Irrelevance of CHEK2 variants to diagnosis of breast/ovarian cancer predisposition in Polish cohort

Abstract

CHEK2 gen encodes cell cycle checkpoint kinase 2 that participates in the DNA repair pathway, cell cycle regulation and apoptosis. Mutations in CHEK2 gene may result in kinase inactivation or reduce both catalytic activity and capability of binding other proteins. Some studies indicate that alterations in CHEK2 gene confers increase the risk of breast cancer and some other malignancies, while the results of other studies are inconclusive. Thus the significance of CHEK2 mutations in aetiology of breast cancer is still debatable. The aim of our study was to evaluate the relationship between the breast/ovarian cancer and CHEK2 variants by: i) the analysis of the frequency of selected CHEK2 variants in breast and ovarian cancer patients compared to the controls; ii) evaluation of relationships between the certain CHEK2 variants and clinico-histopathological and pedigree data. The study was performed on 284 breast cancer patients, 113 ovarian cancer patients and 287 healthy women. We revealed the presence of 430T > C, del5395 and IVS2 + 1G > A variants but not 1100delC in individuals from both study and control groups. We did not observe significant differences between cancer patients and controls neither in regard to the frequency nor to the type of CHEK2 variants. We discussed the potential application of CHEK2 variants in the evaluation of breast and ovarian cancer predisposition.

Recurrent Mutations in BRCA1, BRCA2, RAD51C, PALB2 and CHEK2 in Polish Patients with Ovarian Cancer

“…CHEK2 mutations are known to increase the risk of prostate and breast cancer [29,[36][37][38]. With regards to ovarian cancer, the results are inconsistent [21,25,27,37,39]. In our study there was no significant association of tested CHEK2 mutations, including 2 protein truncation and 1 missense mutation, with ovarian cancer risk.…”

A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland

“…Among BC women from throughout Poland and the South-Western Poland, these mutations were detected with higher frequency than in our investigations: 8.6% (385/4.454) and 9.9% (28/284), respectively [7,8]. …”

“…On the contrary, Myszka et al (2011) did not show any relationship between the four investigated CHEK2 mutations and the risk of BC among BC women from the South-Western Poland [8]. Such correlation was not found either by Kwiatkowska et al (2006), who investigated only the 1100delC mutation in women with BC originating from East-Central, West-Central and South-Eastern Poland [9].…”

Population biobanking in selected European countries and proposed model for a Polish national DNA bank

“…The most important hopes connected with the development of biobanks are: a better recognition of genetic and environmental factors of the hereditary diseases, examining people’s susceptibility to specific diseases (Frazier et al 2008; Wang et al 2010; Brozek et al 2011; Myszka et al 2011); more effective personalized preventive care (e.g. the modern spectrometry allows detection of more than 30 metabolic disorders using the neonatal screening blood spot) (Sharrard and Pollitt 2007), adaptation of the treatment to the patient’s individual genetic characteristics by development of pharmacogenetics (personalized medicine) (Roses 2000; Matimba et al 2008; Szczepanek et al 2011) inventing innovative drug therapies and discovering new biomarkers of many diseases with the use of modern sequencing technologies (Pareek et al 2011).…”