Citations 2
Clarifying risk-factor associations with quantitative breast tumor features: a pooled analysis of 24 studies
Adams, Daniel , Hurson, Amber N. , Ahearn, Thomas U, Andrulis, Irene L, Antoniou, Antonis C, Auvinen, Päivi, Bane, Anita, González, Amy Berrington de , Bodelon, Clara, Bolla, Manjeet K. , Borrero, Maria , Brenner, Hermann, Brock, Ian W., Camp, Nicola J. , Cessna, Melissa H., Chanock, Stephen J, Chenevix-Trench, G, Copson, ER, Fh, Couch, Devilee, P, Easton, Douglas F, Eccles, Diana, Figueroa, Jonine D, Glendon, Gord, Hamann, U, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette A M, Hodge, James M, Holleczek, Bernd, Hollestelle, A M, Mj, Hooning, Investigators, kConFab, Amor, David, Andrews, Lesley , Antill, Y , Rl, Balleine, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Caldon, Liz, Campbell, Ian, Chakrabarti, Anannya , Chauhan, Deepa, Chauhan, Manisha, Christian, Alice, Cohen, Paul, Colley, Alison, Cui, James, Courtney, Eliza, Cummings, Margaret, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Duijf, Pascal, Edwards, Stacey, Farshid, Gelareh , Fellows, AM, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet , Friedlander, Michael, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Harraka, Philip, Hayward, Nick, Hoskins, Cass , Hunt, Clare, James, Paul, Jenkins, Mark, Kidd, Alexa, Koehler, Jessica, Kollias, J, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason , Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Reed, Amy McCart, Milne, Roger, Nightingale, Sophie , O’Connell, Shona, O’Sullivan, Sarah, Reilly, Robert O', Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Ragunathan, Abi, Robinson, Bridget, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta , Simpson, Peter, Mc, Southey, Spurdle, Amanda, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, A H, Tucker, Kathy , Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, I, Young, Mary Ann, Zaheed, Milita , Investigators, S On Behalf Of The Chlovis Study, Tan, Veronique Kiak Mien , Lim, Geok Hoon, Tan, Ern Yu , Tan, Su-Ming, Iau, Philip Tsau Choong , Jakubowska, A, Jones, Michael E. , Jones, Louise , Jones, Brandt, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske , Lawrence, Scott, Li, J M, Lubiński, J, Mannermaa, Arto, Manoochehri, Mehdi, Martens, John W M, Mesker, Wilma E, Muhammad, Noor , Obi, Nadia, Olson, Janet E, Patel, Alpa V, Prajzendanc, Karolina , Ruddy, Kathryn J, Safizadeh, Fatemeh , Schöttker, Ben, Tengström, Maria , Le, Teras, Timmermans, M, Tollenaar, RA, Vachon, Celine M, Wang, Q, Yang, Xiaohong R, Zamora, M Pilar, Chang-Claude, Jenny, Schmidt, M K, Pharoah, Paul D P, Abubakar, Mustapha, Eccles, Diana , Ahearn, Thomas U. , Eccles, Diana , Jones, Michael E , Jones, J. Louise , Berrington de Gonzalez, Amy , Antoniou, Antonis C. , Bane, Anita, Behrens, Sabine , Białkowska, Katarzyna , Bodelón, Clara , Brenner, Hermann , Broeks, Annegien , Chanock, Stephen Jacob , Chenevix‐Trench, Georgia , Copson, Ellen , Couch, Fergus J, Cox, Angela , Cross, Simon S. , Devilee, Peter , Dunning, Alison M. , Easton, Douglas F. , Figueroa, Jonine D. , Glendon, Gord, González‐Neira, Anna , Hartikainen, Jaana M. , Hartman, Mikael , Heemskerk‐Gerritsen, Bernadette