PT - JOURNAL ARTICLE AU - C J van Asperen AU - R M Brohet AU - E J Meijers-Heijboer AU - N Hoogerbrugge AU - S Verhoef AU - H F A Vasen AU - M G E M Ausems AU - F H Menko AU - E B Gomez Garcia AU - J G M Klijn AU - F B L Hogervorst AU - J C van Houwelingen AU - L J van’t Veer AU - M A Rookus AU - F E van Leeuwen TI - Cancer risks in <em>BRCA2</em> families: estimates for sites other than breast and ovary AID - 10.1136/jmg.2004.028829 DP - 2005 Sep 01 TA - Journal of Medical Genetics PG - 711--719 VI - 42 IP - 9 4099 - http://jmg.bmj.com/content/42/9/711.short 4100 - http://jmg.bmj.com/content/42/9/711.full SO - J Med Genet2005 Sep 01; 42 AB - Background: In BRCA2 mutation carriers, increased risks have been reported for several cancer sites besides breast and ovary. As most of the families included in earlier reports were selected on the basis of multiple breast/ovarian cancer cases, it is possible that risk estimates may differ in mutation carriers with a less striking family history. Methods: In the Netherlands, 139 BRCA2 families with 66 different pathogenic mutations were included in a nationwide study. To avoid testing bias, we chose not to estimate risk in typed carriers, but rather in male and female family members with a 50% prior probability of being a carrier (n = 1811). The relative risk (RR) for each cancer site with the exception of breast and ovarian cancer was determined by comparing observed numbers with those expected, based on Dutch cancer incidence rates. Results: We observed an excess risk for four cancer sites: pancreas (RR 5.9; 95% confidence interval (CI) 3.2 to 10.0), prostate (2.5; 1.6 to 3.8), bone (14.4; 2.9 to 42.1) and pharynx (7.3; 2.0 to 18.6). A small increase was observed for cancer of the digestive tract (1.5; 1.1 to 1.9). Histological verification was available for 46% of the tumours. Nearly all increased risks reached statistical significance for men only. Cancer risks tended to be higher for people before the age of 65 years. Moreover, families with mutations outside the previously defined ovarian cancer cluster region tended to have a higher cancer risk. Conclusions: We found that BRCA2 carriers are at increased risk for cancers of the prostate and pancreas, and possibly bone and pharynx. Larger databases with extended follow up are needed to provide insight into mutation specific risks of selected carriers in BRCA2 families.