Genetic modifiers of CHEK2∗1100delC-associated breast cancer risk

TA Muranen; D Greco; C Blomqvist; K Aittomäki; S Khan; F Hogervorst; S Verhoef; PDP Pharoah; AM Dunning; M Shah; R Luben; SE Bojesen; BG Nordestgaard; M Schoemaker; A Swerdlow; M García-Closas; J Figueroa; T Dörk; NV Bogdanova; P Hall; J Li; E Khusnutdinova; M Bermisheva; V Kristensen; AL Borresen-Dale; N Investigators; J Peto; I Dos Santos Silva; FJ Couch; JE Olson; P Hillemans; TW Park-Simon; H Brauch; U Hamann; B Burwinkel; F Marme; A Meindl; RK Schmutzler; A Cox; SS Cross; EJ Sawyer; I Tomlinson; D Lambrechts; M Moisse; A Lindblom; S Margolin; A Hollestelle; JWM Martens; PA Fasching; MW Beckmann; IL Andrulis; JA Knight; H Anton-Culver; A Ziogas; GG Giles; RL Milne; H Brenner; V Arndt; A Mannermaa; VM Kosma; J Chang-Claude; A Rudolph; P Devilee; C Seynaeve; JL Hopper; MC Southey; EM John; AS Whittemore; MK Bolla; Q Wang; K Michailidou; J Dennis; DF Easton; MK Schmidt; H Nevanlinna

Journal article

Genetic modifiers of CHEK2∗1100delC-associated breast cancer risk

TA Muranen, D Greco, C Blomqvist, K Aittomäki, S Khan, F Hogervorst, S Verhoef, PDP Pharoah, AM Dunning, M Shah, R Luben, SE Bojesen, BG Nordestgaard, M Schoemaker, A Swerdlow, M García-Closas, J Figueroa, T Dörk, NV Bogdanova, P Hall Show all

Genetics in Medicine | NATURE PUBLISHING GROUP | Published : 2017

DOI: 10.1038/gim.2016.147

Abstract

Purpose:CHEK2∗1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2∗1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC).Methods:Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2∗1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction.Results:The PRS conferr..

View full abstract