The impact of genes other than BRCA1/2 on brast/ovarian cancers in affected families

Breast cancer is the most common malignancy in Turkey and worldwide. Breast cancer is a complex and multifactorial disease. Approximately 5%-10% of breast cancers are hereditary. Almost 15%-20% of the hereditary breast cancer is attributed to BRCA1/2, mutations. In Turkish population BRCA1/2 mutations compose less than 10% of the hereditary breast cancer. For this reason studying the role of breast cancer susceptibility genes, in additon to BRCA1/2 is necessary. Among different breast cancer susceptibility genes P53, PTEN and CHEK2 are more stressed. Many studies have demonstrated that mutations in these genes are related to the breast cancer and influence therapy outcomes, in some cases. In this study, 12 non- BRCA1/2 Turkish patients whose pedigrees are strong and suggestive were chosen. Genomic DNA samples were isolated from peripheral blood. In P53 and PTEN genes, exons containing mutation hotspots amplified by PCR, exons 2, 3, 5, 6, 7 and 8 in PTEN gene and exons 4, 5, 6, 7, 8 and 9 in P53 gene. In the case of CHEK2 gene whole coding exons (1-14) were amplified by PCR. All amplified exons were sequenced by capillary gel electrophoresis and screened for any possible mutation. As a result all of the 12 patients harbor a c.215C>G (p.Pro72Arg) polymorphism as homozygot in their P53 gene. In 1 out of 12 patient a c.638G>A (p.Arg213Gln) mutation as heterozygot in exon 6 of its P53 gene was detected. All patients carry a c.802-4_802- 3delTT deletion as heterozygot in their PTEN gene.In 1 out of the 12 patients c.470T>C (p.I157T) heterozygot mutation in the CHEK2 gene was found. In conculusion, in Turkish population P53 gene c.215C>G (p.Pro72Arg) and c.638G>A (p.Arg213Gln), PTEN gene c.802-4_802-3delTT and CHEK2 gene c.470T>C (p.I157T) changes may take part in increasing breast cancer risk. But specifying their frequency, their amount of influence on breast cancer in Turkish population and on therapy need more studies. Keywords: Breast cancer, P53 Gene, PTEN Gene, CHEK2 Gene, PCR, DNA Sequencing, Mutation.