Citations 13
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.
Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk
Middha, Pooja , Choudhury, Parichoy Pal , Wilcox, Amber N , Lindström, Sara , Behrens, Sabine , Michailidou, Kyriaki , Bolla, Manjeet K. , Wang, Qin , Jung, Audrey , Abu‐Ful, Zomoroda, Andrulis, Irene L. , Aronson, Kristan J. , Auer, Paul L. , Becher, Heiko , Beckmann, Matthias W. , Beeghly‐Fadiel, Alicia, Bojesen, Stig E. , Brauch, Hiltrud , Brenner, Hermann , Brüning, Thomas , Campa, Daniele , Carracedo, Ãngel , Carter, Brian D., Castelao, Jose E. , Chatterjee, Nilanjan , Chenevix‐Trench, Georgia , Cox, Angela , Earp, H. Shelton , Ekici, Arif B. , Eliassen, A. Heather , Eriksson, Mikael , Evans, D. Gareth , Fasching, Peter A. , Figueroa, Jonine D. , Gabrielson, Marike , Gago-Domínguez, Manuela , Gao, Chi , Gapstur, Susan M. , Gaudet, Mia M. , González‐Neira, Anna , Guénel, Pascal , Haeberle, Lothar, Haiman, Christopher A. , Håkansson, Niclas , Hamann, Ute, Hatse, Sigrid , Holleczek, Bernd , Hoover, Robert N. , Hopper, John L. , Hunter, David J. , Investigators, ABCTB, Investigators, kConFab/AOCS, John, Esther M. , Jones, Michael E. , Kaaks, Rudolf, Keeman, Renske , Ko, Yon-Dschun, Koutros, Stella , Kurian, Allison W. , Lambrechts, Diether , Lee, Eunjung , Lejbkowicz, Flavio, Linet, Martha S. , Lissowska, Jolanta , Llaneza, Ana, MacInnis, Robert J. , Martinez, Maria Elena, Maurer, Tabea, Newman, William G, Orr, Nick , Perou, Charles M. , Pita, Guillermo , Prentice, Ross L. , Rennert, Gad , Rennert, Hedy S., Ruddy, Kathryn J. , Schoemaker, Minouk J. , Scott, Rodney J. , Smeets, Ann , Spinelli, John J. , Stone, Jennifer , Taylor, Jack A. , Vachon, Celine M. , Veen, Elke M. van , Weltens, Caroline , Yang, Xiaohong R. , Easton, Douglas F. , García‐Closas, Montserrat , Chang‐Claude, Jenny, Newman, William G. , Lambrechts, Diether , Norman, Aaron, Polley, Eric C. , Lambrechts, Diether , Rennert, Gad , Behrens, Sabine , Lissowska, Jolanta , Evans, D Gareth , John, Esther M , Maclnnis, Robert , Perou, Charles M , Jones, Michael E , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Gago-Dominguez, Manuela , Guénel, Pascal , Kapoor, Pooja Middha , Koutros, Stella , Newman, William G , García-Closas, Montserrat , Ekici, Arif B , Michailidou, Kyriaki , Taylor, Jack A , Chenevix-Trench, Georgia , Kurian, Allison W , Eriksson, Mikael , Figueroa, Jonine D , Jung, Audrey Y , Becher, Heiko , Eliassen, A Heather , Gabrielson, Marike , Håkansson, Niclas , Stone, Jennifer , Bojesen, Stig E , Schoemaker, Minouk J , Wang, Qin , Brauch, Hiltrud , Orr, Nick , Mavaddat, Nasim , Hurson, Amber N. , Dennis, Joe , Ahearn, Thomas U. , Anton‐Culver, Hoda , Arndt, Volker , Freeman, Laura E. Beane , Beeghly‐Fadiel, Alicia , Benı́tez, Javier , Bernstein, Leslie , Cai, Qiuyin , Canzian, Federico , Chanock, Stephen Jacob , Clarke, Christine L. , Couch, Fergus J. , Cross, Simon S. , Czene, Kamila , Dai, James Y. , Fritschi, Lin , Giles, Graham G. , Hall, Per N , Heyworth, Jane , Howell, Anthony , Investigators, ABCTB, Investigators, kConFab/AOCS, Kitahara, Cari M. , Ko, Yon‐Dschun, Marchand, Loı̈c Le , McLean, Catriona , Neuhausen, Susan L. , Norman, Aaron D. , O’Brien, Katie M. , Olshan, Andrew F. , Olson, Janet E. , Olsson, Håkan , Sandler, Dale P. , Saunders, Christobel , Schöttker, Ben , Schumacher, Fredrick R. , Scott, Christopher G. , Shu, Xiao‐Ou , Southey, Melissa C. , Swerdlow, Anthony J. , Tamimi, Rulla M. , Troester, Melissa A. , Vachon, Celine M. , Wang, Xiaoliang , Weinberg, Clarice R. , Willett, Walter C. , Winham, Stacey J. , Wolk, Alicja , Zheng, Wei , Ziogas, Argyrios , Dunning, Alison M. , Pharoah, Paul D.P. , Schmidt, Marjanka K. , Kraft, Peter , Milne, Roger L.
JNCI: Journal of the National Cancer Institute | April 23, 2020 | Volume: 113 | Issue: 3 | Pages: 329-337
Abstract We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status
Feng, Helian , Gusev, Alexander , Wu, Lang , Abu-Full, Zomoroda, Aittomäki, Kristiina, Andrulis, Irene L. , Antoniou, Antonis C. , Arason, Aðalgeir , Arndt, Volker , Aronson, Kristan J. , Asseryanis, Ella, Auer, Paul L. , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barrowdale, Daniel , Beckmann, Matthias W. , Bermisheva, Marina , Białkowska, Katarzyna , Bogdanova, Natalia , Bojesen, Stig E. , Bolla, Manjeet K. , Borg, Åke , Brauch, Hiltrud , Brenner, Hermann , Brüning, Thomas , Burwinkel, Barbara , Caldés, Trinidad , Canisius, Sander , Campa, Daniele , Carter, Brian D., Castelao, Jose E. , Chang‐Claude, Jenny , Christiansen, Hans , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Cox, Angela , Daly, Mary B., Leeneer, Kim De , Dörk, Thilo , Dwek, Miriam , Eccles, Diana M., Ejlertsen, Bent , Engel, Christoph , Fasching, Peter A. , Flyger, Henrik, Friedman, Eitan , Frost, Debra, Gabrielson, Marike , Ganz, Patricia A. , Gapstur, Susan M. , García‐Closas, Montserrat , Gaudet, Mia M. , Glendon, Gord , Goldberg, Mark S. , Goldgar, David E., González‐Neira, Anna , Greene, Mark H. , Guénel, Pascal , Haiman, Christopher A. , Hamann, Ute, Hake, Christopher R., He, Wei , Heyworth, Jane , Hogervorst, Frans B.L., Hooning, Maartje J. , Hoover, Robert N. , Hopper, John L. , Huang, Guanmengqian, Hulick, Peter J. , Humphreys, Keith , Imyanitov, Evgeny N., Investigators, ABCTB, Investigators, HEBON, Investigators, BCFR, Investigators, OCGN, Jakimovska, Milena , Jakubowska, Anna , James, Paul A. , Janavicius, Ramunas, Jankowitz, Rachel C. , John, Esther M. , Johnson, Nichola , Jung, Audrey , Kiiski, Johanna I. , Konstantopoulou, Irene , Kristensen, Vessela N. , Laitman, Yael , Lambrechts, Diether , Leroux, Dominique, Lester, Jenny, Lesueur, Fabienne , Lindor, Noralane M. , Lindström, Sara, Lo, Wing‐Yee, Loud, Jennifer T. , Makalic, Enes , Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush , Margolin, Sara , Matricardi, Laura , Maurer, Tabea, Mavroudis, Dimitrios, McGuffog, Lesley, Meindl, Alfons , Menon, Usha , Michailidou, Kyriaki , Kapoor, Pooja M., Montagna, Marco , Moreno, Fernando , Muranen, Taru , Nathanson, Katherine L. , Nevelsteen, Ines, Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Olsson, Håkan , Osório, Ana , Papp, J., Park‐Simon, Tjoung‐Won , Pedersen, Inge Søkilde , Peixoto, Ana , Peterlongo, Paolo , Peto, Julian , Phillips, Kelly‐Anne , Plaseska‐Karanfilska, Dijana , Poppe, Bruce , Pradhan, Nisha , Prajzendanc, Karolina , Punie, Kevin , Pylkäs, Katri , Rantala, Johanna, Rashid, Muhammad Usman , Rennert, Gad , Romero, Atocha , Saloustros, Emmanouil , Sandler, Dale P. , Santos, Catarina , Sawyer, Elinor J. , Schmutzler, Rita K., Schoemaker, Minouk J. , Scott, Rodney J. , Simard, Jacques , Skytte, Anne‐Bine , Soucy, Penny, Spinelli, John J. , Stone, Jennifer , Tapper, William , Taylor, Jack A. , Teixeira, Manuel R. , Terry, Mary Beth , Teulé, Àlex , Thomassen, Mads , Thöne, Kathrin , Thull, Darcy L. , Tollenaar, Rob A.�E.