Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

Anja Rudolph, Roger L. Milne, Thérèse Truong, Julia A. Knight, Petra Seibold, Dieter Flesch-Janys, Sabine Behrens, Ursula Eilber, Manjeet K. Bolla, Qin Wang, Joe Dennis, Alison M. Dunning, Mitul Shah, Hannah R. Munday, Hatef Darabi, Mikael Eriksson, Judith S. Brand, Janet Olson, Celine M. Vachon, Emily Hallberg & 68 others J. Esteban Castelao, Angel Carracedo, Maria Torres, Jingmei Li, Keith Humphreys, Emilie Cordina-Duverger, Florence Menegaux, Henrik Flyger, Børge G. Nordestgaard, Sune F. Nielsen, Betul T. Yesilyurt, Giuseppe Floris, Karin Leunen, Ellen G. Engelhardt, Annegien Broeks, Emiel J. Rutgers, Gord Glendon, Anna Marie Mulligan, Simon Cross, Malcolm Reed, Anna Gonzalez-Neira, José Ignacio Arias Perez, Elena Provenzano, Carmel Apicella, Melissa C. Southey, Amanda Spurdle, Lothar Häberle, Matthias W. Beckmann, Arif B. Ekici, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Catriona McLean, Laura Baglietto, Stephen J. Chanock, Jolanta Lissowska, Mark E. Sherman, Thomas Brüning, Ute Hamann, Yon Dschun Ko, Nick Orr, Minouk Schoemaker, Alan Ashworth, Veli Matti Kosma, Vesa Kataja, Jaana M. Hartikainen, Arto Mannermaa, Anthony Swerdlow, Graham G. Giles, Hermann Brenner, Peter A. Fasching, Georgia Chenevix-Trench, John Hopper, Javier Benítez, Angela Cox, Irene L. Andrulis, Diether Lambrechts, Manuela Gago-Dominguez, Fergus Couch, Kamila Czene, Stig E. Bojesen, Doug F. Easton, Marjanka K. Schmidt, Pascal Guénel, Per Hall, Paul D P Pharoah, Montserrat Garcia-Closas, Jenny Chang-Claude

Research output: Contribution to journalArticle

Abstract

A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint) -3 None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women -4). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10-4), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10-4). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10-5), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10-4). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

Original languageEnglish (US)
Pages (from-to)E685-E696
JournalInternational Journal of Cancer
Volume136
Issue number6
DOIs
StatePublished - Mar 15 2015
Externally publishedYes

Fingerprint

Gene-Environment Interaction
Breast Neoplasms
Single Nucleotide Polymorphism
Estrogen Receptors
Pregnancy

Keywords

  • Breast cancer
  • Gene-environment interaction
  • Genetic susceptibility
  • Risk factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rudolph, A., Milne, R. L., Truong, T., Knight, J. A., Seibold, P., Flesch-Janys, D., ... Chang-Claude, J. (2015). Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors. International Journal of Cancer, 136(6), E685-E696. https://doi.org/10.1002/ijc.29188

Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors. / Rudolph, Anja; Milne, Roger L.; Truong, Thérèse; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Munday, Hannah R.; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Olson, Janet; Vachon, Celine M.; Hallberg, Emily; Castelao, J. Esteban; Carracedo, Angel; Torres, Maria; Li, Jingmei; Humphreys, Keith; Cordina-Duverger, Emilie; Menegaux, Florence; Flyger, Henrik; Nordestgaard, Børge G.; Nielsen, Sune F.; Yesilyurt, Betul T.; Floris, Giuseppe; Leunen, Karin; Engelhardt, Ellen G.; Broeks, Annegien; Rutgers, Emiel J.; Glendon, Gord; Mulligan, Anna Marie; Cross, Simon; Reed, Malcolm; Gonzalez-Neira, Anna; Perez, José Ignacio Arias; Provenzano, Elena; Apicella, Carmel; Southey, Melissa C.; Spurdle, Amanda; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; McLean, Catriona; Baglietto, Laura; Chanock, Stephen J.; Lissowska, Jolanta; Sherman, Mark E.; Brüning, Thomas; Hamann, Ute; Ko, Yon Dschun; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Kosma, Veli Matti; Kataja, Vesa; Hartikainen, Jaana M.; Mannermaa, Arto; Swerdlow, Anthony; Giles, Graham G.; Brenner, Hermann; Fasching, Peter A.; Chenevix-Trench, Georgia; Hopper, John; Benítez, Javier; Cox, Angela; Andrulis, Irene L.; Lambrechts, Diether; Gago-Dominguez, Manuela; Couch, Fergus; Czene, Kamila; Bojesen, Stig E.; Easton, Doug F.; Schmidt, Marjanka K.; Guénel, Pascal; Hall, Per; Pharoah, Paul D P; Garcia-Closas, Montserrat; Chang-Claude, Jenny.

