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; 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; Stig E Bojesen; kConFab Investigators

doi:10.1002/ijc.29188

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 HallbergJ 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, Stig E Bojesen, kConFab Investigators

Institut for Klinisk Medicin

23 Citationer (Scopus)

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) <1.1 × 10^-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 <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10^-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.

Originalsprog	Engelsk
Tidsskrift	International Journal of Cancer
Vol/bind	136
Udgave nummer	6
Sider (fra-til)	E685-E696
Antal sider	12
ISSN	0020-7136
DOI	https://doi.org/10.1002/ijc.29188
Status	Udgivet - 15 mar. 2015

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Rudolph, A., Milne, R. L., Truong, T., Knight, J. A., Seibold, P., Flesch-Janys, D., Behrens, S., Eilber, U., Bolla, M. K., Wang, Q., Dennis, J., Dunning, A. M., Shah, M., Munday, H. R., Darabi, H., Eriksson, M., Brand, J. S., Olson, J., Vachon, C. M., ... kConFab Investigators (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

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, Arias Perez, JI, Provenzano, E, Apicella, C, Southey, MC, Spurdle, A, Häberle, L, Beckmann, MW, Ekici, AB, Bojesen, SE & kConFab Investigators 2015, 'Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors', International Journal of Cancer, bind 136, nr. 6, s. E685-E696. https://doi.org/10.1002/ijc.29188

@article{4509fc8e3df6431abd9940a46e25022d,

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

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) <1.1 × 10-3 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 <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10-4). 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.",

keywords = "Breast Neoplasms, Female, Gene-Environment Interaction, Genetic Loci, Genetic Predisposition to Disease, Humans, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Factors",

author = "Anja Rudolph and Milne, {Roger L} and Th{\'e}r{\`e}se Truong and Knight, {Julia A} and Petra Seibold and Dieter Flesch-Janys and Sabine Behrens and Ursula Eilber and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Dunning, {Alison M} and Mitul Shah and Munday, {Hannah R} and Hatef Darabi and Mikael Eriksson and Brand, {Judith S} and Janet Olson and Vachon, {Celine M} and Emily Hallberg and Castelao, {J Esteban} and Angel Carracedo and Maria Torres and Jingmei Li and Keith Humphreys and Emilie Cordina-Duverger and Florence Menegaux and Henrik Flyger and Nordestgaard, {B{\o}rge G} and Nielsen, {Sune F} and Yesilyurt, {Betul T} and Giuseppe Floris and Karin Leunen and Engelhardt, {Ellen G} and Annegien Broeks and Rutgers, {Emiel J} and Gord Glendon and Mulligan, {Anna Marie} and Simon Cross and Malcolm Reed and Anna Gonzalez-Neira and {Arias Perez}, {Jos{\'e} Ignacio} and Elena Provenzano and Carmel Apicella and Southey, {Melissa C} and Amanda Spurdle and Lothar H{\"a}berle and Beckmann, {Matthias W} and Ekici, {Arif B} and Bojesen, {Stig E} and {kConFab Investigators}",

note = "{\textcopyright} 2014 UICC.",

year = "2015",

month = mar,

day = "15",

doi = "10.1002/ijc.29188",

language = "English",

volume = "136",

pages = "E685--E696",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "JohnWiley & Sons, Inc.",

number = "6",

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TY - JOUR

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 - Arias Perez, José Ignacio

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 - Bojesen, Stig E

AU - kConFab Investigators

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) <1.1 × 10-3 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 <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10-4). 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) <1.1 × 10-3 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 <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10-4). 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 Neoplasms

KW - Female

KW - Gene-Environment Interaction

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Humans

KW - Polymorphism, Single Nucleotide

KW - Receptors, Estrogen

KW - Risk Factors

U2 - 10.1002/ijc.29188

DO - 10.1002/ijc.29188

M3 - Journal article

C2 - 25227710

SN - 0020-7136

VL - 136

SP - E685-E696

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 6

ER -

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

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