Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America.

The CHEK21100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK21100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK21100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK21100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK21100delC mutations in North American populations (compared with Northern Europe), rendering CHEK21100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted.