American Journal of Human Genetics ( IF 8.1 ) Pub Date : 2020-10-05 , DOI: 10.1016/j.ajhg.2020.09.001 Iris Kramer , Maartje J. Hooning , Nasim Mavaddat , Michael Hauptmann , Renske Keeman , Ewout W. Steyerberg , Daniele Giardiello , Antonis C. Antoniou , Paul D.P. Pharoah , Sander Canisius , Zumuruda Abu-Ful , Irene L. Andrulis , Hoda Anton-Culver , Kristan J. Aronson , Annelie Augustinsson , Heiko Becher , Matthias W. Beckmann , Sabine Behrens , Javier Benitez , Marina Bermisheva , Natalia V. Bogdanova , Stig E. Bojesen , Manjeet K. Bolla , Bernardo Bonanni , Hiltrud Brauch , Michael Bremer , Sara Y. Brucker , Barbara Burwinkel , Jose E. Castelao , Tsun L. Chan , Jenny Chang-Claude , Stephen J. Chanock , Georgia Chenevix-Trench , Ji-Yeob Choi , Christine L. Clarke , J. Margriet Collée , Fergus J. Couch , Angela Cox , Simon S. Cross , Kamila Czene , Mary B. Daly , Peter Devilee , Thilo Dörk , Isabel dos-Santos-Silva , Alison M. Dunning , Miriam Dwek , Diana M. Eccles , D. Gareth Evans , Peter A. Fasching , Henrik Flyger , Manuela Gago-Dominguez , Montserrat García-Closas , José A. García-Sáenz , Graham G. Giles , David E. Goldgar , Anna González-Neira , Christopher A. Haiman , Niclas Håkansson , Ute Hamann , Mikael Hartman , Bernadette A.M. Heemskerk-Gerritsen , Antoinette Hollestelle , John L. Hopper , Ming-Feng Hou , Anthony Howell , Hidemi Ito , Milena Jakimovska , Anna Jakubowska , Wolfgang Janni , Esther M. John , Audrey Jung , Daehee Kang , C. Marleen Kets , Elza Khusnutdinova , Yon-Dschun Ko , Vessela N. Kristensen , Allison W. Kurian , Ava Kwong , Diether Lambrechts , Loic Le Marchand , Jingmei Li , Annika Lindblom , Jan Lubiński , Arto Mannermaa , Mehdi Manoochehri , Sara Margolin , Keitaro Matsuo , Dimitrios Mavroudis , Alfons Meindl , Roger L. Milne , Anna Marie Mulligan , Taru A. Muranen , Susan L. Neuhausen , Heli Nevanlinna , William G. Newman , Andrew F. Olshan , Janet E. Olson , Håkan Olsson , Tjoung-Won Park-Simon , Julian Peto , Christos Petridis , Dijana Plaseska-Karanfilska , Nadege Presneau , Katri Pylkäs , Paolo Radice , Gad Rennert , Atocha Romero , Rebecca Roylance , Emmanouil Saloustros , Elinor J. Sawyer , Rita K. Schmutzler , Lukas Schwentner , Christopher Scott , Mee-Hoong See , Mitul Shah , Chen-Yang Shen , Xiao-Ou Shu , Sabine Siesling , Susan Slager , Christof Sohn , Melissa C. Southey , John J. Spinelli , Jennifer Stone , William J. Tapper , Maria Tengström , Soo Hwang Teo , Mary Beth Terry , Rob A.E.M. Tollenaar , Ian Tomlinson , Melissa A. Troester , Celine M. Vachon , Chantal van Ongeval , Elke M. van Veen , Robert Winqvist , Alicja Wolk , Wei Zheng , Argyrios Ziogas , Douglas F. Easton , Per Hall , Marjanka K. Schmidt , Anne-Lise Børresen-Dale , Kristine Sahlberg , Lars Ottestad , Rolf Kåresen , Ellen Schlichting , Marit