A. M. , Ho, Peh Joo , Hodge, James M. , Holleczek, Bernd , Hollestelle, Antoinette , Hooning, Maartje J. , Investigators, kConFab, Balleine, Rosemary L. , Bennett, Ian, Bogwitz, Michael R. , Bodek, Simon , Botes, Leon P., Buckley, Michael , Cohen, Paul A. , Crook, Ashley , Courtney, Eliza , Dawson, Sarah‐Jane , DeFazio, Anna , Delatycki, Martin B. , Duijf, Pascal H. G. , Fellows, Andrew, Fenton, Georgina L. , Flanagan, James M. , Forrest, Laura Elenor , Friedländer, Michael , Harraka, Philip A. , Kidd, Alexa, Kollias, James, Lakhani, Sunil R. , Lawrence, Mitchell, Lindeman, Geoffrey J. , Lippey, Jocelyn , Loi, Sherene , Reed, Amy E. McCart , Milne, Roger L , Gallego‐Ortega, David , Pathak, Gargi, Pearn, Amy , Robinson, Bridget A. , Skandarajah, Anita Rohini , Salisbury, Elizabeth, Saunders, Christobel , Saunus, Jodi M. , Savas, Peter Stephen , Sexton, Adrienne , Shelling, Andrew Neil , Simpson, Peter, Spurdle, Amanda B. , Visvader, Jane E. , Williams, Rachael, Tan, Bien‐Keem , Lim, Geok Hoon , Kaaks, Rudolf , Lawrence, Scott M. , Lissowska, Jolanta , Mannermaa, Arto , Manoochehri, Mehdi, Mesker, Wilma E. , Mulligan, Anna Marie , Obi, Nadia , Olson, Janet E. , Osório, Ana , Ottewell, Penelope Dawn , Patel, Alpa V , Pita, Guillermo , Rashid, Muhammad Usman , Ruddy, Kathryn J. , Schöttker, Ben , Seibold, Petra , Tapper, William , Teras, Lauren R , Timmermans, Mieke, Vachon, Celine M. , Wesseling, Jelle , Yadav, Siddhartha , Chang‐Claude, Jenny , Schmidt, Marjanka K. , Abubakar, Mustapha , García‐Closas, Montserrat
JNCI: Journal of the National Cancer Institute | July 18, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.
PRANA: A Deep Learning Method for Adapting Polygenic Risk Scores to Diverse Ethnic Groups
Levi, Hagai, Wang, Qin, Bolla, Manjeet K. , Dennis, Joe, Andrulis, Irene L., Antonenkova, Natalia, Au, Chun Hang, Freeman, Laura E. Beane, Bermisheva, Marina, Bodelon, Clara, Bojesen, Stig E., Brenner, Hermann, Brock, Ian W., Brüning, Thomas, Byers, Helen, Camp, Nicola J., Castelao, Jose E., Choi, Ji-Yeob, Chung, Wendy K., Collaborators, NBCS, Colonna, Sarah, Couch, Fergus J., Daly, Mary B., Devilee, Peter, Dörk, Thilo, Eliassen, A. Heather, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Faw, Kierstin, García-Closas, Montserrat, Haiman, Christopher A., Hamann, Ute, Hartman, Mikael, Hooning, Maartje J., Hoppe, Reiner , Howell, Sacha J., Investigators, ABCTB, Investigators, SGBCC, Ito, Hidemi, Iwasaki, Motoki, Jakubowska, Anna, Jernström, Helena, Joseph, Vijai, Kaaks, Rudolf, Kang, Daehee, Khusnutdinova, Elza K., Kiprijanovska, Sanja , Koutros, Stella, Kristensen, Vessela N., Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Nicole L. , Marchand, Loic Le, Li, Shuai, Li, Jingmei, Lophatananon, Artitaya, Mannermaa, Arto, Matsuo, Keitaro, Maxwell, Whitney, Muir, Kenneth, Nevelsteen, Ines, Obi, Nadia, O’Brien, Katie M., Ofit, Kenneth, Ottewell, Penelope D., Patel, Alpa V., Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina , Ramachandran, Dhanya, Rashid, Muhammad U., Saloustros, Emmanouil, Sandler, Dale P., Schöttker, Ben, Simard, Jacques, Southey, Melissa C., Stone, Jennifer, Teras, Lauren R., Truong, Thérèse, Weinberg, Clarice R., Yamaji, Taiki , Zheng, Wei, Easton, Douglas