RT Journal Article SR Electronic T1 Cancer risks in BRCA2 families: estimates for sites other than breast and ovary JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 711 OP 719 DO 10.1136/jmg.2004.028829 VO 42 IS 9 A1 C J van Asperen A1 R M Brohet A1 E J Meijers-Heijboer A1 N Hoogerbrugge A1 S Verhoef A1 H F A Vasen A1 M G E M Ausems A1 F H Menko A1 E B Gomez Garcia A1 J G M Klijn A1 F B L Hogervorst A1 J C van Houwelingen A1 L J van’t Veer A1 M A Rookus A1 F E van Leeuwen YR 2005 UL http://jmg.bmj.com/content/42/9/711.abstract 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.