Perform this test if:
- You want to get to know your genetic predispositions to breast cancer
- There were cases of breast or ovarian cancer in your family, especially if this condition affected your mother or grandmother,
- You consider the use of hormonal contraception or hormonal replacement therapy
- You use hormonal contraception or hormonal replacement therapy
- You have been diagnosed with breast or ovarian cancer
Detection of BRCA1 gene mutations
The test consists in the identification of six mutations in BRCA1 gene: 5382insC, C61G, 185delAG, 4153delA,3819del5, and C64R.
The occurrence of BRCA1 gene mutation indicates a genetic predisposition to breast and ovarian cancer. Breast cancer is the most common cancer affecting women. The risk of getting that type of cancer is 10%. Ovarian cancer is the sixth most common cancer with the risk of 2%. In the majority of Polish patients with breast and/ or ovarian cancer, the following mutations in BRCA1 gene are discovered: 5382insC, C61G. Other recurrent mutations in persons with diagnosed cancer are: 185delAG, 4153delA, 3819del5, and C64R . The frequency of mutation occurrence changes depending on the geographical region of Poland. The product of BRCA1 gene is a protein participating in the process of restoration of damaged DNA, and it plays an important function in the control of cell divisions. Mutations of BRCA1 gene lead to the disruption of cell cycle, the consequence of which is the destabilisation of genome, which may lead to the process of cancerisation. The occurrence of BRCA1 gene mutation increases the risk of breast cancer up to approx. 65% and ovarian cancer up to approx. 39%. Mutations of BRCA1 gene are inherited in an autosomal, dominant manner. Breast and ovarian cancers the basis of which are BRCA1 gene mutations exhibit characteristic clinical features. This applies to average age of condition diagnosing, which is usually premenopausal period in the case of breast cancers. In approximately 18 to 32% of cases, it is characterised by bilateral presence and fast growth rate. The detection of BRCA1 ovarian cancers takes place in the late advancement stage (III°/IV° according to FIGO).
Detection of NOD2 gene mutations
The test consists in the identification of 3020insC mutation in NOD2 gene.
The mutation (3020insC) in NOD2 gene is related to the predisposition to the development of Crohn’s disease and many cancer types, including breast cancer at a young age. The Crohn’s disease is a chronic and non-specific inflammatory condition of intestines. The symptoms of the disease depend on the location, extension and advancement of lesions in gastrointestinal tract, and they can lead to the development of large intestine cancer. The mutation 3020insC consists in the insertion of cytosine nucleotide into 3020 position in exon 11 of NOD2 gene present in chromosome 16. The product of NOD2 gene belongs to proteins participating in immunological response to bacterial infections. The presence of mutation in NOD2 gene is related to increase of risk of breast cancer, large intestine cancer, ovarian cancer, lung cancer and thoracic cancer by approx. 1.5 times.
Detection of CHEK2 gene mutations
The test consists in the detection of two mutations: I157T and IVS2+1G>A in CHEK2 gene.
The mutations in the area of CHEK2 gene cause the increase of predisposition towards a number of cancer types, including: breast cancer, ovarian cancer, prostate cancer, large intestine cancer, kidney cancer, papillary thyroid cancer and family stomach cancer. CHEK2 gene present in chromosome 22 belongs to the group of genes involved in DNA reparation. The product of CHEK2 gene is an antioncogene, the function of which is the prevention of entry with damaged DNA into the cell cycle phase. Mutations in CHEK 2 gene lead to the disruption of antioncogenetic functions of CHEK2 protein, and therefore they might induce cancerisation processes. The most frequent mutations in CHEK2 gene in Polish population are I157T and IVS2+1G>A with the frequency of occurrence of respectively 4.8% and 0.5%. 470T>C [p.I157T] mutation consists in the replacement of nucleotide T with C in exon 3 of CHEK2 gene, which leads to the change of isoleucine amino acid into threonine. The consequence of IVS2+1G >A mutation in the intron 2 of CHEK2 gene is the formation of the incorrect product as a result of erroneous splicing (intron removal). The occurrence of CHEK2 gene mutation increases the risk of breast cancer by approx. 2 to 7 times. Higher risk exists in families with breast cancer in relatives. Mutations in the area of CHEK2 gene are also related to increased risk of prostate, kidney, thyroid and large intestine cancer as well as family stomach cancer, which is approx. twice as high [2,3]. The carriers of mutations in CHEK2 gene also suffer from the doubled risk of breast cancer development in the second breast and also the doubled risk of disease recurrence.