Elsevier

Cancer Genetics

Volume 208, Issue 4, April 2015, Pages 129-134
Cancer Genetics

Original article
CHEK2 c.1100delC allele is rarely identified in Greek breast cancer cases

https://doi.org/10.1016/j.cancergen.2015.02.006Get rights and content

The CHEK2 gene encodes a protein kinase that plays a crucial role in maintenance of genomic integrity and the DNA repair mechanism. CHEK2 germline mutations are associated with increased risk of breast cancer and other malignancies. From a clinical perspective, the most significant mutation identified is the c.1100delC mutation, which is associated with an approximately 25% lifetime breast cancer risk. The distribution of this mutation shows wide geographical variation; it is more prevalent in the Northern European countries and less common, or even absent, in Southern Europe. In order to estimate the frequency of the CHEK2 c.1100delC mutation in Greek breast cancer patients, we genotyped 2,449 patients (2,408 females and 41 males), which was the largest series ever tested for c.1100delC. The mean age of female and male breast cancer diagnosis was 49 and 59 years, respectively. All patients had previously tested negative for the Greek BRCA1 founder and recurrent mutations. The CHEK2 c.1100delC mutation was detected in 0.16% (4 of 2,408) of females, all of whom were diagnosed with breast cancer before the age of 50 years. Only one c.1100delC carrier was reported with breast cancer family history. The present study indicates that the CHEK2 c.1100delC mutation does not contribute substantially to hereditary breast cancer in patients of Greek descent.

Section snippets

Patient study group

This study involved 2,449 subjects (2,408 females and 41 males), who were diagnosed with breast cancer and were enrolled from several hospitals in Greece in collaboration with the Hellenic Cooperative Oncology Group (HeCOG). The study was approved by the Bioethics committees of National Center of Scientific Research “Demokritos” (240/EHΔ/11.3 [Number for the Bioethics Committee decision] updated on February 14, 2014) and Papageorgiou Hospital (193rd Decision of Bioethics Committee, January 15,

Results

The present study was performed on 2,449 breast cancer patients, including 2,408 females and 41 males, to determine the frequency of the c.1100delC allele of the CHEK2 gene in the Greek population. The median age of female and male breast cancer diagnosis was 49 years (range: 20−70 years) and 59 years (range: 39−80 years), respectively. A total of 1,383 of 2,408 (57.4%) patients developed breast cancer before the age of 50, whereas 1,020 of 2,408 (42.3%) patients were diagnosed before the age

Discussion

In the present study, we assessed the frequency of the CHEK2 c.1100delC mutation in a cohort of 2,449 Greek breast cancer patients. Four c.1100delC carriers were identified among the female breast cancer cases tested, giving rise to a frequency of 0.16%. This suggests that this mutation is rare, but it is not negligible in Greece. Our findings are supported by the large number of patients tested. This is the first study on the frequency of this specific allele in the Greek population, and it is

Acknowledgments

We thank the patients for their participation in this study. P.A. acknowledges support from the research program ARISTEIA. This research was co-financed by the European Union (European Social Fund, ESF) (ARISTEIA 39, P. BROCA) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)−Research Funding Program of the General Secretariat for Research & Technology (ARISTEIA 39, P. BROCA), which invests in

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