PT  - JOURNAL ARTICLE
AU  - Adank, Muriel A
AU  - Jonker, Marianne A
AU  - Kluijt, Irma
AU  - van Mil, Saskia E
AU  - Oldenburg, Rogier A
AU  - Mooi, Wolter J
AU  - Hogervorst, Frans B L
AU  - van den Ouweland, Ans M W
AU  - Gille, Johan J P
AU  - Schmidt, Marjanka K
AU  - van der Vaart, Aad W
AU  - Meijers-Heijboer, Hanne
AU  - Waisfisz, Quinten
TI  - <em>CHEK2</em>*1100delC homozygosity is associated with a high breast cancer risk in women
AID  - 10.1136/jmedgenet-2011-100380
DP  - 2011 Dec 01
TA  - Journal of Medical Genetics
PG  - 860--863
VI  - 48
IP  - 12
4099  - http://jmg.bmj.com/content/48/12/860.short
4100  - http://jmg.bmj.com/content/48/12/860.full
SO  - J Med Genet2011 Dec 01; 48
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.