TY  - JOUR
AU  - Wang, Xiaoliang
AU  - Chen, Hongjie
AU  - Middha Kapoor, Pooja
AU  - Su, Yu-Ru
AU  - Bolla, Manjeet K
AU  - Dennis, Joe
AU  - Dunning, Alison M
AU  - Lush, Michael
AU  - Wang, Qin
AU  - Michailidou, Kyriaki
AU  - Pharoah, Paul D P
AU  - Hopper, John L
AU  - Southey, Melissa C
AU  - Koutros, Stella
AU  - Beane Freeman, Laura E
AU  - Stone, Jennifer
AU  - Rennert, Gad
AU  - Shibli, Rana
AU  - Murphy, Rachel A
AU  - Aronson, Kristan
AU  - Guénel, Pascal
AU  - Truong, Thérèse
AU  - Teras, Lauren R
AU  - Hodge, James M
AU  - Canzian, Federico
AU  - Kaaks, Rudolf
AU  - Brenner, Hermann
AU  - Arndt, Volker
AU  - Hoppe, Reiner
AU  - Lo, Wing-Yee
AU  - Behrens, Sabine
AU  - Mannermaa, Arto
AU  - Kosma, Veli-Matti
AU  - Jung, Audrey Ying-Chee
AU  - Becher, Heiko
AU  - Giles, Graham G
AU  - Haiman, Christopher A
AU  - Maskarinec, Gertraud
AU  - Scott, Christopher
AU  - Winham, Stacey
AU  - Simard, Jacques
AU  - Goldberg, Mark S
AU  - Zheng, Wei
AU  - Long, Jirong
AU  - Troester, Melissa A
AU  - Love, Michael I
AU  - Peng, Cheng
AU  - Tamimi, Rulla
AU  - Eliassen, Heather
AU  - García-Closas, Montserrat
AU  - Figueroa, Jonine
AU  - Ahearn, Thomas
AU  - Yang, Rose
AU  - Evans, D Gareth
AU  - Howell, Anthony
AU  - Hall, Per
AU  - Czene, Kamila
AU  - Wolk, Alicja
AU  - Sandler, Dale P
AU  - Taylor, Jack A
AU  - Swerdlow, Anthony J
AU  - Orr, Nick
AU  - Lacey, James V
AU  - Wang, Sophia
AU  - Olsson, Håkan
AU  - Easton, Douglas F
AU  - Milne, Roger L
AU  - Hsu, Li
AU  - Kraft, Peter
AU  - Chang-Claude, Jenny
AU  - Lindström, Sara
TI  - A genome-wide gene-based gene-environment interaction study of breast cancer in more than 90,000 women.
JO  - Cancer research communications
VL  - 2
IS  - 4
SN  - 2767-9764
CY  - Philadelphia, Pa.
PB  - American Association for Cancer Research
M1  - DKFZ-2022-02582
SP  - 211 - 219
PY  - 2022
AB  - Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene-environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this.We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P<0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test.After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE=4.44×10-6).In this transcriptome-informed genome-wide gene-environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk.Our study suggests a limited role of gene-environment interactions in breast cancer risk.
LB  - PUB:(DE-HGF)16
C6  - pmid:36303815
C2  - pmc:PMC9604427
DO  - DOI:10.1158/2767-9764.CRC-21-0119
UR  - https://inrepo02.dkfz.de/record/182339
ER  -