associations between gene expression variations and ovarian cancer risk alleles identified from genome wide association studies协会之间的基因表达变化和卵巢癌风险等位基因从全基因组关联研究确定.pdfVIP

Associations between Gene Expression Variations and Ovarian Cancer Risk Alleles Identified from Genome Wide Association Studies 1 1 2 1 1 2 2 Hua Zhao *, Jie Shen , Dan Wang , Steven Gregory , Leonardo Medico , Qiang Hu , Li Yan , 3 3 2 Kunle Odunsi , Shashikant Lele , Song Liu * 1 Department of Cancer Prevention and Controls, Roswell Park Cancer Institute, Buffalo, New York, United States of America, 2 Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, New York, United States of America, 3 Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, United States of America Abstract Functional genetic variations play important roles in shaping phenotypic differences among individuals through affecting gene expression, and thus, very likely to influence disease susceptibility, such as cancer susceptibility. One critical question in this era of post-genome wide association studies (GWAS) is how to assess the functional significance of the genetic variations identified from GWAS. In the current study, with lymphoblastoid cell lines (LCLs) from 74 non-related women with familial ovarian cancer and 47 unrelated controls matched on gender and race, we explored the associations between seven ovarian cancer risk variants identified from GWAS (rs3814113 on 9p22.2, rs2072590 on 2q31, rs2665390 on 3q25, r rs1516982, ron 8q24.21, and rs2363956 on 19p13) and whole genome mRNA expression profiles. We observed 95 significant trans-associations at a permutation level of 0.001. Compared to the other risk variants, r rs1516982, and ron 8q24.21 had the greatest number of significant associations (25, 16, and 38, respe