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

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.

Figure 1

A regional plot of the –log₁₀ P values for SNPs at the chromosome 5p15 risk locus from the meta-analysis of the AABC and TNBCC stage 1 studies. SNP rs10069690 is designated with the purple diamonds. The colors depict the strength of the correlation (r²) between SNP rs10069690 and the SNPs tested in the region. The correlation is estimated using 1000 Genomes Project (1KGP) data for the HapMap CEU population (June 2010). Squares are SNPs that were genotyped in AABC and TNBCC. Circles are SNPs that were genotyped in one study and imputed in the other or imputed in both studies. The blue line indicates the recombination rates in centimorgans (cM) per megabase (Mb). Also shown are the SNP Build 36 coordinates and genes in the region.