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Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.


ABSTRACT: Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P?-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate?

SUBMITTER: Zhang H 

PROVIDER: S-EPMC7808397 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Zhang Haoyu H   Ahearn Thomas U TU   Lecarpentier Julie J   Barnes Daniel D   Beesley Jonathan J   Qi Guanghao G   Jiang Xia X   O'Mara Tracy A TA   Zhao Ni N   Bolla Manjeet K MK   Dunning Alison M AM   Dennis Joe J   Wang Qin Q   Ful Zumuruda Abu ZA   Aittomäki Kristiina K   Andrulis Irene L IL   Anton-Culver Hoda H   Arndt Volker V   Aronson Kristan J KJ   Arun Banu K BK   Auer Paul L PL   Azzollini Jacopo J   Barrowdale Daniel D   Becher Heiko H   Beckmann Matthias W MW   Behrens Sabine S   Benitez Javier J   Bermisheva Marina M   Bialkowska Katarzyna K   Blanco Ana A   Blomqvist Carl C   Bogdanova Natalia V NV   Bojesen Stig E SE   Bonanni Bernardo B   Bondavalli Davide D   Borg Ake A   Brauch Hiltrud H   Brenner Hermann H   Briceno Ignacio I   Broeks Annegien A   Brucker Sara Y SY   Brüning Thomas T   Burwinkel Barbara B   Buys Saundra S SS   Byers Helen H   Caldés Trinidad T   Caligo Maria A MA   Calvello Mariarosaria M   Campa Daniele D   Castelao Jose E JE   Chang-Claude Jenny J   Chanock Stephen J SJ   Christiaens Melissa M   Christiansen Hans H   Chung Wendy K WK   Claes Kathleen B M KBM   Clarke Christine L CL   Cornelissen Sten S   Couch Fergus J FJ   Cox Angela A   Cross Simon S SS   Czene Kamila K   Daly Mary B MB   Devilee Peter P   Diez Orland O   Domchek Susan M SM   Dörk Thilo T   Dwek Miriam M   Eccles Diana M DM   Ekici Arif B AB   Evans D Gareth DG   Fasching Peter A PA   Figueroa Jonine J   Foretova Lenka L   Fostira Florentia F   Friedman Eitan E   Frost Debra D   Gago-Dominguez Manuela M   Gapstur Susan M SM   Garber Judy J   García-Sáenz José A JA   Gaudet Mia M MM   Gayther Simon A SA   Giles Graham G GG   Godwin Andrew K AK   Goldberg Mark S MS   Goldgar David E DE   González-Neira Anna A   Greene Mark H MH   Gronwald Jacek J   Guénel Pascal P   Häberle Lothar L   Hahnen Eric E   Haiman Christopher A CA   Hake Christopher R CR   Hall Per P   Hamann Ute U   Harkness Elaine F EF   Heemskerk-Gerritsen Bernadette A M BAM   Hillemanns Peter P   Hogervorst Frans B L FBL   Holleczek Bernd B   Hollestelle Antoinette A   Hooning Maartje J MJ   Hoover Robert N RN   Hopper John L JL   Howell Anthony A   Huebner Hanna H   Hulick Peter J PJ   Imyanitov Evgeny N EN   Isaacs Claudine C   Izatt Louise L   Jager Agnes A   Jakimovska Milena M   Jakubowska Anna A   James Paul P   Janavicius Ramunas R   Janni Wolfgang W   John Esther M EM   Jones Michael E ME   Jung Audrey A   Kaaks Rudolf R   Kapoor Pooja Middha PM   Karlan Beth Y BY   Keeman Renske R   Khan Sofia S   Khusnutdinova Elza E   Kitahara Cari M CM   Ko Yon-Dschun YD   Konstantopoulou Irene I   Koppert Linetta B LB   Koutros Stella S   Kristensen Vessela N VN   Laenkholm Anne-Vibeke AV   Lambrechts Diether D   