Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

Importance: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.

Objective: To identify mutation-specific cancer risks for carriers of BRCA1/2.

Design, Setting, And Participants: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations.

Spontaneous pneumothorax as indicator for Birt-Hogg-Dubé syndrome in paediatric patients.

Background: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominantly inherited disorder caused by germline mutations in the folliculin (FLCN) gene. Clinical manifestations of BHD include skin fibrofolliculomas, renal cell cancer, lung cysts and (recurrent) spontaneous pneumothorax (SP). All clinical manifestations usually present in adults > 20 years of age.

Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.