title: CHEK2*1100delC homozygosity in the Netherlands--prevalence and risk of breast and lung cancer.
abstract: The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4-32.6, P=0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency.
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Petra E A
authors: PE
authors: Huijts
authors: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Antoinette
authors: A
authors: Hollestelle
authors: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Brunilda
authors: B
authors: Balliu
authors: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Jeanine J
authors: JJ
authors: Houwing-Duistermaat
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Caro M
authors: CM
authors: Meijers
authors: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Jannet C
authors: JC
authors: Blom
authors: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Bahar
authors: B
authors: Ozturk
authors: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors: Elly M M
authors: EM
authors: Krol-Warmerdam
authors: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Juul
authors: J
authors: Wijnen
authors: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Els M J J
authors: EM
authors: Berns
authors: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: John W M
authors: JW
authors: Martens
authors: Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Caroline
authors: C
authors: Seynaeve
authors: Department of Epidemiology, Biostatistics and HTA, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Lambertus A
authors: LA
authors: Kiemeney
authors: Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Henricus F
authors: HF
authors: van der Heijden
authors: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors: Rob A E M
authors: RA
authors: Tollenaar
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Peter
authors: P
authors: Devilee
authors: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Christi J
authors: CJ
authors: van Asperen
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D010375:Pedigree; D012307:Risk Factors
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human
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