Journal Article

CHEK21100delC homozygosity is associated with a high breast cancer risk in women

Kluijt, Irma, van den Ouweland, Ans M W, Gille, Johan J P, van der Vaart, Aad W, Oldenburg, Rogier A, Meijers-Heijboer, Hanne, Waisfisz, Quinten, Schmidt, Marjanka K, Mooi, Wolter J, Hogervorst, Frans B L, van Mil, Saskia E, Adank, Muriel A, Jonker, Marianne A

2011

Overview

BackgroundMutations 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 resultsHomozygosity 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.ConclusionsIntensive 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.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Adult / Aged / Alleles / Biological and medical sciences / BRCA1 Protein - genetics / BRCA2 Protein - genetics / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - pathology / cancer risk / cancer: breast / cancer: colon / Checkpoint Kinase 2 / CHEK2 / CHEK21100delC / clinical genetics / Diagnostics tests / epidemiology / Female / Frameshift Mutation / Genetic Carrier Screening / genetic epidemiology / Genetic Predisposition to Disease / genetic screening/counselling / Genetic Testing / genetics / Gynecology. Andrology. Obstetrics / Heterozygote / Homozygote / Humans / Male / Mammary gland diseases / Medical sciences / Middle Aged / molecular genetics / Pedigree / Protein-Serine-Threonine Kinases - genetics / Risk Factors / Tumors