9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium

Helen Warren; Frank Dudbridge; Olivia Fletcher; Nick Orr; Nichola Johnson; John L Hopper; Carmel Apicella; Melissa C Southey; Maryam Mahmoodi; Marjanka K Schmidt; Annegien Broeks; Sten Cornelissen; Linda M Braaf; Kenneth R Muir; Artitaya Lophatananon; Arkom Chaiwerawattana; Surapon Wiangnon; Peter A Fasching; Matthias W Beckmann; Arif B Ekici; Ruediger Schulz-Wendtland; Elinor J Sawyer; Ian Tomlinson; Michael Kerin; Barbara Burwinkel; Frederik Marme; Andreas Schneeweiss; Christof Sohn; Pascal Guénel; Thérèse Truong; Pierre Laurent-Puig; Claire Mulot; Stig E Bojesen; Sune F Nielsen; Henrik Flyger; Børge G Nordestgaard; Roger L Milne; Javier Benítez; José-Ignacio Arias-Pérez; M Pilar Zamora; Hoda Anton-Culver; Argyrios Ziogas; Leslie Bernstein; Christina Clarke Dur; Hermann Brenner; Heiko Müller; Volker Arndt; Anne Langheinz; Alfons Meindl; Michael Golatta; GENICA Network

doi:10.1158/1055-9965.EPI-12-0526

9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium

Helen Warren, Frank Dudbridge, Olivia Fletcher, Nick Orr, Nichola Johnson, John L Hopper, Carmel Apicella, Melissa C Southey, Maryam Mahmoodi, Marjanka K Schmidt, Annegien Broeks, Sten Cornelissen, Linda M Braaf, Kenneth R Muir, Artitaya Lophatananon, Arkom Chaiwerawattana, Surapon Wiangnon, Peter A Fasching, Matthias W Beckmann, Arif B EkiciRuediger Schulz-Wendtland, Elinor J Sawyer, Ian Tomlinson, Michael Kerin, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Pascal Guénel, Thérèse Truong, Pierre Laurent-Puig, Claire Mulot, Stig E Bojesen, Sune F Nielsen, Henrik Flyger, Børge G Nordestgaard, Roger L Milne, Javier Benítez, José-Ignacio Arias-Pérez, M Pilar Zamora, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina Clarke Dur, Hermann Brenner, Heiko Müller, Volker Arndt, Anne Langheinz, Alfons Meindl, Michael Golatta, GENICA Network

14 Citations (Scopus)

Abstract

Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P =2.01 × 10-29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10-143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10-22) but less strongly, if at all, with ER-negative (ER+) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; Phet = 1.16 × 10-6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of theGallele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype.

Original language	English
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	21
Issue number	10
Pages (from-to)	1783-91
Number of pages	9
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.EPI-12-0526
Publication status	Published - Oct 2012

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10.1158/1055-9965.EPI-12-0526

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Warren, H., Dudbridge, F., Fletcher, O., Orr, N., Johnson, N., Hopper, J. L., Apicella, C., Southey, M. C., Mahmoodi, M., Schmidt, M. K., Broeks, A., Cornelissen, S., Braaf, L. M., Muir, K. R., Lophatananon, A., Chaiwerawattana, A., Wiangnon, S., Fasching, P. A., Beckmann, M. W., ... GENICA Network (2012). 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium. Cancer Epidemiology, Biomarkers & Prevention, 21(10), 1783-91. https://doi.org/10.1158/1055-9965.EPI-12-0526

9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer : evidence from the Breast Cancer Association Consortium. / Warren, Helen; Dudbridge, Frank; Fletcher, Olivia et al.

In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 21, No. 10, 10.2012, p. 1783-91.

Research output: Contribution to journal › Journal article › Research › peer-review

Warren, H, Dudbridge, F, Fletcher, O, Orr, N, Johnson, N, Hopper, JL, Apicella, C, Southey, MC, Mahmoodi, M, Schmidt, MK, Broeks, A, Cornelissen, S, Braaf, LM, Muir, KR, Lophatananon, A, Chaiwerawattana, A, Wiangnon, S, Fasching, PA, Beckmann, MW, Ekici, AB, Schulz-Wendtland, R, Sawyer, EJ, Tomlinson, I, Kerin, M, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Guénel, P, Truong, T, Laurent-Puig, P, Mulot, C, Bojesen, SE, Nielsen, SF, Flyger, H, Nordestgaard, BG, Milne, RL, Benítez, J, Arias-Pérez, J-I, Zamora, MP, Anton-Culver, H, Ziogas, A, Bernstein, L, Dur, CC, Brenner, H, Müller, H, Arndt, V, Langheinz, A, Meindl, A, Golatta, M & GENICA Network 2012, '9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium', Cancer Epidemiology, Biomarkers & Prevention, vol. 21, no. 10, pp. 1783-91. https://doi.org/10.1158/1055-9965.EPI-12-0526

