title: Evaluation of potential regulatory function of breast cancer risk locus at 6q25.1.
abstract: In a genome-wide association study conducted among Chinese women, we identified the single nucleotide polymorphism (SNP) rs2046210 at 6q25.1 for breast cancer risk. To explore a potential regulatory role for this risk locus, we measured expression levels of nine genes at the locus in breast cancer tissue and adjacent normal tissue samples obtained from 67 patients recruited in the Shanghai Breast Cancer Study. We found that rs2046210 had a statistically significant association with the expression levels of the AKAP12 and ESR1 genes in adjacent normal breast tissues. Women who carry the AA/AG risk genotypes had higher expressions of these two genes compared to those who carry G/G genotypes (P = 0.02 and 0.04 for the AKAP12 and ESR1, respectively). However, no significant differences of SNP rs2046210 with gene expression levels were found in tumor tissues. In The Cancer Genome Atlas samples, the AA/AG risk genotypes of SNP rs2046210 were associated with a significantly higher expression level of the AKAP12 gene and a lower level of the ESR1 gene in tumor tissue. Functional analysis using ENCODE data revealed that SNP rs7763637, which is in strong linkage disequilibrium with SNP rs2046210, is likely a potential functional variant, regulating the AKAP12 gene. Taken together, these results from our study suggest that the association between the 6q25.1 locus and breast cancer risk may be mediated through SNPs that regulate expressions of the AKAP12 gene.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37203, USA.|Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China and.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Division of Epidemiology , Department of Medicine , Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center , Vanderbilt University School of Medicine, Nashville , TN, 37203 , USA.
authors.forename: Chuanzhong
authors.initials: C
authors.lastname: Ye
authors.affiliation: Division of Epidemiology , Department of Medicine , Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center , Vanderbilt University School of Medicine, Nashville , TN, 37203 , USA.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Guo
authors.affiliation: Division of Epidemiology , Department of Medicine , Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center , Vanderbilt University School of Medicine, Nashville , TN, 37203 , USA.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Wen
authors.affiliation: Division of Epidemiology , Department of Medicine , Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center , Vanderbilt University School of Medicine, Nashville , TN, 37203 , USA.
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Epidemiology , Shanghai Cancer Institute , Shanghai , China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: Division of Epidemiology , Department of Medicine , Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center , Vanderbilt University School of Medicine, Nashville , TN, 37203 , USA.
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Division of Epidemiology , Department of Medicine , Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center , Vanderbilt University School of Medicine, Nashville , TN, 37203 , USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Division of Epidemiology , Department of Medicine , Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center , Vanderbilt University School of Medicine, Nashville , TN, 37203 , USA.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D059467:Transcriptome
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D018797:Cell Cycle Proteins