CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women

M.A. Adank, M.A. Jonker, I Kluijt, S.E. van Mil, R.A. Oldenburg, W.J. Mooi, F.B.L. Hogervorst, A.M.W. van den Ouweland, J.J.P. Gille, M.K. Schmidt, A.W. van der Vaart, E.J. Meijers-Heijboer, Q. Waisfisz

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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. 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. 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
Original languageEnglish
Pages (from-to)860-863
JournalJournal of medical genetics
Issue number12
Publication statusPublished - 2011

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