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title = "9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium",

abstract = "Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P =2.01 × 10-29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10-143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10-22) but less strongly, if at all, with ER-negative (ER+) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; Phet = 1.16 × 10-6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of theGallele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype.",

author = "Helen Warren and Frank Dudbridge and Olivia Fletcher and Nick Orr and Nichola Johnson and Hopper, {John L} and Carmel Apicella and Southey, {Melissa C} and Maryam Mahmoodi and Schmidt, {Marjanka K} and Annegien Broeks and Sten Cornelissen and Braaf, {Linda M} and Muir, {Kenneth R} and Artitaya Lophatananon and Arkom Chaiwerawattana and Surapon Wiangnon and Fasching, {Peter A} and Beckmann, {Matthias W} and Ekici, {Arif B} and Ruediger Schulz-Wendtland and Sawyer, {Elinor J} and Ian Tomlinson and Michael Kerin and Barbara Burwinkel and Frederik Marme and Andreas Schneeweiss and Christof Sohn and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Pierre Laurent-Puig and Claire Mulot and Bojesen, {Stig E} and Nielsen, {Sune F} and Henrik Flyger and Nordestgaard, {B{\o}rge G} and Milne, {Roger L} and Javier Ben{\'i}tez and Jos{\'e}-Ignacio Arias-P{\'e}rez and Zamora, {M Pilar} and Hoda Anton-Culver and Argyrios Ziogas and Leslie Bernstein and Dur, {Christina Clarke} and Hermann Brenner and Heiko M{\"u}ller and Volker Arndt and Anne Langheinz and Alfons Meindl and Michael Golatta and B{\o}rge Nordestgaard",

note = "2012 AACR",

year = "2012",

month = oct,

doi = "10.1158/1055-9965.EPI-12-0526",

language = "English",

volume = "21",

pages = "1783--91",

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 - 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer

T2 - evidence from the Breast Cancer Association Consortium

AU - Warren, Helen

AU - Dudbridge, Frank

AU - Fletcher, Olivia

AU - Orr, Nick

AU - Johnson, Nichola

AU - Hopper, John L

AU - Apicella, Carmel

AU - Southey, Melissa C

AU - Mahmoodi, Maryam

AU - Schmidt, Marjanka K

AU - Broeks, Annegien

AU - Cornelissen, Sten

AU - Braaf, Linda M

AU - Muir, Kenneth R

AU - Lophatananon, Artitaya

AU - Chaiwerawattana, Arkom

AU - Wiangnon, Surapon

AU - Fasching, Peter A

AU - Beckmann, Matthias W

AU - Ekici, Arif B

AU - Schulz-Wendtland, Ruediger

AU - Sawyer, Elinor J

AU - Tomlinson, Ian

AU - Kerin, Michael

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Laurent-Puig, Pierre

AU - Mulot, Claire

AU - Bojesen, Stig E

AU - Nielsen, Sune F

AU - Flyger, Henrik

AU - Nordestgaard, Børge G

AU - Milne, Roger L

AU - Benítez, Javier

AU - Arias-Pérez, José-Ignacio

AU - Zamora, M Pilar

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Bernstein, Leslie

AU - Dur, Christina Clarke

AU - Brenner, Hermann

AU - Müller, Heiko

AU - Arndt, Volker

AU - Langheinz, Anne

AU - Meindl, Alfons

AU - Golatta, Michael

AU - GENICA Network

N1 - 2012 AACR

PY - 2012/10

Y1 - 2012/10

N2 - Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P =2.01 × 10-29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10-143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10-22) but less strongly, if at all, with ER-negative (ER+) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; Phet = 1.16 × 10-6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of theGallele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype.

AB - Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P =2.01 × 10-29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10-143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10-22) but less strongly, if at all, with ER-negative (ER+) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; Phet = 1.16 × 10-6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of theGallele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype.

U2 - 10.1158/1055-9965.EPI-12-0526

DO - 10.1158/1055-9965.EPI-12-0526

M3 - Journal article

C2 - 22859399

SN - 1055-9965

VL - 21

SP - 1783

EP - 1791

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 10

ER -

9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium

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