TY - JOUR T1 - No evidence that protein truncating variants in <em>BRIP1</em> are associated with breast cancer risk: implications for gene panel testing JF - Journal of Medical Genetics JO - J Med Genet SP - 298 LP - 309 DO - 10.1136/jmedgenet-2015-103529 VL - 53 IS - 5 AU - Douglas F Easton AU - Fabienne Lesueur AU - Brennan Decker AU - Kyriaki Michailidou AU - Jun Li AU - Jamie Allen AU - Craig Luccarini AU - Karen A Pooley AU - Mitul Shah AU - Manjeet K Bolla AU - Qin Wang AU - Joe Dennis AU - Jamil Ahmad AU - Ella R Thompson AU - Francesca Damiola AU - Maroulio Pertesi AU - Catherine Voegele AU - Noura Mebirouk AU - Nivonirina Robinot AU - Geoffroy Durand AU - Nathalie Forey AU - Robert N Luben AU - Shahana Ahmed AU - Kristiina Aittomäki AU - Hoda Anton-Culver AU - Volker Arndt AU - Australian Ovarian Cancer Study Group AU - Caroline Baynes AU - Matthias W Beckman AU - Javier Benitez AU - David Van Den Berg AU - William J Blot AU - Natalia V Bogdanova AU - Stig E Bojesen AU - Hermann Brenner AU - Jenny Chang-Claude AU - Kee Seng Chia AU - Ji-Yeob Choi AU - Don M Conroy AU - Angela Cox AU - Simon S Cross AU - Kamila Czene AU - Hatef Darabi AU - Peter Devilee AU - Mikael Eriksson AU - Peter A Fasching AU - Jonine Figueroa AU - Henrik Flyger AU - Florentia Fostira AU - Montserrat García-Closas AU - Graham G Giles AU - Gord Glendon AU - Anna González-Neira AU - Pascal Guénel AU - Christopher A Haiman AU - Per Hall AU - Steven N Hart AU - Mikael Hartman AU - Maartje J Hooning AU - Chia-Ni Hsiung AU - Hidemi Ito AU - Anna Jakubowska AU - Paul A James AU - Esther M John AU - Nichola Johnson AU - Michael Jones AU - Maria Kabisch AU - Daehee Kang AU - kConFab Investigators AU - Veli-Matti Kosma AU - Vessela Kristensen AU - Diether Lambrechts AU - Na Li AU - Lifepool Investigators AU - Annika Lindblom AU - Jirong Long AU - Artitaya Lophatananon AU - Jan Lubinski AU - Arto Mannermaa AU - Siranoush Manoukian AU - Sara Margolin AU - Keitaro Matsuo AU - Alfons Meindl AU - Gillian Mitchell AU - Kenneth Muir AU - NBCS Investigators AU - Ines Nevelsteen AU - Ans van den Ouweland AU - Paolo Peterlongo AU - Sze Yee Phuah AU - Katri Pylkäs AU - Simone M Rowley AU - Suleeporn Sangrajrang AU - Rita K Schmutzler AU - Chen-Yang Shen AU - Xiao-Ou Shu AU - Melissa C Southey AU - Harald Surowy AU - Anthony Swerdlow AU - Soo H Teo AU - Rob A E M Tollenaar AU - Ian Tomlinson AU - Diana Torres AU - Thérèse Truong AU - Celine Vachon AU - Senno Verhoef AU - Michelle Wong-Brown AU - Wei Zheng AU - Ying Zheng AU - Heli Nevanlinna AU - Rodney J Scott AU - Irene L Andrulis AU - Anna H Wu AU - John L Hopper AU - Fergus J Couch AU - Robert Winqvist AU - Barbara Burwinkel AU - Elinor J Sawyer AU - Marjanka K Schmidt AU - Anja Rudolph AU - Thilo Dörk AU - Hiltrud Brauch AU - Ute Hamann AU - Susan L Neuhausen AU - Roger L Milne AU - Olivia Fletcher AU - Paul D P Pharoah AU - Ian G Campbell AU - Alison M Dunning AU - Florence Le Calvez-Kelm AU - David E Goldgar AU - Sean V Tavtigian AU - Georgia Chenevix-Trench Y1 - 2016/05/01 UR - http://jmg.bmj.com/content/53/5/298.abstract N2 - Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction.Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia.Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75).Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels. ER -