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

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

15 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 (P(het)) = 1.3 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 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; P(het) = 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 the G allele 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
Pages (from-to)	1783-91
Number of pages	9
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	21
Issue number	10
DOIs	https://doi.org/10.1158/1055-9965.EPI-12-0526
Publication status	Published - Oct 2012

Keywords

Aged
Breast Neoplasms
Case-Control Studies
Chromosome Mapping
Chromosomes, Human, Pair 9
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Middle Aged
Polymorphism, Single Nucleotide
Receptors, Estrogen
Receptors, Progesterone
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

@article{a69c8d9e2ca844c6857059220d7d9c63,

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 (P(het)) = 1.3 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 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; P(het) = 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 the G allele 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.",

keywords = "Aged, Breast Neoplasms, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 9, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Estrogen, Receptors, Progesterone, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.",

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 {GENICA Network}",

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 Inc.",

number = "10",

}

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

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 (P(het)) = 1.3 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 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; P(het) = 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 the G allele 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 (P(het)) = 1.3 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 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; P(het) = 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 the G allele 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.

KW - Aged

KW - Breast Neoplasms

KW - Case-Control Studies

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 9

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Receptors, Estrogen

KW - Receptors, Progesterone

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

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

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

M3 - 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

Abstract

Keywords

UN SDGs

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