a palb2 mutation associated with high risk of breast cancer一个palb2基因突变与乳腺癌的风险很高.pdfVIP

Southey et al. Breast Cancer Research 2010, 12:R109 /content/12/6/R109 RESEARCH ARTICLE Open Access A PALB2 mutation associated with high risk of breast cancer 1 1 2 1 1 3,4 Melissa C Southey , Zhi L Teo , James G Dowty , Fabrice A Odefrey , Daniel J Park , Marc Tischkowitz , 3 2 5 6 2,7 2,7 Nelly Sabbaghian , Carmel Apicella , Graham B Byrnes , Ingrid Winship , Laura Baglietto , Graham G Giles , 8 3,4 2* 9 David E Goldgar , William D Foulkes , John L Hopper , kConFab , for the Breast Cancer Family Registry Abstract Introduction: As a group, women who carry germline mutations in partner and localizer of breast cancer 2 susceptibility protein (PALB2) are at increased risk of breast cancer. Little is known about by how much or whether risk differs by mutation or family history, owing to the paucity of studies of cases unselected for family history. Methods: We screened 1,403 case probands for PALB2 mutations in a population-based study of Australian women with invasive breast cancer stratified by age at onset. The age-specific risk of breast cancer was estimated from the cancer histories of first- and second-degree relatives of mutation-carrying probands using a modified segregation analysis that included a polygenic modifier and was conditioned on the carrier case proband. Further screening for PALB2 c.3113G A (W1038X) was conducted for 779 families with multiple cases of breast cancer ascertained through family cancer clinics in