Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing.
BACKGROUND
Population-based data on the risk of cancer in families eligible for BRCA1/2 mutation testing may help to reach a consensus about the association of BRCA1/2 mutations with cancer at sites other than the breast and may reveal new, non-BRCA1/2 related components of the familial clustering of cancer in those families.


METHODS
The families of the Swedish Family-Cancer Database with at least three generations (n = 944,723) were classified according to the criteria proposed by the German Consortium for Hereditary Breast and Ovarian Cancer. The cancer incidences in the classified families were compared with the incidences in the general population. The percentages of individuals with cancer in families eligible for BRCA1/2 mutation testing were compared with data in the literature to estimate the proportion of malignancies related to BRCA1/2 mutations.


RESULTS
Families with two breast cancers before the age of 50 years showed increased risk of early onset pancreatic, prostate and ovarian cancers; families with ovarian and breast cancers presented increased incidences for ovarian and ocular cancers; families with two breast cancers, at least one of them under the age of 50 years, showed increased risks of prostate and primary liver cancers. Stomach cancer before age 70 years was twice as frequent in families with breast and ovarian cancers as in the general population. BRCA1/2 mutations probably explain most of the aggregation of ovarian cancer in families with male breast cancer, and in families with at least two breast cancers diagnosed before age 50 years.


CONCLUSIONS
The association of BRCA1/2 mutations with ovarian, pancreatic, prostate and stomach cancers was confirmed at a population level. However, the clustering of early pancreatic cancer in families with two breast cancers under age 50 years, the aggregation of ovarian cancer in families with breast and ovarian cancers, and the increased incidence of early onset prostate cancer in families with male breast cancer seem to be due to other effects unrelated to BRCA1/2 mutations.
Lorenzo Bermejo
J
J
Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany. J.Lorenzo@dkfz.de
Hemminki
K
K
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000235:genetics*; D004252:DNA Mutational Analysis; D016208:Databases, Factual; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000150:complications* / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics; D012042:Registries / Q000706:statistics & numerical data*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics; D013548:Sweden / Q000453:epidemiology