RT Journal Article
SR Electronic
T1 <em>CHEK2</em>*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 Adank, Muriel A
A1 Jonker, Marianne A
A1 Kluijt, Irma
A1 van Mil, Saskia E
A1 Oldenburg, Rogier A
A1 Mooi, Wolter J
A1 Hogervorst, Frans B L
A1 van den Ouweland, Ans M W
A1 Gille, Johan J P
A1 Schmidt, Marjanka K
A1 van der Vaart, Aad W
A1 Meijers-Heijboer, Hanne
A1 Waisfisz, Quinten
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.