RT Journal Article SR Electronic T1 CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 860 OP 863 DO 10.1136/jmedgenet-2011-100380 VO 48 IS 12 A1 Muriel A Adank A1 Marianne A Jonker A1 Irma Kluijt A1 Saskia E van Mil A1 Rogier A Oldenburg A1 Wolter J Mooi A1 Frans B L Hogervorst A1 Ans M W van den Ouweland A1 Johan J P Gille A1 Marjanka K Schmidt A1 Aad W van der Vaart A1 Hanne Meijers-Heijboer A1 Quinten Waisfisz YR 2011 UL http://jmg.bmj.com/content/48/12/860.abstract AB Background Mutations in the CHEK2 gene confer a moderately increased breast cancer risk. The risk for female carriers of the CHEK2*1100delC mutation is twofold increased. Breast cancer risk for carrier women is higher in a familial breast cancer setting which is due to coinheritance of additional genetic risk factors. This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk.Methods and results Homozygosity for the CHEK2*1100delC allele was identified in 8/2554 Dutch independent familial non-BRCA1/2 breast cancer cases. The genotype relative risk for breast cancer of homozygous and heterozygous familial breast cancer cases was 101.34 (95% CI 4.47 to 121 000) and 4.04 (95% CI 0.88 to 21.0), respectively. Female homozygotes appeared to have a greater than twofold increased breast cancer risk compared to familial CHEK2*1100delC heterozygotes (p=0.044). These results and the occurrence of multiple primary tumours in 7/10 homozygotes indicate a high cancer risk in homozygous women from non-BRCA1/2 families.Conclusions Intensive breast surveillance is therefore justified in these homozygous women. It is concluded that diagnostic testing for biallelic mutations in CHEK2 is indicated in non-BRCA1/2 breast cancer families, especially in populations with a relatively high prevalence of deleterious mutations in CHEK2.