F., Elkon, Ran , Lambrechts, Diether , Lambrechts, Diether , Kurian, Allison W. , Li, Shuai , Lambrechts, Diether , Lambrechts, Diether , Kurian, Allison W , Li, Shuai , Levi, Hagai , Au, Chun , Augustinsson, Annelie , Freeman, Laura E. Beane , Behrens, Sabine , Bermisheva, Marina , Bodelón, Clara , Bogdanova, Natalia , Brenner, Hermann , Brock, Ian W., Brüning, Thomas , Byers, Helen, Camp, Nicola J. , Castelao, Jose E. , Choi, Ji-Yeob , Chung, Wendy K. , Colonna, Sarah V. , Couch, Fergus J. , Czene, Kamila , Daly, Mary B., Devilee, Peter , Dörk, Thilo, Evans, D. Gareth , Fasching, Peter A., Faw, Kierstin, Gago-Domínguez, Manuela , García‐Closas, Montserrat , Haiman, Christopher A. , Hartman, Mikael , Ho, Vikki , Ho, Peh Joo , Hooning, Maartje J. , Investigators, S On Behalf Of The Chlovis Study, Iwasaki, Motoki , Jakubowska, Anna, Jernström, Helena , Joseph, Vijai, Kaaks, Rudolf , Хуснутдинова, Э. К. , Koutros, Stella , Kristensen, Vessela N., Kwong, Ava , Marchand, Loı̈c Le , Li, Jingmei, Lophatananon, Artitaya , Mannermaa, Arto , Nevelsteen, Ines , Obi, Nadia , O’Brien, Katie M. , Ottewell, Penelope Dawn , Peterlongo, Paolo , Plaseska‐Karanfilska, Dijana , Radice, Paolo , Ramachandran, Dhanya , Romero, Atocha , Saloustros, Emmanouil , Sandler, Dale P. , Schöttker, Ben , Simard, Jacques , Southey, Melissa C. , Sugier, Pierre‐Emmanuel , Taylor, Jack A. , Teras, Lauren R. , Truong, Thérèse , Weinberg, Clarice R. , Yadav, Siddhartha , Dunning, Alison M. , Mavaddat, Nasim , Easton, Douglas F. , Michailidou, Kyriaki , Shamir, Ron
No container title available | July 15, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Polygenic risk scores (PRSs), which quantify inherited susceptibility to complex traits and diseases, have emerged as valuable tools for risk stratification and precision medicine. Despite their promise, PRS developed on European cohorts often demonstrate substantially reduced predictive accuracy in non-European populations, due to differences in genetic architecture. The disproportionate representation of European ancestry cohorts in genome-wide association studies (GWAS) leads to inequitable deployment of PRS technologies across diverse populations. Here, we introduce PRANA (Polygenic Risk Adaptation via Neural-network Architecture), a deep learning framework that adapts an existing PRS developed on one population to other ancestries. Unlike methods that require large-scale GWAS in the target population, PRANA leverages pre-trained PRS models derived from European cohorts and adapts them using modestly sized cohorts from the target population. We evaluated PRANA on seven complex traits in South Asian, East Asian and Ashkenazi Jewish populations, as well as in selected smaller East Asian subpopulations where the scarcity of training data poses a particular challenge. PRANA mostly improved predictive performance of the baseline PRS models by 5%-20% in terms of effect size (β) and Nagelkerke’s R², and, in most cases, outperformed existing cross-ancestry multi-PRS approaches. These results highlight PRANA as a scalable and practical strategy to reduce disparities in genomic risk prediction and advance the equitable application of PRS in diverse populations.