BACKGROUND: Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal. METHODS: Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146 326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci. RESULTS: Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low = 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29%, and 32% reductions in risk of invasive breast cancer in the low, intermediate, and high PRS groups, respectively (HRhigh vs low = 0.70, 95% CI = 0.56 to 0.88; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women. CONCLUSION: Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.
BACKGROUND:Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal. METHODS: Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146 326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci. RESULTS: Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low = 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29%, and 32% reductions in risk of invasive breast cancer in the low, intermediate, and high PRS groups, respectively (HRhigh vs low = 0.70, 95% CI = 0.56 to 0.88; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women. CONCLUSION: Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.
Authors: Celine M Vachon; V Shane Pankratz; Christopher G Scott; Lothar Haeberle; Elad Ziv; Matthew R Jensen; Kathleen R Brandt; Dana H Whaley; Janet E Olson; Katharina Heusinger; Carolin C Hack; Sebastian M Jud; Matthias W Beckmann; Ruediger Schulz-Wendtland; Jeffrey A Tice; Aaron D Norman; Julie M Cunningham; Kristen S Purrington; Douglas F Easton; Thomas A Sellers; Karla Kerlikowske; Peter A Fasching; Fergus J Couch Journal: J Natl Cancer Inst Date: 2015-03-04 Impact factor: 13.506
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Authors: Nasim Mavaddat; Kyriaki Michailidou; Joe Dennis; Michael Lush; Laura Fachal; Andrew Lee; Jonathan P Tyrer; Ting-Huei Chen; Qin Wang; Manjeet K Bolla; Xin Yang; Muriel A Adank; Thomas Ahearn; Kristiina Aittomäki; Jamie Allen; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Volker Arndt; Kristan J Aronson; Paul L Auer; Päivi Auvinen; Myrto Barrdahl; Laura E Beane Freeman; Matthias W Beckmann; Sabine Behrens; Javier Benitez; Marina Bermisheva; Leslie Bernstein; Carl Blomqvist; Natalia V Bogdanova; Stig E Bojesen; Bernardo Bonanni; Anne-Lise Børresen-Dale; Hiltrud Brauch; Michael Bremer; Hermann Brenner; Adam Brentnall; Ian W Brock; Angela Brooks-Wilson; Sara Y Brucker; Thomas Brüning; Barbara Burwinkel; Daniele Campa; Brian D Carter; Jose E Castelao; Stephen J Chanock; Rowan Chlebowski; Hans Christiansen; Christine L Clarke; J Margriet Collée; Emilie Cordina-Duverger; Sten Cornelissen; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Mary B Daly; Peter Devilee; Thilo Dörk; Isabel Dos-Santos-Silva; Martine Dumont; Lorraine Durcan; Miriam Dwek; Diana M Eccles; Arif B Ekici; A Heather Eliassen; Carolina Ellberg; Christoph Engel; Mikael Eriksson; D Gareth Evans; Peter A Fasching; Jonine Figueroa; Olivia Fletcher; Henrik Flyger; Asta Försti; Lin Fritschi; Marike Gabrielson; Manuela Gago-Dominguez; Susan M Gapstur; José A García-Sáenz; Mia M Gaudet; Vassilios Georgoulias; Graham G Giles; Irina R Gilyazova; Gord Glendon; Mark S