2 research outputs found
A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
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 x
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 x 10(-9)), particularly in younger women (<50 years of
age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus
associated with estrogen receptor negative breast cancer subtypes in
multiple populations
Genome-wide association studies identify four ER negative-specific breast cancer risk loci
<p>Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.</p>