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

• Published in: European journal of cancer (1990) Vol. 41; no. 12; pp. 1819 - 1823
• Main Authors: de Jong, Mirjam M., Nolte, Ilja M., te Meerman, Gerard J., van der Graaf, Winette T.A., Oosterom, Elvira, Bruinenberg, Marcel, Steege, Gerrit van der, Oosterwijk, Jan C., van der Hout, Annemarie H., Boezen, H. Marike, Schaapveld, Michael, Kleibeuker, Jan H., de Vries, Elisabeth G.E.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.08.2005; Elsevier
• Subjects: 1100delC mutation; Adult; Aged; Analysis of Variance; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Checkpoint Kinase 2; CHEK2; Female; Genetic Predisposition to Disease - genetics; Genotype; HLA Antigens - genetics; HLA class III region; Humans; Medical sciences; Middle Aged; Mutation - genetics; Pharmacology. Drug treatments; Protein-Serine-Threonine Kinases - genetics; Risk Factors; Sporadic; Tumors; Breast cancer; HLA class III region; Sporadic; CHEK2; 1100delC mutation; HLA-System; Major histocompatibility system; Genotype; Pharmacology; Malignant tumor; Epidemiology; Mammary gland diseases; Cancerology; CHEK2: 1100delC mutation; Risk factor; Genetics; Mutation
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2005.04.035

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.