Citations 4
Genome-wide Interaction Analysis of Menopausal Hormone Therapy Use and Breast Cancer Risk among 62,370 Women
Kapoor, Pooja, Auer, Paul, Dennis, Joe, Wang, Qin , Bolla, Manjeet K. , Aronson, Kristan J. , Lee, Derrick , Cordina‐Duverger, Emilie, Mulot, Claire , Teras, Lauren R., Patel, Alpa V. , Hoppe, Reiner , Lo, Wing‐Yee, Brüning, Thomas , Hamann, Ute, Couch, Fergus, Ruddy, Kathryn J. , MacInnis, Robert J. , Wilkens, Lynne, Haiman, Christopher A. , Krüger, Ute , Wagner, Philippe , Vachon, Celine M. , Eliassen, Heather, Andrulis, Irene L. , Evans, D. Gareth , Ziogas, Argyrios, Orr, Nick , Linet, Martha S. , Prentice, Ross L. , Easton, Douglas F. , Chang‐Claude, Jenny , Lindström, Sara , Evans, D Gareth , Maclnnis, Robert , Orr, Nick , Wang, Xiaoliang , Kapoor, Pooja, Dunning, Alison M. , Lush, Michael J. , Michailidou, Kyriaki , Murphy, Rachel A. , Brooks‐Wilson, Angela , 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. , Larson, Nicole, Olson, Janet E. , Giles, Graham G. , Southey, Melissa C. , Marchand, Loı̈c Le , Wilkens, Lynne R. , Olsson, Håkan , Augustinsson, Annelie , Scott, Christopher, Winham, Stacey J. , Vachon, Celine M. , Perou, Charles M. , Olshan, Andrew F. , Troester, Melissa A. , Hunter, David, Eliassen, A. Heather , Tamimi, Rulla M. , Brantley, Kristen D. , Figueroa, Jonine D. , Chanock, Stephen Jacob , Ahearn, Thomas U. , García‐Closas, Montserrat , Newman, William G. , Veen, Elke M. van , Howell, Anthony , Wolk, Alicja , Håkansson, Niclas , Anton‐Culver, Hoda , Jones, Michael E. , Schoemaker, Minouk J. , Swerdlow, Anthony J. , Kitahara, Cari M. , Milne, Roger L. , Kraft, Peter
No container title available | July 2, 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.
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.
Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk
Lin, Wei‐Yu , Camp, Nicola J. , Ghoussaini, Maya , Beesley, Jonathan, Michailidou, Kyriaki , Hopper, John L. , Apicella, Carmel, Southey, Melissa C. , Stone, Jennifer , Schmidt, Marjanka K. , Veer, Laura J. van’t , Muir, Kenneth , Lophatananon, Artitaya, Stewart‐Brown, Sarah , Siriwanarangsan, Pornthep, Fasching, Peter A. , Haeberle, Lothar, Ekici, Arif B. , Beckmann, Matthias W. , Peto, Julian, dos‐Santos‐Silva, Isabel , Fletcher, Olivia , Johnson, Nichola , Bolla, Manjeet K. , Wang, Qin, Sawyer, Elinor J. , Cheng, Timothy, Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Surowy, Harald , Burwinkel, Barbara , Guénel, Pascal , Truong, Thérèse , Ménégaux, F. , Mulot, Claire , Bojesen, Stig E. , Nordestgaard, Børge G. , Nielsen, Sune F. , Flyger, Henrik, Benı́tez, Javier , Zamora, M. Pilar , Pérez, José Ignacio Arias , Menéndez, Primitiva, González‐Neira, Anna , Pita, Guillermo , Alonso, M. Rosario, Álvarez, Núria, Herrero, Daniel, Brenner, Hermann , Dieffenbach, Aida Karina, Stegmaier, Christa, Meindl, Alfons , Lichtner, Peter , Schmutzler, Rita K., Müller‐Myhsok, Bertram , Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Network, The GENICA, Tessier, Daniel C., Vincent, Daniel , Bacot, François, Nevanlinna, Heli , Aittomäki, Kristiina, Blomqvist, Carl , Khan, Sofia , Matsuo, Keitaro , Iwata, Hiroji, Horio, Akiyo, Bogdanova, Natalia , Antonenkova, Natalia, Dörk, Thilo , Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti, Hartikainen, Jaana M. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wu, Anna H. , Tseng, Chiu-Chen , Neven, Patrick , Wauters, Els , Wildiers, Hans , Lambrechts, Diether , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Couch, Fergus J. , Vachon, Celine M. , Purrington, Kristen S. , Giles, Graham G. , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Simard, Jacques , Goldberg, Mark S. , Dumont, Martine , Teo, Soo‐Hwang , Yip, Cheng Har , Vithana, Eranga N. , Kristensen, Vessela N. , Deming-Halverson, Sandra, Shrubsole, Martha J. , Long, Jirong , Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Kauppila, Saila , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Tchatchou, Sandrine, Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, García‐Closas, Montserrat , Figueroa, Jonine D. , Lissowska, Jolanta , Brinton, Louise A. , Czene, Kamila , Darabi, Hatef, Eriksson, Mikael , Brand, Judith S. , Hooning, Maartje J. , Hollestelle, Antoinette , Ouweland, Ans M.W. van den, Jager, Agnes , Li, Jingmei , Liu, Jianjun , Humphreys, Keith , Shu, Xiao‐Ou , Lu, Wei , Gao, Yu‐Tang , Cai, Hui , Cross, Simon S. , Reed, Malcolm , Blot, William J. , Signorello, Lisa B., Cai, Qiuyin, Perkins, Barbara, Shah, Mitul, Blows, Fiona M., Kang, Daehee , Yoo, Keun-Young, Noh, Dong‐Young , Hartman, Mikael , Miao, Hui , Chia, Kee Seng , Putti, Thomas Choudary , Hamann, Ute , Luccarini, Craig , Baynes, Caroline, Maranian, Mel, Healey, Catherine S., Jakubowska, Anna , Lubiński, Jan , Jaworska–Bieniek, Katarzyna, Durda, Katarzyna, Sangrajrang, Suleeporn , Gaborieau, Valérie , Brennan, Paul , McKay, James , Slager, Susan, Yannoukakos, Drakoulis , Hsiung, Chia‐Ni , Wu, Pei‐Ei , Ding, Shian-ling, Ashworth, Alan , Jones, Michael E. , Orr, Nick , Swerdlow, Anthony J. , Makalic, Enes , Bui, Minh , Hunter, David J. , Hein, Rebecca, Dahmen, Norbert, Beckmann, Lars , Aaltonen, Kirsimari, Muranen, Taru , Heikkinen, Tuomas , Irwanto, Astrid , Rahman, Nazneen , Turnbull, Clare , Study, The Breast and Ovarian Cancer Susceptibility (BOCS), Waisfisz, Quinten , Meijers‐Heijboer, Hanne , Adank, Muriel A. , Luijt, Rob B. van der , Chenevix‐Trench, Georgia , Dunning, Alison M. , Easton, Douglas F. , Cox, Angela , Durocher, Francine , Zheng, Wei , Thorne, Heather , Lambrechts, Diether , Vachon, Celine, Broeks, Annegien , Rutgers, Emiel J. , Wang, Qin, Dennis, Joe , Marmé, Frederik , Anton‐Culver, Hoda , Arndt, Volker , Meindl, Alfons , Network, The GENICA, Ito, Hidemi , Iwata, Hiroji , Mannermaa, Arto , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Berg, David Van Den , Stram, Daniel O. , Rudolph, Anja , Seibold, Petra , Bonanni, Bernardo , Couch, Fergus J. , Wang, Xianshu , Vachon, Celine M. , Milne, Roger L. , Marchand, Loı̈c Le , Labrèche, France , Rudolph, Anja , Zheng, Wei , Asperen, Christi J. van , Eriksson, Mikael , Hooning, Maartje J. , Pharoah, Paul D.P. , Ahmed, Shahana , Toland, Amanda Ewart , Shen, Chen‐Yang , Tsimiklis, Helen , Schmidt, Daniel Frederick , Bui, Minh , Chanock, Stephen Jacob , Study, The Breast and Ovarian Cancer Susceptibility (BOCS), Hall, Per N , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Teo, Soo H , Shrubsole, Martha J , Swerdlow, Anthony J , Radice, Paolo , Lissowska, Jolanta , Southey, Melissa C , van der Luijt, Rob B , Muir, Kenneth , Shu, Xiao-Ou , Matsuo, Keitaro , Dunning, Alison M , Jakubowska, Anna , Jones, Michael E , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , Hartman, Mikael , Li, Jingmei , Muranen, Taru A , García-Closas, Montserrat , Schmidt, Marjanka K , Makalic, Enes , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Czene, Kamila , Stone, Jennifer , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Purrington, Kristen S , Truong, Therese , Wildiers, Hans , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , Liu, Jing , Kang, Daehee
Human Molecular Genetics | August 29, 2014 | Volume: 24 | Issue: 1 | Pages: 285-298
A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46 450 cases and 42 461 controls from the breast cancer association consortium