Goldberg; David E Goldgar; Anna González-Neira; Grethe I Grenaker Alnæs; Mervi Grip; Jacek Gronwald; Anne Grundy; Pascal Guénel; Lothar Haeberle; Eric Hahnen; Christopher A Haiman; Niclas Håkansson; Ute Hamann; Susan E Hankinson; Elaine F Harkness; Steven N Hart; Wei He; Alexander Hein; Jane Heyworth; Peter Hillemanns; Antoinette Hollestelle; Maartje J Hooning; Robert N Hoover; John L Hopper; Anthony Howell; Guanmengqian Huang; Keith Humphreys; David J Hunter; Milena Jakimovska; Anna Jakubowska; Wolfgang Janni; Esther M John; Nichola Johnson; Michael E Jones; Arja Jukkola-Vuorinen; Audrey Jung; Rudolf Kaaks; Katarzyna Kaczmarek; Vesa Kataja; Renske Keeman; Michael J Kerin; Elza Khusnutdinova; Johanna I Kiiski; Julia A Knight; Yon-Dschun Ko; Veli-Matti Kosma; Stella Koutros; Vessela N Kristensen; Ute Krüger; Tabea Kühl; Diether Lambrechts; Loic Le Marchand; Eunjung Lee; Flavio Lejbkowicz; Jenna Lilyquist; Annika Lindblom; Sara Lindström; Jolanta Lissowska; Wing-Yee Lo; Sibylle Loibl; Jirong Long; Jan Lubiński; Michael P Lux; Robert J MacInnis; Tom Maishman; Enes Makalic; Ivana Maleva Kostovska; Arto Mannermaa; Siranoush Manoukian; Sara Margolin; John W M Martens; Maria Elena Martinez; Dimitrios Mavroudis; Catriona McLean; Alfons Meindl; Usha Menon; Pooja Middha; Nicola Miller; Fernando Moreno; Anna Marie Mulligan; Claire Mulot; Victor M Muñoz-Garzon; Susan L Neuhausen; Heli Nevanlinna; Patrick Neven; William G Newman; Sune F Nielsen; Børge G Nordestgaard; Aaron Norman; Kenneth Offit; Janet E Olson; Håkan Olsson; Nick Orr; V Shane Pankratz; Tjoung-Won Park-Simon; Jose I A Perez; Clara Pérez-Barrios; Paolo Peterlongo; Julian Peto; Mila Pinchev; Dijana Plaseska-Karanfilska; Eric C Polley; Ross Prentice; Nadege Presneau; Darya Prokofyeva; Kristen Purrington; Katri Pylkäs; Brigitte Rack; Paolo Radice; Rohini Rau-Murthy; Gad Rennert; Hedy S Rennert; Valerie Rhenius; Mark Robson; Atocha Romero; Kathryn J Ruddy; Matthias Ruebner; Emmanouil Saloustros; Dale P Sandler; Elinor J Sawyer; Daniel F Schmidt; Rita K Schmutzler; Andreas Schneeweiss; Minouk J Schoemaker; Fredrick Schumacher; Peter Schürmann; Lukas Schwentner; Christopher Scott; Rodney J Scott; Caroline Seynaeve; Mitul Shah; Mark E Sherman; Martha J Shrubsole; Xiao-Ou Shu; Susan Slager; Ann Smeets; Christof Sohn; Penny Soucy; Melissa C Southey; John J Spinelli; Christa Stegmaier; Jennifer Stone; Anthony J Swerdlow; Rulla M Tamimi; William J Tapper; Jack A Taylor; Mary Beth Terry; Kathrin Thöne; Rob A E M Tollenaar; Ian Tomlinson; Thérèse Truong; Maria Tzardi; Hans-Ulrich Ulmer; Michael Untch; Celine M Vachon; Elke M van Veen; Joseph Vijai; Clarice R Weinberg; Camilla Wendt; Alice S Whittemore; Hans Wildiers; Walter Willett; Robert Winqvist; Alicja Wolk; Xiaohong R Yang; Drakoulis Yannoukakos; Yan Zhang; Wei Zheng; Argyrios Ziogas; Alison M Dunning; Deborah J Thompson; Georgia Chenevix-Trench; Jenny Chang-Claude; Marjanka K Schmidt; Per Hall; Roger L Milne; Paul D P Pharoah; Antonis C Antoniou; Nilanjan Chatterjee; Peter Kraft; Montserrat García-Closas; Jacques Simard; Douglas F Easton Journal: Am J Hum Genet Date: 2018-12-13 Impact factor: 11.025
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