| Literature DB >> 28283652 |
Hermela Shimelis1, Romy L S Mesman2, Catharina Von Nicolai3, Asa Ehlen3, Lucia Guidugli4, Charlotte Martin5, Fabienne M G R Calléja2, Huong Meeks6, Emily Hallberg7, Jamie Hinton7, Jenna Lilyquist7, Chunling Hu1, Cora M Aalfs8, Kristiina Aittomäki9, Irene Andrulis10,11, Hoda Anton-Culver12, Volker Arndt13, Matthias W Beckmann14, Javier Benitez15,16, Natalia V Bogdanova17,18, Stig E Bojesen19,20,21, Manjeet K Bolla22, Anne-Lise Borresen-Dale23,24, Hiltrud Brauch25,26,27, Paul Brennan28, Hermann Brenner13,27,29, Annegien Broeks30, Barbara Brouwers31,32, Thomas Brüning33, Barbara Burwinkel34,35, Jenny Chang-Claude36,37, Georgia Chenevix-Trench, Ching-Yu Cheng38, Ji-Yeob Choi39,40, J Margriet Collée41, Angela Cox42, Simon S Cross43, Kamila Czene44, Hatef Darabi44, Joe Dennis22, Thilo Dörk18, Isabel Dos-Santos-Silva45, Alison M Dunning46, Peter A Fasching14,47, Jonine Figueroa48,49, Henrik Flyger50, Montserrat García-Closas49, Graham G Giles51,52, Gord Glendon10, Pascal Guénel53, Christopher A Haiman54, Per Hall44, Ute Hamann55, Mikael Hartman56,57, Frans B Hogervorst30, Antoinette Hollestelle58, John L Hopper52, Hidemi Ito59,60, Anna Jakubowska61, Daehee Kang39,40,62, Veli-Matti Kosma63,64,65, Vessela Kristensen, Kah-Nyin Lai66,67, Diether Lambrechts68,69, Loic Le Marchand70, Jingmei Li44, Annika Lindblom71, Artitaya Lophatananon72, Jan Lubinski61, Eva Machackova73, Arto Mannermaa63,64,65, Sara Margolin74, Frederik Marme34,75, Keitaro Matsuo60,76, Hui Miao56, Kyriaki Michailidou22,77, Roger L Milne51,52, Kenneth Muir72,78, Susan L Neuhausen79, Heli Nevanlinna80, Janet E Olson7, Curtis Olswold7, Jan J C Oosterwijk81, Ana Osorio15,16, Paolo Peterlongo82, Julian Peto45, Paul D P Pharoah22,46, Katri Pylkäs83,84, Paolo Radice85, Muhammad Usman Rashid55,86, Valerie Rhenius46, Anja Rudolph36, Suleeporn Sangrajrang87, Elinor J Sawyer88, Marjanka K Schmidt30, Minouk J Schoemaker89,90, Caroline Seynaeve58, Mitul Shah46, Chen-Yang Shen91,92, Martha Shrubsole93, Xiao-Ou Shu93, Susan Slager7, Melissa C Southey94, Daniel O Stram54, Anthony Swerdlow89,90, Soo H Teo66,67, Ian Tomlinson95, Diana Torres55,96, Thérèse Truong53, Christi J van Asperen8, Lizet E van der Kolk30, Qin Wang22, Robert Winqvist83,84, Anna H Wu54, Jyh-Cherng Yu97, Wei Zheng93, Ying Zheng98, Jennifer Leary99, Logan Walker100, Lenka Foretova73, Florentia Fostira101, Kathleen B M Claes102, Liliana Varesco103, Setareh Moghadasi8, Douglas F Easton22,46, Amanda Spurdle104, Peter Devilee2, Harry Vrieling2, Alvaro N A Monteiro105,106, David E Goldgar107, Aura Carreira3, Maaike P G Vreeswijk2, Fergus J Couch108,7.
Abstract
Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28283652 PMCID： PMC5508554 DOI： 10.1158/0008-5472.CAN-16-2568
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701