TY - JOUR
T1 - Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer
AU - Milne, Roger L
AU - Goode, Ellen L
AU - García-Closas, Montserrat
AU - Couch, Fergus J
AU - Severi, Gianluca
AU - Hein, Rebecca
AU - Fredericksen, Zachary
AU - Malats, Núria
AU - Zamora, M Pilar
AU - Pérez, Jose Ignacio Arias
AU - Benítez, Javier
AU - Dörk, Thilo
AU - Schürmann, Peter
AU - Karstens, Johann H
AU - Hillemanns, Peter
AU - Cox, Angela
AU - Brock, Ian W
AU - Elliot, Graeme
AU - Cross, Simon S
AU - Seal, Sheila
AU - Turnbull, Clare
AU - Renwick, Anthony
AU - Rahman, Nazneen
AU - Shen, Chen-Yang
AU - Yu, Jyh-Cherng
AU - Huang, Chiun-Sheng
AU - Hou, Ming-Feng
AU - Nordestgaard, Børge G
AU - Bojesen, Stig E
AU - Lanng, Charlotte
AU - Alnæs, Grethe Grenaker
AU - Kristensen, Vessela
AU - Børrensen-Dale, Anne-Lise
AU - Hopper, John L
AU - Dite, Gillian S
AU - Apicella, Carmel
AU - Southey, Melissa C
AU - Lambrechts, Diether
AU - Yesilyurt, Betül T
AU - Floris, Giuseppe
AU - Leunen, Karin
AU - Sangrajrang, Suleeporn
AU - Gaborieau, Valerie
AU - Brennan, Paul
AU - McKay, James
AU - Chang-Claude, Jenny
AU - Wang-Gohrke, Shan
AU - Radice, Paolo
AU - Peterlongo, Paolo
AU - Manoukian, Siranoush
AU - for the GENICA Network
PY - 2011/10/1
Y1 - 2011/10/1
N2 - BACKGROUND: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. METHODS: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. RESULTS: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) = 2 × 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; P(trend) = 5 × 10(-7)]. CONCLUSION: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222-31. ©2011 AACR.
AB - BACKGROUND: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. METHODS: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. RESULTS: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) = 2 × 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; P(trend) = 5 × 10(-7)]. CONCLUSION: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. Cancer Epidemiol Biomarkers Prev; 20(10); 2222-31. ©2011 AACR.
U2 - http://dx.doi.org/10.1158/1055-9965.EPI-11-0569
DO - http://dx.doi.org/10.1158/1055-9965.EPI-11-0569
M3 - Journal article
VL - 20
SP - 2222
EP - 2231
JO - Cancer Epidemiology, Biomarkers & Prevention
JF - Cancer Epidemiology, Biomarkers & Prevention
SN - 1055-9965
IS - 10
ER -