Mirosław Andrusiewicz1, Izabela Skibińska2, Emilia Gąsiorowska3, Piotr Białas4, Małgorzata Kotwicka5. 1. Department of Cell Biology, Faculty of Health Sciences, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznan, Poland. Electronic address: andrus@ump.edu.pl. 2. Department of Cell Biology, Faculty of Health Sciences, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznan, Poland. Electronic address: iskibinska@ump.edu.pl. 3. Department of Gynecologic Oncology, Faculty of Medicine I, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland. Electronic address: gasiorowska@ump.edu.pl. 4. Department of Cell Biology, Faculty of Health Sciences, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznan, Poland. Electronic address: pbialas@ump.edu.pl. 5. Department of Cell Biology, Faculty of Health Sciences, Poznan University of Medical Sciences, Rokietnicka 5D, 60-806 Poznan, Poland. Electronic address: mkotwic@ump.edu.pl.
Abstract
PURPOSE: The survival rates for ovarian cancer patients remain very low, often as a result of late diagnosis due to the asymptomatic course of the early stage disease. Based on the important biological contribution of human chorionic gonadotropin to various key processes including; cell cycle control, DNA repair, cellular differentiation and developmental processes, we hypothesized that genetic polymorphisms in the genes promoter could be associated with ovarian cancer risk. Thus, the purpose of the study was to determine whether particular polymorphisms occur in the promoter region of the human chorionic gonadotropin polypeptide 5 encoding gene, and if so, are they associated with ovarian cancer outcome. PATIENTS AND METHODS: We analyzed Central European females diagnosed with ovarian cancer (n=95) and controls (n=76) for the occurrence of at least one of three polymorphisms (rs7260002, rs7246045, rs540432391) and their impact on cancer risk. The fluorescence resonance energy transfer technique was used in order to conduct single nucleotide polymorphisms genotyping. RESULTS: The occurrence of two studied polymorphisms, rs7260002 and rs540432391 present in the 5' upstream region of the chorionic gonadotropin (CG) gene were associated with an increased risk of ovarian cancer. The former polymorphism had a minor impact on cancer risk (P=0.049; OR=1.95; 95% CI=0.97-3.92), while the latter had a much larger impact and may be of great importance in the evaluation of cancer development in the analyzed population (p<0.001; OR 8.5; 95% CI 3.59-20.23). CONCLUSIONS: The fluorescence resonance energy transfer application used in tracking the sequence promoter variations of genes expressed during tumorigenesis may be an important factor in early prediction of ovarian cancer. Taking under consideration the elevated CG expression associated with several different cancer types it seems reasonable to estimate if the analyzed polymorphisms could affect cancer outcome.
PURPOSE: The survival rates for ovarian cancerpatients remain very low, often as a result of late diagnosis due to the asymptomatic course of the early stage disease. Based on the important biological contribution of human chorionic gonadotropin to various key processes including; cell cycle control, DNA repair, cellular differentiation and developmental processes, we hypothesized that genetic polymorphisms in the genes promoter could be associated with ovarian cancer risk. Thus, the purpose of the study was to determine whether particular polymorphisms occur in the promoter region of the human chorionic gonadotropin polypeptide 5 encoding gene, and if so, are they associated with ovarian cancer outcome. PATIENTS AND METHODS: We analyzed Central European females diagnosed with ovarian cancer (n=95) and controls (n=76) for the occurrence of at least one of three polymorphisms (rs7260002, rs7246045, rs540432391) and their impact on cancer risk. The fluorescence resonance energy transfer technique was used in order to conduct single nucleotide polymorphisms genotyping. RESULTS: The occurrence of two studied polymorphisms, rs7260002 and rs540432391 present in the 5' upstream region of the chorionic gonadotropin (CG) gene were associated with an increased risk of ovarian cancer. The former polymorphism had a minor impact on cancer risk (P=0.049; OR=1.95; 95% CI=0.97-3.92), while the latter had a much larger impact and may be of great importance in the evaluation of cancer development in the analyzed population (p<0.001; OR 8.5; 95% CI 3.59-20.23). CONCLUSIONS: The fluorescence resonance energy transfer application used in tracking the sequence promoter variations of genes expressed during tumorigenesis may be an important factor in early prediction of ovarian cancer. Taking under consideration the elevated CG expression associated with several different cancer types it seems reasonable to estimate if the analyzed polymorphisms could affect cancer outcome.
Keywords:
DNA sequence changes; FRET – fluorescence resonance energy transfer; Genotype; Human chorionic gonadotropin; Ovarian cancer; Single nucleotide polymorphism