Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

Roger L Milne; Ellen L Goode; Montserrat García-Closas; Fergus J Couch; Gianluca Severi; Rebecca Hein; Zachary Fredericksen; Núria Malats; M Pilar Zamora; Jose Ignacio Arias Pérez; Javier Benítez; Thilo Dörk; Peter Schürmann; Johann H Karstens; Peter Hillemanns; Angela Cox; Ian W Brock; Graeme Elliot; Simon S Cross; Sheila Seal; Clare Turnbull; Anthony Renwick; Nazneen Rahman; Chen-Yang Shen; Jyh-Cherng Yu; Chiun-Sheng Huang; Ming-Feng Hou; Børge G Nordestgaard; Stig E Bojesen; Charlotte Lanng; Grethe Grenaker Alnæs; Vessela Kristensen; Anne-Lise Børrensen-Dale; John L Hopper; Gillian S Dite; Carmel Apicella; Melissa C Southey; Diether Lambrechts; Betül T Yesilyurt; Giuseppe Floris; Karin Leunen; Suleeporn Sangrajrang; Valerie Gaborieau; Paul Brennan; James McKay; Jenny Chang-Claude; Shan Wang-Gohrke; Paolo Radice; Paolo Peterlongo; Siranoush Manoukian; for the GENICA Network

doi:10.1158/1055-9965.EPI-11-0569

Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

Roger L Milne, Ellen L Goode, Montserrat García-Closas, Fergus J Couch, Gianluca Severi, Rebecca Hein, Zachary Fredericksen, Núria Malats, M Pilar Zamora, Jose Ignacio Arias Pérez, Javier Benítez, Thilo Dörk, Peter Schürmann, Johann H Karstens, Peter Hillemanns, Angela Cox, Ian W Brock, Graeme Elliot, Simon S Cross, Sheila SealClare Turnbull, Anthony Renwick, Nazneen Rahman, Chen-Yang Shen, Jyh-Cherng Yu, Chiun-Sheng Huang, Ming-Feng Hou, Børge G Nordestgaard, Stig E Bojesen, Charlotte Lanng, Grethe Grenaker Alnæs, Vessela Kristensen, Anne-Lise Børrensen-Dale, John L Hopper, Gillian S Dite, Carmel Apicella, Melissa C Southey, Diether Lambrechts, Betül T Yesilyurt, Giuseppe Floris, Karin Leunen, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Jenny Chang-Claude, Shan Wang-Gohrke, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, for the GENICA Network

23 Citations (Scopus)

Abstract

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; Ptrend = 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.

Original language	English
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	20
Issue number	10
Pages (from-to)	2222-2231
Number of pages	10
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.EPI-11-0569
Publication status	Published - 1 Oct 2011

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10.1158/1055-9965.EPI-11-0569

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Milne, R. L., Goode, E. L., García-Closas, M., Couch, F. J., Severi, G., Hein, R., Fredericksen, Z., Malats, N., Zamora, M. P., Pérez, J. I. A., Benítez, J., Dörk, T., Schürmann, P., Karstens, J. H., Hillemanns, P., Cox, A., Brock, I. W., Elliot, G., Cross, S. S., ... for the GENICA Network (2011). Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer. Cancer Epidemiology, Biomarkers & Prevention, 20(10), 2222-2231. https://doi.org/10.1158/1055-9965.EPI-11-0569

Milne, RL, Goode, EL, García-Closas, M, Couch, FJ, Severi, G, Hein, R, Fredericksen, Z, Malats, N, Zamora, MP, Pérez, JIA, Benítez, J, Dörk, T, Schürmann, P, Karstens, JH, Hillemanns, P, Cox, A, Brock, IW, Elliot, G, Cross, SS, Seal, S, Turnbull, C, Renwick, A, Rahman, N, Shen, C-Y, Yu, J-C, Huang, C-S, Hou, M-F, Nordestgaard, BG , Bojesen, SE, Lanng, C, Alnæs, GG, Kristensen, V, Børrensen-Dale, A-L, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Lambrechts, D, Yesilyurt, BT, Floris, G, Leunen, K, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Chang-Claude, J, Wang-Gohrke, S, Radice, P, Peterlongo, P, Manoukian, S & for the GENICA Network 2011, 'Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer', Cancer Epidemiology, Biomarkers & Prevention, vol. 20, no. 10, pp. 2222-2231. https://doi.org/10.1158/1055-9965.EPI-11-0569

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title = "Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer",

abstract = "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; Pheterogeneity = 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; Ptrend = 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.",

author = "Milne, {Roger L} and Goode, {Ellen L} and Montserrat Garc{\'i}a-Closas and Couch, {Fergus J} and Gianluca Severi and Rebecca Hein and Zachary Fredericksen and N{\'u}ria Malats and Zamora, {M Pilar} and P{\'e}rez, {Jose Ignacio Arias} and Javier Ben{\'i}tez and Thilo D{\"o}rk and Peter Sch{\"u}rmann and Karstens, {Johann H} and Peter Hillemanns and Angela Cox and Brock, {Ian W} and Graeme Elliot and Cross, {Simon S} and Sheila Seal and Clare Turnbull and Anthony Renwick and Nazneen Rahman and Chen-Yang Shen and Jyh-Cherng Yu and Chiun-Sheng Huang and Ming-Feng Hou and Nordestgaard, {B{\o}rge G} and Bojesen, {Stig E} and Charlotte Lanng and Aln{\ae}s, {Grethe Grenaker} and Vessela Kristensen and Anne-Lise B{\o}rrensen-Dale and Hopper, {John L} and Dite, {Gillian S} and Carmel Apicella and Southey, {Melissa C} and Diether Lambrechts and Yesilyurt, {Bet{\"u}l T} and Giuseppe Floris and Karin Leunen and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James McKay and Jenny Chang-Claude and Shan Wang-Gohrke and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and B{\o}rge Nordestgaard",

year = "2011",

month = oct,

day = "1",

doi = "10.1158/1055-9965.EPI-11-0569",

language = "English",

volume = "20",

pages = "2222--2231",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research (A A C R)",

number = "10",

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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; Pheterogeneity = 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; Ptrend = 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.

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; Pheterogeneity = 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; Ptrend = 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.

U2 - 10.1158/1055-9965.EPI-11-0569

DO - 10.1158/1055-9965.EPI-11-0569

M3 - Journal article

SN - 1055-9965

VL - 20

SP - 2222

EP - 2231

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 10

ER -

Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer

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