Combined associations of a polygenic risk score and classical risk factors with breast cancer risk.

Authors:
Pooja Middha Kapoor Nasim Mavaddat Parichoy Pal Choudhury Amber N Wilcox Sara Lindström Sabine Behrens Kyriaki Michailidou Joe Dennis Manjeet K Bolla Qin Wang Audrey Jung Zomoroda Abu-Ful Thomas Ahearn Irene L Andrulis Hoda Anton-Culver Volker Arndt Kristan J Aronson Paul L Auer Laura E Beane Freeman Heiko Becher Matthias W Beckmann Alicia Beeghly-Fadiel Javier Benitez Leslie Bernstein Stig E Bojesen Hiltrud Brauch Hermann Brenner Thomas Brüning Qiuyin Cai Daniele Campa Federico Canzian Angel Carracedo Brian D Carter Jose E Castelao Stephen J Chanock Nilanjan Chatterjee Georgia Chenevix-Trench Christine L Clarke Fergus J Couch Angela Cox Simon S Cross Kamila Czene James Y Dai H Shelton Earp Arif B Ekici A Heather Eliassen Mikael Eriksson D Gareth Evans Peter A Fasching Jonine Figueroa Lin Fritschi Marike Gabrielson Manuela Gago-Dominguez Chi Gao Susan M Gapstur Mia M Gaudet Graham G Giles Anna González-Neira Pascal Guénel Lothar Haeberle Christopher A Haiman Niclas Håkansson Per Hall Ute Hamann Sigrid Hatse Jane Heyworth Bernd Holleczek Robert N Hoover John L Hopper Anthony Howell David J Hunter Esther M John Michael E Jones Rudolf Kaaks Renske Keeman Cari M Kitahara Yon-Dschun Ko Stella Koutros Allison W Kurian Diether Lambrechts Loic Le Marchand Eunjung Lee Flavio Lejbkowicz Martha Linet Jolanta Lissowska Ana Llaneza Robert J MacInnis Maria Elena Martinez Tabea Maurer Catriona McLean Susan L Neuhausen William G Newman Aaron Norman Katie M O'Brien Andrew F Olshan Janet E Olson Håkan Olsson Nick Orr Charles M Perou Guillermo Pita Eric C Polley Ross L Prentice Gad Rennert Hedy S Rennert Kathryn J Ruddy Dale P Sandler Christobel Saunders Minouk J Schoemaker Ben Schöttker Fredrick Schumacher Christopher Scott Rodney J Scott Xiao-Ou Shu Ann Smeets Melissa C Southey John J Spinelli Jennifer Stone Anthony J Swerdlow Rulla M Tamimi Jack A Taylor Melissa A Troester Celine M Vachon Elke M van Veen Xiaoliang Wang Clarice R Weinberg Caroline Weltens Walter Willett Stacey J Winham Alicja Wolk Xiaohong R Yang Wei Zheng Argyrios Ziogas Alison M Dunning Paul D P Pharoah Marjanka K Schmidt Peter Kraft Douglas F Easton Roger L Milne Montserrat García-Closas Jenny Chang-Claude

J Natl Cancer Inst 2020 May 2. Epub 2020 May 2.

Division of Cancer Epidemiology. German Cancer Research Center (DKFZ). Heidelberg: Germany.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djaa056DOI Listing
May 2020
12.583 Impact Factor

Publication Analysis

Top Keywords

breast cancer
24
risk factors
16
risk
13
cancer risk
12
risk breast
8
genetic risk
8
classical risk
8
cancer
6
breast
6
risk prs313
4
evidence per-standard
4
status accounting
4
per-standard deviation
4
higher genetic
4
accounting multiple
4
receptor status
4
find evidence
4
women higher
4
testing find
4
multiple testing
4

Similar Publications