| Literature DB >> 33022221 |
Iris Kramer1, Maartje J Hooning2, Nasim Mavaddat3, Michael Hauptmann4, Renske Keeman1, Ewout W Steyerberg5, Daniele Giardiello6, Antonis C Antoniou3, Paul D P Pharoah7, Sander Canisius8, Zumuruda Abu-Ful9, Irene L Andrulis10, Hoda Anton-Culver11, Kristan J Aronson12, Annelie Augustinsson13, Heiko Becher14, Matthias W Beckmann15, Sabine Behrens16, Javier Benitez17, Marina Bermisheva18, Natalia V Bogdanova19, Stig E Bojesen20, Manjeet K Bolla3, Bernardo Bonanni21, Hiltrud Brauch22, Michael Bremer23, Sara Y Brucker24, Barbara Burwinkel25, Jose E Castelao26, Tsun L Chan27, Jenny Chang-Claude28, Stephen J Chanock29, Georgia Chenevix-Trench30, Ji-Yeob Choi31, Christine L Clarke32, J Margriet Collée33, Fergus J Couch34, Angela Cox35, Simon S Cross36, Kamila Czene37, Mary B Daly38, Peter Devilee39, Thilo Dörk40, Isabel Dos-Santos-Silva41, Alison M Dunning42, Miriam Dwek43, Diana M Eccles44, D Gareth Evans45, Peter A Fasching46, Henrik Flyger47, Manuela Gago-Dominguez48, Montserrat García-Closas29, José A García-Sáenz49, Graham G Giles50, David E Goldgar51, Anna González-Neira52, Christopher A Haiman53, Niclas Håkansson54, Ute Hamann55, Mikael Hartman56, Bernadette A M Heemskerk-Gerritsen2, Antoinette Hollestelle2, John L Hopper57, Ming-Feng Hou58, Anthony Howell59, Hidemi Ito60, Milena Jakimovska61, Anna Jakubowska62, Wolfgang Janni63, Esther M John64, Audrey Jung16, Daehee Kang65, C Marleen Kets66, Elza Khusnutdinova67, Yon-Dschun Ko68, Vessela N Kristensen69, Allison W Kurian70, Ava Kwong71, Diether Lambrechts72, Loic Le Marchand73, Jingmei Li74, Annika Lindblom75, Jan Lubiński76, Arto Mannermaa77, Mehdi Manoochehri55, Sara Margolin78, Keitaro Matsuo60, Dimitrios Mavroudis79, Alfons Meindl80, Roger L Milne50, Anna Marie Mulligan81, Taru A Muranen82, Susan L Neuhausen83, Heli Nevanlinna82, William G Newman45, Andrew F Olshan84, Janet E Olson85, Håkan Olsson13, Tjoung-Won Park-Simon40, Julian Peto41, Christos Petridis86, Dijana Plaseska-Karanfilska61, Nadege Presneau43, Katri Pylkäs87, Paolo Radice88, Gad Rennert9, Atocha Romero89, Rebecca Roylance90, Emmanouil Saloustros91, Elinor J Sawyer92, Rita K Schmutzler93, Lukas Schwentner63, Christopher Scott85, Mee-Hoong See94, Mitul Shah42, Chen-Yang Shen95, Xiao-Ou Shu96, Sabine Siesling97, Susan Slager85, Christof Sohn98, Melissa C Southey99, John J Spinelli100, Jennifer Stone101, William J Tapper44, Maria Tengström102, Soo Hwang Teo103, Mary Beth Terry104, Rob A E M Tollenaar105, Ian Tomlinson106, Melissa A Troester84, Celine M Vachon107, Chantal van Ongeval108, Elke M van Veen45, Robert Winqvist87, Alicja Wolk109, Wei Zheng96, Argyrios Ziogas11, Douglas F Easton7, Per Hall110, Marjanka K Schmidt111.
Abstract
Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.Entities:
Keywords: contralateral breast cancer; epidemiology; genetic; polygenic risk score
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Year: 2020 PMID： 33022221 PMCID： PMC7675034 DOI： 10.1016/j.ajhg.2020.09.001
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025