�M. , Torres, Diana , Vachon, Celine M. , Ouweland, Ans M.W. van den, Vega, Ana , Viel, Alessandra , Vieiro‐Balo, Paula, Wang, Qin , Wappenschmidt, Barbara , Weinberg, Clarice R. , Weitzel, Jeffrey N. , Wendt, Camilla, Winqvist, Robert , Yang, Xiaohong R., Easton, Douglas F. , Chenevix‐Trench, Georgia , Durocher, Francine , Eccles, Diana , Janavičius, Ramūnas , Khaw, Kay‐Tee , Lambrechts, Diether , Lindor, Noralane, Dörk, Thilo , Lambrechts, Diether , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Rennert, Gad , Sandler, Dale P , Teixeira, Manuel R , Eccles, Diana , Menon, Usha , Vega, Ana , Weitzel, Jeffrey N , Claes, Kathleen B M , Azzollini, Jacopo , John, Esther M , Konstantopoulou, Irene , Matricardi, Laura , Olopade, Olufunmilayo I , Arndt, Volker , Jakubowska, Anna , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , Muranen, Taru A , Romero, Atocha , Saloustros, Emmanouil , Torres, Diana , García-Closas, Montserrat , Makalic, Enes , Michailidou, Kyriaki , Bogdanova, Natalia V , Taylor, Jack A , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Engel, Christoph , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Jung, Audrey Y , Gabrielson, Marike , Stone, Jennifer , Pylkäs, Katri , Rashid, Muhammad U , De Leeneer, Kim , Manoukian, Siranoush , Bojesen, Stig E , Schoemaker, Minouk J , Weinberg, Clarice R , Phillips, Kelly-Anne , Terry, Mary Beth , Brauch, Hiltrud , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Paşaniuc, Bogdan , Long, Jirong , Anton‐Culver, Hoda , Arun, Banu , Balmañà, Judith , Barnes, Daniel R. , Behrens, Sabine , Benı́tez, Javier , Blanco, Ana , Blomqvist, Carl , Boeckx, Bram , Bonanni, Bernardo , Borg, Åke , Briceño, Ignacio , Broeks, Annegien , Cai, Qiuyin , Caligo, Maria A. , Campbell, Ian , Carter, Jonathan , Chanock, Stephen Jacob , Chung, Wendy K. , Clarke, Christine L. , Collaborators, GEMO Study, Collaborators, EMBRACE, Collaborators, GC‐HBOC study, Couch, Fergus J. , Cross, Simon S. , Cybulski, Cezary , Czene, Kamila , Hoya, Miguel de la , Dennis, Joe , Devilee, Peter , Dı́ez, Orland , Domchek, Susan M. , dos‐Santos‐Silva, Isabel , Dunning, Alison M. , Ellberg, Carolina , Eriksson, Mikael , Fletcher, Olivia , Fostira, Florentia , Fritschi, Lin , Garber, Judy E. , García-Sáenz, José Á. , Giles, Graham G. , Godwin, Andrew K. , Goldgar, David E., Gronwald, Jacek , Hall, Per N , Hollestelle, Antoinette , Investigators, ABCTB, Investigators, HEBON, Investigators, BCFR, Investigators, OCGN, Isaacs, Claudine , Vijai, Joseph , Karlan, Beth Y. , Хуснутдинова, Э. К. , Lázaro, Conxi , Leslie, Goska , Lubiński, Jan , Mannermaa, Arto, Martens, John W.M. , Martı́nez, Marı́a Elena , Meindl, Alfons , Kapoor, Pooja M., Miller, Austin , Moserle, Lidia , Mulligan, Anna Marie , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Parsons, Michael T. , Pharoah, Paul D.P. , Presneau, Nadège , Radice, Paolo , Risch, Harvey A. , Robson, Mark E. , Schmidt, Marjanka K. , Schmidt, Daniel F. , Sharma, Priyanka , Shu, Xiao‐Ou , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Swerdlow, Anthony J. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Truong, Thérèse , Tung, Nadine , Vachon, Celine M. , Asperen, Christi J. van , Rensburg, Elizabeth J. van , Yannoukakos, Drakoulis , Ziogas, Argyrios , Milne, Roger L. , Zheng, Wei , Kraft, Peter , Jiang, Xia
Genetic Epidemiology | March 2, 2020 | Volume: 44 | Issue: 5 | Pages: 442-468
AbstractPrevious transcriptome‐wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome‐wide association studies (GWAS), but analyses of breast cancer subtype‐specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta‐analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case‐only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS‐significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast‐cancer gene in three of six regions harboring multiple TWAS‐significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer.