19p13.1 is a triple-negative-specific breast cancer susceptibility locus.
Title | 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Stevens, K. N., Fredericksen Z., Vachon C. M., Wang X., Margolin S., Lindblom A., et al. |
Corporate Authors | GENICA Network, kConFab Investigators, & AOCS Group |
Journal | Cancer Res |
Volume | 72 |
Issue | 7 |
Pagination | 1795-803 |
Date Published | 2012 Apr 1 |
ISSN | 1538-7445 |
Keywords | Breast Neoplasms, Chromosome Mapping, Chromosomes, Human, Pair 19, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Risk |
Abstract | The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 × 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 × 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 × 10(-13)]. Thus, 19p13.1 is the first triple-negative-specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. |
DOI | 10.1158/0008-5472.CAN-11-3364 |
Alternate Journal | Cancer Res. |
PubMed ID | 22331459 |
PubMed Central ID | PMC3319792 |
Grant List | 090532 / / Wellcome Trust / United Kingdom 10118 / / Cancer Research UK / United Kingdom 11022 / / Cancer Research UK / United Kingdom 5U01 CA113916 / CA / NCI NIH HHS / United States C1287/A10118 / / Cancer Research UK / United Kingdom C1287/A12014 / / Cancer Research UK / United Kingdom C490/A10124 / / Cancer Research UK / United Kingdom C8197/A10123 / / Cancer Research UK / United Kingdom C8197/A10865 / / Cancer Research UK / United Kingdom CA116201 / CA / NCI NIH HHS / United States CA122340 / CA / NCI NIH HHS / United States CA58860 / CA / NCI NIH HHS / United States CA92044 / CA / NCI NIH HHS / United States P30 CA016056-32 / CA / NCI NIH HHS / United States P50 CA116201 / CA / NCI NIH HHS / United States P50 CA116201-06A1 / CA / NCI NIH HHS / United States R01 CA077398 / CA / NCI NIH HHS / United States R01 CA077398-06 / CA / NCI NIH HHS / United States R01 CA122340 / CA / NCI NIH HHS / United States R01 CA122340-05 / CA / NCI NIH HHS / United States R01 CA77398 / CA / NCI NIH HHS / United States R25 CA092049 / CA / NCI NIH HHS / United States RFA-CA-06-503 / CA / NCI NIH HHS / United States U01 CA058860-08 / CA / NCI NIH HHS / United States U01 CA069417-06 / CA / NCI NIH HHS / United States U01 CA069638-14 / CA / NCI NIH HHS / United States U01 CA113916 / CA / NCI NIH HHS / United States U01 CA113916-07 / CA / NCI NIH HHS / United States U01 CA69417 / CA / NCI NIH HHS / United States U01 CA69467 / CA / NCI NIH HHS / United States U01 CA69631 / CA / NCI NIH HHS / United States U01 CA69638 / CA / NCI NIH HHS / United States |