In: International Journal of Cancer, Vol. 136, No. 6, 15.03.2015, p. E685-E696.

Research output: Contribution to journalArticle

Rudolph, A, Milne, RL, Truong, T, Knight, JA, Seibold, P, Flesch-Janys, D, Behrens, S, Eilber, U, Bolla, MK, Wang, Q, Dennis, J, Dunning, AM, Shah, M, Munday, HR, Darabi, H, Eriksson, M, Brand, JS, Olson, J, Vachon, CM, Hallberg, E, Castelao, JE, Carracedo, A, Torres, M, Li, J, Humphreys, K, Cordina-Duverger, E, Menegaux, F, Flyger, H, Nordestgaard, BG, Nielsen, SF, Yesilyurt, BT, Floris, G, Leunen, K, Engelhardt, EG, Broeks, A, Rutgers, EJ, Glendon, G, Mulligan, AM, Cross, S, Reed, M, Gonzalez-Neira, A, Perez, JIA, Provenzano, E, Apicella, C, Southey, MC, Spurdle, A, Häberle, L, Beckmann, MW, Ekici, AB, Dieffenbach, AK, Arndt, V, Stegmaier, C, McLean, C, Baglietto, L, Chanock, SJ, Lissowska, J, Sherman, ME, Brüning, T, Hamann, U, Ko, YD, Orr, N, Schoemaker, M, Ashworth, A, Kosma, VM, Kataja, V, Hartikainen, JM, Mannermaa, A, Swerdlow, A, Giles, GG, Brenner, H, Fasching, PA, Chenevix-Trench, G, Hopper, J, Benítez, J, Cox, A, Andrulis, IL, Lambrechts, D, Gago-Dominguez, M, Couch, F, Czene, K, Bojesen, SE, Easton, DF, Schmidt, MK, Guénel, P, Hall, P, Pharoah, PDP, Garcia-Closas, M & Chang-Claude, J 2015, 'Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors', International Journal of Cancer, vol. 136, no. 6, pp. E685-E696. https://doi.org/10.1002/ijc.29188
Rudolph, Anja ; Milne, Roger L. ; Truong, Thérèse ; Knight, Julia A. ; Seibold, Petra ; Flesch-Janys, Dieter ; Behrens, Sabine ; Eilber, Ursula ; Bolla, Manjeet K. ; Wang, Qin ; Dennis, Joe ; Dunning, Alison M. ; Shah, Mitul ; Munday, Hannah R. ; Darabi, Hatef ; Eriksson, Mikael ; Brand, Judith S. ; Olson, Janet ; Vachon, Celine M. ; Hallberg, Emily ; Castelao, J. Esteban ; Carracedo, Angel ; Torres, Maria ; Li, Jingmei ; Humphreys, Keith ; Cordina-Duverger, Emilie ; Menegaux, Florence ; Flyger, Henrik ; Nordestgaard, Børge G. ; Nielsen, Sune F. ; Yesilyurt, Betul T. ; Floris, Giuseppe ; Leunen, Karin ; Engelhardt, Ellen G. ; Broeks, Annegien ; Rutgers, Emiel J. ; Glendon, Gord ; Mulligan, Anna Marie ; Cross, Simon ; Reed, Malcolm ; Gonzalez-Neira, Anna ; Perez, José Ignacio Arias ; Provenzano, Elena ; Apicella, Carmel ; Southey, Melissa C. ; Spurdle, Amanda ; Häberle, Lothar ; Beckmann, Matthias W. ; Ekici, Arif B. ; Dieffenbach, Aida Karina ; Arndt, Volker ; Stegmaier, Christa ; McLean, Catriona ; Baglietto, Laura ; Chanock, Stephen J. ; Lissowska, Jolanta ; Sherman, Mark E. ; Brüning, Thomas ; Hamann, Ute ; Ko, Yon Dschun ; Orr, Nick ; Schoemaker, Minouk ; Ashworth, Alan ; Kosma, Veli Matti ; Kataja, Vesa ; Hartikainen, Jaana M. ; Mannermaa, Arto ; Swerdlow, Anthony ; Giles, Graham G. ; Brenner, Hermann ; Fasching, Peter A. ; Chenevix-Trench, Georgia ; Hopper, John ; Benítez, Javier ; Cox, Angela ; Andrulis, Irene L. ; Lambrechts, Diether ; Gago-Dominguez, Manuela ; Couch, Fergus ; Czene, Kamila ; Bojesen, Stig E. ; Easton, Doug F. ; Schmidt, Marjanka K. ; Guénel, Pascal ; Hall, Per ; Pharoah, Paul D P ; Garcia-Closas, Montserrat ; Chang-Claude, Jenny. / Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors. In: International Journal of Cancer. 2015 ; Vol. 136, No. 6. pp. E685-E696.
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T1 - Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

