Journal Article

Breast-Cancer Risk in Families with Mutations in PALB2

Domchek, Susan M, Yannoukakos, Drakoulis, Tischkowitz, Marc, Pylkäs, Katri, Moilanen, Jukka S, Claes, Kathleen B.M, Aittomäki, Kristiina, Couch, Fergus J, Winqvist, Robert, Subramanian, Deepak, Tomiak, Eva, Mannermaa, Arto, Andrulis, Irene L, Toland, Amanda E, Casadei, Silvia, Turnbull, Clare, Seal, Sheila, Nevanlinna, Heli, Concannon, Patrick, Poppe, Bruce, Southey, Melissa C, Teo, Zhi L, Peterlongo, Paolo, Manoukian, Siranoush, Kallioniemi, Anne, Radice, Paolo, Khan, Sofia, Easton, Douglas F, Tondini, Carlo, Goldgar, David E, Neuhausen, Susan L, Hopper, John L, Roberts, Jonathan, Lee, Andrew, King, Mary-Claire, Foulkes, William D, Antoniou, Antonis C, James, Paul A, Buys, Saundra S, Weitzel, Jeffrey N, Fostira, Florentia, Rahman, Nazneen, De Leeneer, Kim, Bernstein, Jonine L, Barrowdale, Daniel, Heikkinen, Tuomas, Lindeman, Geoffrey J, Miron, Penelope

2014

Overview

A multinational study of 154 families with PALB2 mutations shows that mutation carriers have a 14% risk of breast cancer by 50 years of age and a 35% risk by 70 years of age, which is similar to the risk associated with BRCA2 mutations. PALB2 (partner and localizer of BRCA2) was originally identified as a BRCA2-interacting protein that is crucial for key BRCA2 genome caretaker functions 1 , 2 ; it was subsequently also shown to interact with BRCA1. 3 Biallelic germline loss-of-function mutations in PALB2 (also known as FANCN ) cause Fanconi’s anemia, whereas monoallelic loss-of-function mutations are associated with an increased risk of breast cancer and pancreatic cancer. 4 Previous studies of familial breast cancer have yielded estimates of risk in association with loss-of-function mutations in PALB2 that are two to four times as high as the risk among non–mutation carriers. 5 – 7 In Finland, the PALB2 . . .

• Publisher: Massachusetts Medical Society
• Subject: Adult / Age / Aged / Aged, 80 and over / Biological and medical sciences / BRCA2 protein / Breast cancer / Breast Neoplasms - congenital / Breast Neoplasms - genetics / Family medical history / Fanconi Anemia Complementation Group N Protein / Female / Gene deletion / General aspects / Genes / Genes, BRCA2 / Genetic Predisposition to Disease / Genotypes / Germ-Line Mutation / Gynecology. Andrology. Obstetrics / Heterozygote / Humans / Mammary gland diseases / Medical sciences / Middle Aged / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Mutation / Nuclear Proteins - genetics / Receptor, ErbB-2 - analysis / Receptors, Estrogen - analysis / Receptors, Progesterone - analysis / Risk / Risk factors / Sequence Deletion / Tumor Suppressor Proteins - genetics / Tumors / Women