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 ERnegative 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1795-1803 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 72 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 1 Apr 2012 |
| Externally published | Yes |
Cite this
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19p13.1 Is a triple-negative-specific breast cancer susceptibility locus. / Stevens, Kristen N.; Fredericksen, Zachary; Vachon, Celine M; Wang, Xianshu; Margolin, Sara; Lindblom, Annika; Nevanlinna, Heli; Greco, Dario; Aittomak̈i, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Vrieling, Alina; Flesch-Janys, Dieter; Sinn, Hans Peter; Wang-Gohrke, Shan; Nickels, Stefan; Brauch, Hiltrud; Ko, Yon-Dschun; Fischer, Hans-Peter; Schmutzler, Rita K.; Hopper, John L.; Southey, Melissa C.; Giles, Graham G.; McLean, Catriona A.
In: Cancer Research, Vol. 72, No. 7, 01.04.2012, p. 1795-1803.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - 19p13.1 Is a triple-negative-specific breast cancer susceptibility locus
AU - Stevens, Kristen N.
AU - Fredericksen, Zachary
AU - Vachon, Celine M
AU - Wang, Xianshu
AU - Margolin, Sara
AU - Lindblom, Annika
AU - Nevanlinna, Heli
AU - Greco, Dario
AU - Aittomak̈i, Kristiina
AU - Blomqvist, Carl
AU - Chang-Claude, Jenny
AU - Vrieling, Alina
AU - Flesch-Janys, Dieter
AU - Sinn, Hans Peter
AU - Wang-Gohrke, Shan
AU - Nickels, Stefan
AU - Brauch, Hiltrud
AU - Ko, Yon-Dschun
AU - Fischer, Hans-Peter
AU - Schmutzler, Rita K.
AU - Hopper, John L.
AU - Southey, Melissa C.
AU - Giles, Graham G.
AU - McLean, Catriona A.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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 ERnegative 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.
AB - 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 ERnegative 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.
UR - http://www.scopus.com/inward/record.url?scp=84859375225&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-11-3364
DO - 10.1158/0008-5472.CAN-11-3364
M3 - Article
VL - 72
SP - 1795
EP - 1803
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 7
ER -