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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.

TitleA common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.
Publication TypeJournal Article
Year of Publication2011
AuthorsHaiman, C. A., Chen G. K., Vachon C. M., Canzian F., Dunning A., Millikan R. C., et al.
Corporate AuthorsGene Environment Interaction and Breast Cancer in Germany(GENICA) Consortium
JournalNat Genet
Volume43
Issue12
Pagination1210-4
Date Published2011 Dec
ISSN1546-1718
KeywordsAfrican Americans, Aged, Breast Neoplasms, Case-Control Studies, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Membrane Proteins, Middle Aged, Neoplasm Proteins, Polymorphism, Single Nucleotide, Receptors, Estrogen, Telomerase
Abstract

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

DOI10.1038/ng.985
Alternate JournalNat. Genet.
PubMed ID22037553
PubMed Central IDPMC3279120
Grant List090532 / / Wellcome Trust / United Kingdom
10118 / / Cancer Research UK / United Kingdom
11022 / / Cancer Research UK / United Kingdom
CA122340 / CA / NCI NIH HHS / United States
CA128978 / CA / NCI NIH HHS / United States
CA148065 / CA / NCI NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
R01 CA092447 / CA / NCI NIH HHS / United States
R01 CA122340 / CA / NCI NIH HHS / United States
R01 CA122340-04 / CA / NCI NIH HHS / United States
R01 CA128978 / CA / NCI NIH HHS / United States
R01 CA128978-04 / CA / NCI NIH HHS / United States
R25 CA092049 / CA / NCI NIH HHS / United States
U19 CA148065 / CA / NCI NIH HHS / United States
U19 CA148065-02 / CA / NCI NIH HHS / United States

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