AU - Rudolph, Anja

AU - Milne, Roger L.

AU - Truong, Thérèse

AU - Knight, Julia A.

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Behrens, Sabine

AU - Eilber, Ursula

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Dunning, Alison M.

AU - Shah, Mitul

AU - Munday, Hannah R.

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Brand, Judith S.

AU - Olson, Janet

AU - Vachon, Celine M.

AU - Hallberg, Emily

AU - Castelao, J. Esteban

AU - Carracedo, Angel

AU - Torres, Maria

AU - Li, Jingmei

AU - Humphreys, Keith

AU - Cordina-Duverger, Emilie

AU - Menegaux, Florence

AU - Flyger, Henrik

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Yesilyurt, Betul T.

AU - Floris, Giuseppe

AU - Leunen, Karin

AU - Engelhardt, Ellen G.

AU - Broeks, Annegien

AU - Rutgers, Emiel J.

AU - Glendon, Gord

AU - Mulligan, Anna Marie

AU - Cross, Simon

AU - Reed, Malcolm

AU - Gonzalez-Neira, Anna

AU - Perez, José Ignacio Arias

AU - Provenzano, Elena

AU - Apicella, Carmel

AU - Southey, Melissa C.

AU - Spurdle, Amanda

AU - Häberle, Lothar

AU - Beckmann, Matthias W.

AU - Ekici, Arif B.

AU - Dieffenbach, Aida Karina

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - McLean, Catriona

AU - Baglietto, Laura

AU - Chanock, Stephen J.

AU - Lissowska, Jolanta

AU - Sherman, Mark E.

AU - Brüning, Thomas

AU - Hamann, Ute

AU - Ko, Yon Dschun

AU - Orr, Nick

AU - Schoemaker, Minouk

AU - Ashworth, Alan

AU - Kosma, Veli Matti

AU - Kataja, Vesa

AU - Hartikainen, Jaana M.

AU - Mannermaa, Arto

AU - Swerdlow, Anthony

AU - Giles, Graham G.

AU - Brenner, Hermann

AU - Fasching, Peter A.

AU - Chenevix-Trench, Georgia

AU - Hopper, John

AU - Benítez, Javier

AU - Cox, Angela

AU - Andrulis, Irene L.

AU - Lambrechts, Diether

AU - Gago-Dominguez, Manuela

AU - Couch, Fergus

AU - Czene, Kamila

AU - Bojesen, Stig E.

AU - Easton, Doug F.

AU - Schmidt, Marjanka K.

AU - Guénel, Pascal

AU - Hall, Per

AU - Pharoah, Paul D P

AU - Garcia-Closas, Montserrat

AU - Chang-Claude, Jenny

PY - 2015/3/15

Y1 - 2015/3/15

N2 - A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint) -3 None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women -4). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10-4), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10-4). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10-5), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10-4). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

AB - A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint) -3 None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women -4). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10-4), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10-4). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10-5), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10-4). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

KW - Breast cancer

KW - Gene-environment interaction

KW - Genetic susceptibility

KW - Risk factor

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DO - 10.1002/ijc.29188

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JO - International Journal of Cancer

JF - International Journal of Cancer

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