Herránz, Jesús , Michailidou, Kyriaki , Zamora, M. Pilar , Pérez, José Ignacio Arias , González‐Neira, Anna , Pita, Guillermo , Alonso, M. Rosario, Wang, Qin , Bolla, Manjeet K. , Czene, Kamila , Eriksson, Mikael , Humphreys, Keith , Darabi, Hatef, Li, Jingmei , Hopper, John L. , Apicella, Carmel, Southey, Melissa C. , Chenevix‐Trench, Georgia , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nicholas, Schoemaker, Minouk J. , Jakubowska, Anna , Lubiński, Jan , Jaworska–Bieniek, Katarzyna, Durda, Katarzyna, Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Bojesen, Stig E. , Nordestgaard, Børge G. , Flyger, Henrik, Nevanlinna, Heli , Muranen, Taru , Aittomäki, Kristiina, Blomqvist, Carl , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Vachon, Celine M. , Purrington, Kristen S. , Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Grip, Mervi, Dunning, Alison M. , Shah, Mitul , Guénel, Pascal , Truong, Thérèse , Sanchez, Marie, Mulot, Claire , Brenner, Hermann , Dieffenbach, Aida Karina, Stegmaier, Christa, Lindblom, Annika , Margolin, Sara , Hooning, Maartje J. , Hollestelle, Antoinette , Collée, J. Margriet, Jager, Agnes , Cox, Angela , Brock, Ian W., Reed, Malcolm , Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Simard, Jacques , Dumont, Martine , Soucy, Penny, Dörk, Thilo , Bogdanova, Natalia , Hamann, Ute , Rüdiger, Thomas , Ulmer, Hans-Ulrich, Fasching, Peter A. , Häberle, Lothar , Ekici, Arif B. , Beckmann, Matthias W. , Fletcher, Olivia , Johnson, Nichola , dos‐Santos‐Silva, Isabel , Peto, Julian, Radice, Paolo , Peterlongo, Paolo , Peissel, Bernard , Mariani, P., Severi, Gianluca , Baglietto, Laura , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Marmé, F., Burwinkel, Barbara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Lambrechts, Diether , Yesilyurt, Betül T., Floris, Giuseppe , Leunen, Karin, Alnæs, Grethe Grenaker, Kristensen, Vessela N. , Børresen‐Dale, Anne‐Lise , García‐Closas, Montserrat , Lissowska, Jolanta , Figueroa, Jonine D. , Schmidt, Marjanka K. , Verhoef, Senno, Rutgers, Emiel J. , Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Network, The GENICA, TNBCC, The, Yannoukakos, Drakoulis , Malats, Núria , Easton, Douglas F. , Manoukian, Siranoush , Durocher, Francine , Zaffaroni, Daniela , Orr, Nick , Thorne, Heather , Bowtell, David D.L. , Rabstein, Sylvia , Lotz, Anne , Lambrechts, Diether , Milne, Roger L. , Dennis, Joe , Tyrer, Jonathan P. , Eriksson, Mikael , Anton‐Culver, Hoda , Neuhausen, Susan L. , Ziogas, Argyrios , Clarke, Christina A. , Dite, Gillian S. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Orr, Nicholas, Rudolph, Anja , Seibold, Petra , Wang, Xianshu , Olson, Janet E. , Vachon, Celine M. , Sanchez, Marie, Arndt, Volker , Hooning, Maartje J. , Marchand, Loı̈c Le , Försti, Asta , Giles, Graham G. , Mannermaa, Arto, Chanock, Stephen Jacob , Broeks, Annegien , Network, The GENICA, Couch, Fergus J. , Toland, Amanda Ewart , TNBCC, The, Pharoah, Paul D.P. , Hall, Per N , Benı́tez, Javier , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Peterlongo, Paolo , Swerdlow, Anthony J , Radice, Paolo , Lissowska, Jolanta , Southey, Melissa C , Malats, Nuria , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , Li, Jingmei , Muranen, Taru A , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Simard, Jacques , Chenevix-Trench, Georgia , Figueroa, Jonine D , Czene, Kamila , Bowtell, David D , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Baglietto, Laura , Fletcher, Olivia , Bojesen, Stig E , Purrington, Kristen S , Schoemaker, Minouk J , Truong, Therese , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Human Molecular Genetics | November 16, 2013 | Volume: 23 | Issue: 7 | Pages: 1934-1946
Abstract Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10−4) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10−8. Results from the second analytic approach were consistent with those from the first (P > 10−10). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.