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

Journal article

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.

Authors: Haiman, C; Chen, G; Vachon, C; Canzian, F; Dunning, A

• Publication status: Published
• Journal: Nature genetics
• Volume: 43
• Issue: 12
• Pages: 1210-1214
• Publication date: 2011-12-01
• DOI: 10.1038/ng.985
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Female; Humans; European Continental Ancestry Group; Genetic Predisposition to Disease; Telomerase; Breast Neoplasms; Neoplasm Proteins; Genotype; Membrane Proteins; Genetic Loci; African Americans; Polymorphism, Single Nucleotide; Middle Aged; Case-Control Studies; Genome-Wide Association Study; Gene Environment Interaction and Breast Cancer in Germany (GENICA) Consortium; Aged; Receptors, Estrogen