Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, kConFab/AOCS Investigators

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance in expression of these genes in breast carcinomas.

Original languageEnglish (US)
Pages (from-to)80140-80163
Number of pages24
JournalOncotarget
Volume7
Issue number49
DOIs
StatePublished - 2016

Fingerprint

Breast Neoplasms
Gene Expression
Single Nucleotide Polymorphism
DNA Helicases
Ribosomal Proteins
Mitochondrial Proteins
Linkage Disequilibrium
Individuality
DNA Repair
Estrogen Receptors
Genes
DNA Damage
Adenosine Triphosphatases
Genome
DNA
Neoplasms
Proteins

Keywords

  • Association studies
  • Breast cancer
  • Cis-regulatory variants
  • Differential allelic expression
  • Genetic susceptibility

ASJC Scopus subject areas

  • Oncology

Cite this

NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, ... kConFab/AOCS Investigators (2016). Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21. Oncotarget, 7(49), 80140-80163. https://doi.org/10.18632/oncotarget.12818

Association of breast cancer risk with genetic variants showing differential allelic expression : Identification of a novel breast cancer susceptibility locus at 4q21. / NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; NBCS Collaborators; kConFab/AOCS Investigators.

In: Oncotarget, Vol. 7, No. 49, 2016, p. 80140-80163.

Research output: Contribution to journalArticle

NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators & kConFab/AOCS Investigators 2016, 'Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21', Oncotarget, vol. 7, no. 49, pp. 80140-80163. https://doi.org/10.18632/oncotarget.12818
NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators, NBCS Collaborators et al. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21. Oncotarget. 2016;7(49):80140-80163. https://doi.org/10.18632/oncotarget.12818
NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; NBCS Collaborators ; kConFab/AOCS Investigators. / Association of breast cancer risk with genetic variants showing differential allelic expression : Identification of a novel breast cancer susceptibility locus at 4q21. In: Oncotarget. 2016 ; Vol. 7, No. 49. pp. 80140-80163.
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AU - Darabi, Hatef

AU - Dennis, Joe

AU - Devilee, Peter

AU - Dörk, Thilo

AU - Dos-Santos-Silva, Isabel

AU - Eriksson, Mikael

AU - Fasching, Peter A.

AU - Figueroa, Jonine

AU - Flyger, Henrik

AU - García-Closas, Montserrat

AU - Giles, Graham G.

AU - Goldberg, Mark S.

AU - González-Neira, Anna

AU - Grenaker-Alnæs, Grethe

AU - Guénel, Pascal

AU - Haeberle, Lothar

AU - Haiman, Christopher A.

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AU - Hallberg, Emily

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KW - Cis-regulatory variants

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