研究。本研究旨在發現台灣族群的癌症多效性(Pleiotropic)基因及位點，為亞洲族群的癌症多效性研究提供貢獻。
方法：從GWAS catalog資料庫與連鎖不平衡(Linkage disequilibrium) r2篩選出5,083個癌症位點，樣本來源於台灣精準醫療計畫（Taiwan Precision Medicine Initiative, TPMI）的台中榮民總醫院參與者，共計58,018個樣本。並使用全表型體學關聯研究確認台灣族群的癌症多效性基因及位點。
結果：在台灣族群中找到202個癌症多效性位點，其中有35個單體型。並驗證TERT基因及位點(5:1282204_A,5:1286401_G, 5:1282299_A )和FOXP4(6:41553372_C)在台灣族群中也具有癌症多效性。5:1282204_A、5:1286401_G、5:1282299_A在同一單體型中與甲狀腺癌、肺癌相關，而5:1282204_A在歐洲族群、東亞族群與台灣族群的癌症關聯相同，6:41553372_C與乳癌、頭頸癌相關。
結論：透過本研究發現在台灣族群上TERT(5:1282204_A,5:1286401_G, 5:1282299_A )為甲狀腺癌與肺癌相關的重要區域，未來研究可以再更深入探討這些位點與癌症之間的影響機制及蛋白質功能，已揭示在癌症發展中的具體作用。
Motivation: Published genome-wide association studies (GWAS) have primarily focused on European and East Asian populations, revealing many pleiotropic genes associated with cancer. However, the Taiwanese population has not been extensively studied. This research aims to identify pleiotropic genes and SNP related to cancer within the Taiwanese population, contributing to the understanding of pleiotropic cancer genes in Asian populations.
Methods: A total of 5,083 cancer SNPs were selected from the GWAS catalog database using linkage disequilibrium (r2). The samples were obtained from participants of the Taiwan Precision Medicine Initiative (TPMI) at Taichung Veterans General Hospital, totaling 58,018 samples. Phenome-wide association studies (PheWAS) were used to identify pleiotropic cancer genes and loci in the Taiwanese population.
Results: In the Taiwanese population, 202 cancer pleiotropic loci were identified, including 35 haplotypes. This study validated that the TERT gene and loci (5:1282204_A, 5:1286401_G, 5:1282299_A) and FOXP4 (6:41553372_C) also exhibit cancer pleiotropy in this population. The haplotype containing 5:1282204_A, 5:1286401_G, and 5:1282299_A is associated with thyroid cancer and lung cancer, and the association of 5:1282204_A with cancer is consistent across European, East Asian, and Taiwanese populations. The FOXP4 locus 6:41553372_C is associated with breast cancer and head and neck cancer.
Conclusions: This study identified the TERT region (5:1282204_A, 5:1286401_G, 5:1282299_A) as significantly associated with thyroid cancer and lung cancer in the Taiwanese population. Future research should further investigate the mechanisms and protein functions of these SNPs in cancer, to elucidate their specific roles in cancer development and progression. |
