Associations Between Gene Expression Variations and Ovarian Cancer Risk Alleles Identified from Genome Wide Association Studies

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Nov 8

PMID 23133607

Citations 5

Authors

Hua Zhao

Jie Shen

Dan Wang

Yuqing Guo

Steven Gregory

Leonardo Medico

Qiang Hu

Li Yan

Kunle Odunsi

Shashikant Lele

Song Liu

Affiliations

Soon will be listed here.

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, rs10088218, rs1516982, rs10098821 on 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, rs10088218, rs1516982, and rs10098821 on 8q24.21 had the greatest number of significant associations (25, 16, and 38, respectively). Two possible cis-associations were observed between rs10098821 and c-Myc, and rs2072590 and HS.565379 (Permutated P = 0.0198 and 0.0399, respectively). Pathway enrichment analysis showed that several key biological pathways, such as cell cycle (P = 2.59×10(-06)), etc, were significantly overrepresented. Further characterization of significant associations between mRNAs and risk alleles might facilitate understanding the functions of GWAS discovered risk alleles in the genetic etiology of ovarian cancer.

Citing Articles

The association between TIPARP gene polymorphisms rs2665390 and ovarian cancer susceptibility.

Vahidi M, Houshmand M, Banoei M, Heidari F Gynecol Oncol Rep. 2023; 47:101175.

PMID: 37091214 PMC: 10113771. DOI: 10.1016/j.gore.2023.101175.

Ovarian cancer variant rs2072590 is associated with HOXD1 and HOXD3 gene expression.

Guo L, Peng Y, Sun L, Han X, Xu J, Mao D Oncotarget. 2017; 8(61):103410-103414.

PMID: 29262571 PMC: 5732737. DOI: 10.18632/oncotarget.21902.

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.

Hampras S, Sucheston-Campbell L, Cannioto R, Chang-Claude J, Modugno F, Dork T Oncotarget. 2016; 7(43):69097-69110.

PMID: 27533245 PMC: 5340115. DOI: 10.18632/oncotarget.10215.

Gene expression profiling analysis of ovarian cancer.

Yin J, Liu X, Wang B, Wang D, Wei M, Fang H Oncol Lett. 2016; 12(1):405-412.

PMID: 27347159 PMC: 4906568. DOI: 10.3892/ol.2016.4663.

Replication study for the association of seven genome- GWAS-identified Loci with susceptibility to ovarian cancer in the Polish population.

Mostowska A, Sajdak S, Pawlik P, Markowska J, Pawalowska M, Lianeri M Pathol Oncol Res. 2014; 21(2):307-13.

PMID: 25173882 PMC: 4422849. DOI: 10.1007/s12253-014-9822-6.

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