Citations 12
Rare Copy Number Variants (CNVs) and Breast Cancer Risk
Dorling, Leila , Bola, Manjeet, Wang, Qin , Andrulis, Irene L. , Antonenkova, Natalia, Aronson, Kristan J. , Freeman, Laura Beane, Beckmann, Matthias W. , Bojeson, Stig, Chang‐Claude, Jenny , Chenevix‐Trench, Georgia , Collaborators, NBCS, Collée, J. Margriet, Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, Hahen, Eric, Haiman, Christopher A. , Hoppe, Reine, Investigators, ACTB, Investigators, kConFab, Jager, Agnes , Johnson, Nichola , Keeman, Renske , Ko, Yon‐Dschun, Kosma, Veli‐Matti , Kristensen, Vessela N. , Kubelka‐Sabit, Katerina , Kurian, Alison, Larson, Nicole L. , Linet, Martha S. , Łukomska, Alicja, Mannermaa, Arto , Mavroudis, Dimitrios, Park‐Simon, Tjoung‐Won , Peterlongo, Paolo , Plaseska-Karanfilska, Dijana, Sawyer, Elinor J. , Schmutzler, Rita K., Shibli, Rana , Soucy, Penny, Tomlinson, Ian , Vachon, Celine M. , Wendt, Camilla, Yang, Xiaohong R. , Easton, Douglas F. , Peterlongo, Paolo , Evans, D Gareth , Chenevix-Trench, Georgia , Sawyer, Elinor J , Dennis, Joe , Tyrer, Jonathan P. , Walker, Logan C. , Michailidou, Kyriaki , Ahearn, Thomas U. , Anton‐Culver, Hoda , Arndt, Volker , Behrens, Sabine , Benı́tez, Javier , Bermisheva, Marina , Bojesen, Stig E. , Brenner, Hermann , Castelao, Jose E. , Clarke, Christine L. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Devilee, Peter , Dörk, Thilo , Dossus, Laure , Eliassen, A. Heather , Eriksson, Mikael , Figueroa, Jonine D. , Fletcher, Olivia , Fritschi, Lin , Gabrielson, Marike , Gago-Domínguez, Manuela , García‐Closas, Montserrat , Giles, Graham G. , González‐Neira, Anna , Guénel, Pascal , Hall, Per N , Hollestelle, Antoinette , Hoppe, Reiner , Hopper, John L. , Howell, Anthony , Jakubowska, Anna , John, Esther M. , Jones, Michael E. , Jung, Audrey , Kaaks, Rudolf , Хуснутдинова, Э. К. , Kitahara, Cari M. , Koutros, Stella , Kraft, Peter , Lambrechts, Diether , Manoukian, Siranoush , Margolin, Sara , Milne, Roger L. , Muranen, Taru , Murphy, Rachel A. , Nevanlinna, Heli , Olson, Janet E. , Olsson, Håkan , Perou, Charles M. , Pylkäs, Katri , Rennert, Gad , Saloustros, Emmanouil , Sandler, Dale P. , Schmidt, Marjanka K. , Smeets, Ann , Southey, Melissa C. , Swerdlow, Anthony J. , Tamimi, Rulla M. , Taylor, Jack A. , Teras, Lauren R. , Terry, Mary Beth , Troester, Melissa A. , Truong, Thérèse , Vachon, Celine M. , Wendt, Camilla, Winqvist, Robert , Wolk, Alicja , Zheng, Wei , Ziogas, Argyrios , Simard, Jacques , Dunning, Alison M. , Pharoah, Paul D.P.
No container title available | June 22, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract BackgroundCopy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data.ResultsGene burden tests detected the strongest association for deletions in BRCA1 (P= 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P= 0.0008), ATM (P= 0.002) and BRCA2 (P= 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci.ConclusionsThis is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
Genome-Wide Interaction Analysis of Menopausal Hormone Therapy Use and Breast Cancer Risk Among 62,370 Women
Wang, Xiaoliang , Auer, Paul L. , Wang, Qin , Bolla, Manjeet K. , Aronson, Kristan J. , Lee, Derrick G. , Mulot, Claire , Patel, Alpa V. , Hoppe, Reiner , Lo, Wing‐Yee, Brüning, Thomas , Hamann, Ute , Larson, Nicole L. , Ruddy, Kathryn J. , Haiman, Christopher A. , Krüger, Ute , Wagner, Philippe , Vachon, Celine M. , Hunter, David J. , Andrulis, Irene L., Linet, Martha S. , Prentice, Ross L. , Easton, Douglas F. , Chang‐Claude, Jenny , Lindström, Sara , Wang, Xiaoliang , Middha, Pooja , Dennis, Joe , Dunning, Alison M. , Lush, Michael J. , Michailidou, Kyriaki , Murphy, Rachel A. , Brooks‐Wilson, Angela , Cordina‐Duverger, Emilie , Guénel, Pascal , Truong, Thérèse , Teras, Lauren R. , Dossus, Laure , Kaaks, Rudolf , Czene, Kamila , Gabrielson, Marike , Hall, Per N , Eriksson, Mikael , Jung, Audrey , Becher, Heiko , Couch, Fergus J. , Olson, Janet E. , Giles, Graham G. , MacInnis, Robert J. , Southey, Melissa C. , Marchand, Loı̈c Le , Wilkens, Lynne R. , Olsson, Håkan , Augustinsson, Annelie , Scott, Christopher G. , Winham, Stacey J. , Vachon, Celine M. , Perou, Charles M. , Olshan, Andrew F. , Troester, Melissa A. , Eliassen, A. Heather , Tamimi, Rulla M. , Brantley, Kristen D. , Figueroa, Jonine D. , Chanock, Stephen Jacob , Ahearn, Thomas U. , García‐Closas, Montserrat , Evans, D. Gareth , Newman, William G. , Veen, Elke M. van , Howell, Anthony , Wolk, Alicja , Håkansson, Niclas , Anton‐Culver, Hoda , Ziogas, Argyrios , Jones, Michael E. , Orr, Nick , Schoemaker, Minouk J. , Swerdlow, Anthony J. , Kitahara, Cari M. , Milne, Roger L. , Kraft, Peter
No container title available | May 24, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values<5x10-8 as genome-wide significant, and p-values<1x10-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values<1x105. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.