Muri Holmen , Toril Sauer , Vilde Haakensen , Olav Engebråten , Bjørn Naume , Alexander Fosså , Cecile Kiserud , Kristin Reinertsen , Åslaug Helland , Margit Riis , Jürgen Geisler , Grethe Grenaker Alnæs , Christine Clarke , Deborah Marsh , Rodney Scott , Robert Baxter , Desmond Yip , Jane Carpenter , Alison Davis , Nirmala Pathmanathan , Peter Simpson , J. Dinny Graham , Mythily Sachchithananthan , David Amor , Lesley Andrews , Yoland Antill , Rosemary Balleine , Jonathan Beesley , Ian Bennett , Michael Bogwitz , Leon Botes , Meagan Brennan , Melissa Brown , Michael Buckley , Jo Burke , Phyllis Butow , Liz Caldon , Ian Campbell , Deepa Chauhan , Manisha Chauhan , Georgia Chenevix-Trench , Alice Christian , Paul Cohen , Alison Colley , Ashley Crook , James Cui , Margaret Cummings , Sarah-Jane Dawson , Anna deFazio , Martin Delatycki , Rebecca Dickson , Joanne Dixon , Ted Edkins , Stacey Edwards , Gelareh Farshid , Andrew Fellows , Georgina Fenton , Michael Field , James Flanagan , Peter Fong , Laura Forrest , Stephen Fox , Juliet French , Michael Friedlander , Clara Gaff , Mike Gattas , Peter George , Sian Greening , Marion Harris , Stewart Hart , Nick Hayward , John Hopper , Cass Hoskins , Clare Hunt , Paul James , Mark Jenkins , Alexa Kidd , Judy Kirk , Jessica Koehler , James Kollias , Sunil Lakhani , Mitchell Lawrence , Geoff Lindeman , Lara Lipton , Liz Lobb , Graham Mann , Deborah Marsh , Sue Anne McLachlan , Bettina Meiser , Roger Milne , Sophie Nightingale , Shona O'Connell , Sarah O'Sullivan , David Gallego Ortega , Nick Pachter , Briony Patterson , Amy Pearn , Kelly Phillips , Ellen Pieper , Edwina Rickard , Bridget Robinson , Mona Saleh , Elizabeth Salisbury , Christobel Saunders , Jodi Saunus , Rodney Scott , Clare Scott , Adrienne Sexton , Andrew Shelling , Peter Simpson , Melissa Southey , Amanda Spurdle , Jessica Taylor , Renea Taylor , Heather Thorne , Alison Trainer , Kathy Tucker , Jane Visvader , Logan Walker , Rachael Williams , Ingrid Winship , Mary Ann Young
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.
中文翻译：
乳腺癌多基因风险评分和对侧乳腺癌风险
先前的研究表明，多基因风险评分（PRS）可用于根据女性患原发性浸润性乳腺癌的风险对她们进行分层。本研究旨在评估最近验证的 313 种系变异 (PRS 313 ) 的 PRS 与对侧乳腺癌 (CBC) 风险之间的关联。我们纳入了 1990 年以来首次诊断出患有浸润性乳腺癌的 56,068 名欧洲血统女性，并由乳腺癌协会联盟进行了随访。使用 Cox 回归分析对根据 PRS 313分布的异时 CBC 风险 (N = 1,027) 进行量化。我们评估了 PRS 313与首次诊断年龄、家族史、形态学、ER 状态、PR 状态和 HER2 状态以及（新）辅助治疗的相互作用。在针对亚洲女性的研究中，随访有限，使用逻辑回归对 340 名 CBC 女性和 12,133 名单侧乳腺癌女性进行逻辑回归评估与 PRS 313相关的 CBC 风险。 PRS 313较高与 CBC 风险增加相关：欧洲人每标准差 (SD) 的风险比 = 1.25 (95%CI = 1.18–1.33)，亚洲人每 SD 的 OR = 1.15 (95%CI = 1.02–1.29) 。 PRS 313中欧洲女性的 CBC 终生绝对风险（将死亡作为竞争风险）在第10 个百分位时为 12.4%，在第 90个百分位时为 20.5%。我们没有发现任何证据表明个体特征、原发肿瘤特征或治疗存在混淆或相互作用。仅 PRS 313的 C 指数为 0.563 (95% CI = 0.547–0.586)。 总之，PRS 313是与 CBC 风险相关的独立因素，可以纳入 CBC 风险预测模型，以帮助改善分层并优化监测和治疗策略。
京公网安备 11010802027423号