Larsson Susanna C SC   Laurent-Puig Pierre P   Lazaro Conxi C   Lazarova Emilija E   Lejbkowicz Flavio F   Leslie Goska G   Lesueur Fabienne F   Lindblom Annika A   Lissowska Jolanta J   Lo Wing-Yee WY   Loud Jennifer T JT   Lubinski Jan J   Lukomska Alicja A   MacInnis Robert J RJ   Mannermaa Arto A   Manoochehri Mehdi M   Manoukian Siranoush S   Margolin Sara S   Martinez Maria Elena ME   Matricardi Laura L   McGuffog Lesley L   McLean Catriona C   Mebirouk Noura N   Meindl Alfons A   Menon Usha U   Miller Austin A   Mingazheva Elvira E   Montagna Marco M   Mulligan Anna Marie AM   Mulot Claire C   Muranen Taru A TA   Nathanson Katherine L KL   Neuhausen Susan L SL   Nevanlinna Heli H   Neven Patrick P   Newman William G WG   Nielsen Finn C FC   Nikitina-Zake Liene L   Nodora Jesse J   Offit Kenneth K   Olah Edith E   Olopade Olufunmilayo I OI   Olsson Håkan H   Orr Nick N   Papi Laura L   Papp Janos J   Park-Simon Tjoung-Won TW   Parsons Michael T MT   Peissel Bernard B   Peixoto Ana A   Peshkin Beth B   Peterlongo Paolo P   Peto Julian J   Phillips Kelly-Anne KA   Piedmonte Marion M   Plaseska-Karanfilska Dijana D   Prajzendanc Karolina K   Prentice Ross R   Prokofyeva Darya D   Rack Brigitte B   Radice Paolo P   Ramus Susan J SJ   Rantala Johanna J   Rashid Muhammad U MU   Rennert Gad G   Rennert Hedy S HS   Risch Harvey A HA   Romero Atocha A   Rookus Matti A MA   Rübner Matthias M   Rüdiger Thomas T   Saloustros Emmanouil E   Sampson Sarah S   Sandler Dale P DP   Sawyer Elinor J EJ   Scheuner Maren T MT   Schmutzler Rita K RK   Schneeweiss Andreas A   Schoemaker Minouk J MJ   Schöttker Ben B   Schürmann Peter P   Senter Leigha L   Sharma Priyanka P   Sherman Mark E ME   Shu Xiao-Ou XO   Singer Christian F CF   Smichkoska Snezhana S   Soucy Penny P   Southey Melissa C MC   Spinelli John J JJ   Stone Jennifer J   Stoppa-Lyonnet Dominique D   Swerdlow Anthony J AJ   Szabo Csilla I CI   Tamimi Rulla M RM   Tapper William J WJ   Taylor Jack A JA   Teixeira Manuel R MR   Terry MaryBeth M   Thomassen Mads M   Thull Darcy L DL   Tischkowitz Marc M   Toland Amanda E AE   Tollenaar Rob A E M RAEM   Tomlinson Ian I   Torres Diana D   Troester Melissa A MA   Truong Thérèse T   Tung Nadine N   Untch Michael M   Vachon Celine M CM   van den Ouweland Ans M W AMW   van der Kolk Lizet E LE   van Veen Elke M EM   vanRensburg Elizabeth J EJ   Vega Ana A   Wappenschmidt Barbara B   Weinberg Clarice R CR   Weitzel Jeffrey N JN   Wildiers Hans H   Winqvist Robert R   Wolk Alicja A   Yang Xiaohong R XR   Yannoukakos Drakoulis D   Zheng Wei W   Zorn Kristin K KK   Milne Roger L RL   Kraft Peter P   Simard Jacques J   Pharoah Paul D P PDP   Michailidou Kyriaki K   Antoniou Antonis C AC   Schmidt Marjanka K MK   Chenevix-Trench Georgia G   Easton Douglas F DF   Chatterjee Nilanjan N   García-Closas Montserrat M  

Nature genetics 20200518 6


Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype<sup>1-3</sup>. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor  ...[more]

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