No increased susceptibility to breast cancer from combined CHEK2 1100delC genotype and the HLA class III region risk factors

Mirjam de Jong, Ilja Nolte, Gerhardus te Meerman, WTA van der Graaf, E Oosterom, M Bruinenberg, G van der Steege, JC Oosterwijk, Annemarie van der Hout, HM Boezen, M Schaapveld, JH Kleibeuker, EGE de Vries*

*Corresponding author for this work

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CHEK2 is low-penetrance breast cancer susceptibility gene. The 1100delC mutation may interact with variants/mutations in other breast cancer susceptibility loci. We identified a risk haplotype in the HLA class III region in breast cancer patients [de Jong MM, Nolte IM, de Vries EGE, et al. The HLA class III subregion is responsible for an increased breast cancer risk. Hum Mol Genet 2003, 12, 2311-2319] and tested whether it interacted with 1100delC mutation.

The CHEK2 1100delC mutation was analysed in the same series of patients and controls as in the HLA breast cancer study. In 962 unselected breast cancer patients, the 1100delC mutation was observed in 2.9% and in 367 controls in 1.4% (NS). The highest 1100delC frequency occurred in high-risk (4.4%), followed by moderate-risk (3.8%), and lowest in low genetic risk patients (2.4%, P-trend 0.029). In HLA risk haplotype carriers no increased breast cancer risk was observed in the presence of 1100delC mutation. Patients more often had one than both genetic risk factors.

The 1100delC mutation and the HLA risk haplotype confer increased breast cancer risks, but an interactive effect on breast cancer between both factors is unlikely. In contrast, the effect of 1100delC mutation on breast cancer risk was limited to individuals without HLA risk haplotype, suggesting a mutual excluding effect between these risk factors. (C) 2005 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1819-1823
Number of pages5
JournalEuropean Journal of Cancer
Issue number12
Publication statusPublished - Aug-2005


  • breast cancer
  • CHEK2
  • 1100delC mutation
  • HLA class III region
  • sporadic
  • BRCA1
  • CHK2
  • P53
  • ATM

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