利用HRM方法驗證6個已知SNPs與乳癌及病關係

全基因組相關性研究(Genome Wide Association Study;GWAS)，利用大量的實驗族群或人數，以及選取大量可能的基因之單核苷酸多型性（SNP），合併尋找可能致病的基因易感性。是一種對全基因組範圍內的常見遺傳變異基因總體關聯分析的方法。本實驗參考纖維芽細胞生長因子受體(Fibroblast growth factor receptor-2, FGFR2)基因與乳癌關係，選取纖維芽細胞生長因子受體(Fibroblast growth factor receptor-2, FGFR2) rs1219648 及rs2420946，並根據 GWAS 與乳癌的關係選取TNRC9 (Trinucleotide repeat containing 9) rs3803662、2q35 rs13387042、8q24 rs10505477、以及Reelin (RELN) rs17157903。以台灣人為研究對象，用高溶解曲線分析(High Resolution Melting Analyzsis ；HRM)的方法來檢測此6 個SNPs 與乳癌的關係，不同種族SNP 反應的allele 型會有不同相關性，FGFR2 rs1219648 及FGFR2 rs2420946 和乳癌的風險相關性在非洲裔美國婦女與白種人婦女有顯著性的風險但在台灣女性無顯著性差異；歐美GWAS 中觀察到與乳癌比較有顯著差異的SNPs 如RELN rs17157903、2q35 rs13387042、TNRC9 rs3803662 在本實驗的觀察結果與台灣女性無顯著性差異；此外， rs10505477 在乳癌患者和健康對照組 Genotype TT 與General genotype CC 相比有顯著性差異(OR＝0.65 ; 95% CI＝0.43，0.98; P＝0.041)，Alleles 亦有顯著性差異（OR＝0.76 ; 95% CI＝0.65，0.98; P＝0.031）,rs10505477 在乳癌患者中與雌激素受體（ER）和黃體素受體（PR）亦有相關聯。

關鍵字

基因多型性；乳癌

並列摘要

Genome Wide Association Study(GWAS) is an examination of all or most of the genes of different individuals of a particular species to see how much the genes vary from individual to individual. Different variations are then associated with different traits, such as diseases.We reffer GWAS results and choose 6 known SNPs related with breast cancer including Fibroblast growth factor receptor-2(FGFR2) rs1219648 and rs2420946、TNRC9 (Trinucleotide repeat containing 9) rs3803662、2q35 rs13387042、8q24 rs10505477、and Reelin (RELN) rs17157903 to examination by High Resolution Melting Analysis (HRM),and try to find out the association of Taiwan breast cancer with thease six known SNPs . SNP in different ethnicities has different associated .For example, FGFR2 rs1219648 and rs2420946 had significant risk with breast cancer for African -American women and Caucasian women；The other Genome Wide Association Studies(GWAS) discovered RELN rs17157903、2q35 rs13387042 and TNRC9 rs3803662 had significant association with breast cancer for European or American women .In our study ,none of thease five SNPs had significant association with breast cancer for Taiwan women. However, the 8q24 rs10505477genotype TT showed a significant association with breast cancer compared with general genotype CC (OR＝0.65 ; 95% CI＝0.43，0.98; P＝0.041), allele frequency among the 8q24 rs10505477 also showed a significant association with the breast cancer （OR＝0.76 ; 95% CI＝0.65，0.98; P＝0.031）.Moreover , 8q24rs10505477showed significant association with the clinical characteristics of Estrogen receptor（ER）and Progesterone receptor（PR）.