A genome-wide gene-based gene-environment interaction study of breast cancer in more than 90,000 women

A genome-wide gene-based gene-environment interaction study of breast cancer in more than 90,000 women. Wang, X., Chen, H., Middha Kapoor, P., Su, Y., Bolla, M. K., Dennis, J., Dunning, A. M., Lush, M., Wang, Q., Michailidou, K., Pharoah, P. D. P., Hopper, J. L., Southey, M. C., Koutros, S., Beane Freeman, L. E., Stone, J., Rennert, G., Shibli, R., Murphy, R. A., Aronson, K., Guénel, P., Truong, T., Teras, L. R., Hodge, J. M., Canzian, F., Kaaks, R., Brenner, H., Arndt, V., Hoppe, R., Lo, W., Behrens, S., Mannermaa, A., Kosma, V., Jung, A., Becher, H., Giles, G. G., Haiman, C. A., Maskarinec, G., Scott, C., Winham, S., Simard, J., Goldberg, M. S., Zheng, W., Long, J., Troester, M. A., Love, M. I., Peng, C., Tamimi, R., Eliassen, H., García-Closas, M., Figueroa, J., Ahearn, T., Yang, R., Evans, D. G., Howell, A., Hall, P., Czene, K., Wolk, A., Sandler, D. P., Taylor, J. A., Swerdlow, A. J., Orr, N., Lacey, J. V., Wang, S., Olsson, H., Easton, D. F., Milne, R. L., Hsu, L., Kraft, P., Chang-Claude, J., & Lindström, S. Cancer Research Communications, 2(4):211–219, April, 2022.
doi abstract bibtex

BACKGROUND: 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. METHODS: 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\textless0.01) 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. RESULTS: 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). CONCLUSION: 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. IMPACT: Our study suggests a limited role of gene-environment interactions in breast cancer risk.

@article{wang_genome-wide_2022-1,
	title = {A genome-wide gene-based gene-environment interaction study of breast cancer in more than 90,000 women},
	volume = {2},
	issn = {2767-9764},
	doi = {10.1158/2767-9764.CRC-21-0119},
	abstract = {BACKGROUND: 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.
METHODS: 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{\textless}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.
RESULTS: 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).
CONCLUSION: 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.
IMPACT: Our study suggests a limited role of gene-environment interactions in breast cancer risk.},
	language = {eng},
	number = {4},
	journal = {Cancer Research Communications},
	author = {Wang, Xiaoliang and Chen, Hongjie and Middha Kapoor, Pooja and Su, Yu-Ru and Bolla, Manjeet K. and Dennis, Joe and Dunning, Alison M. and Lush, Michael and Wang, Qin and Michailidou, Kyriaki and Pharoah, Paul D. P. and Hopper, John L. and Southey, Melissa C. and Koutros, Stella and Beane Freeman, Laura E. and Stone, Jennifer and Rennert, Gad and Shibli, Rana and Murphy, Rachel A. and Aronson, Kristan and Guénel, Pascal and Truong, Thérèse and Teras, Lauren R. and Hodge, James M. and Canzian, Federico and Kaaks, Rudolf and Brenner, Hermann and Arndt, Volker and Hoppe, Reiner and Lo, Wing-Yee and Behrens, Sabine and Mannermaa, Arto and Kosma, Veli-Matti and Jung, Audrey and Becher, Heiko and Giles, Graham G. and Haiman, Christopher A. and Maskarinec, Gertraud and Scott, Christopher and Winham, Stacey and Simard, Jacques and Goldberg, Mark S. and Zheng, Wei and Long, Jirong and Troester, Melissa A. and Love, Michael I. and Peng, Cheng and Tamimi, Rulla and Eliassen, Heather and García-Closas, Montserrat and Figueroa, Jonine and Ahearn, Thomas and Yang, Rose and Evans, D. Gareth and Howell, Anthony and Hall, Per and Czene, Kamila and Wolk, Alicja and Sandler, Dale P. and Taylor, Jack A. and Swerdlow, Anthony J. and Orr, Nick and Lacey, James V. and Wang, Sophia and Olsson, Håkan and Easton, Douglas F. and Milne, Roger L. and Hsu, Li and Kraft, Peter and Chang-Claude, Jenny and Lindström, Sara},
	month = apr,
	year = {2022},
	pmid = {36303815},
	pmcid = {PMC9604427},
	keywords = {Breast Neoplasms, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Risk Factors},
	pages = {211--219},
}

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