Číslo abstraktu: p02
Autoři: Mgr. Radek Měch; Mgr. Irena Urbanovská; Mgr. Jarmila Šimová; RNDr. Magdalena Uvírová; RNDr. David Konvalinka; Mgr. Barbora Kubová; Bc. Andrea Hopenštoková; laborantka Jana Mazurová; Dis. Iveta Žebrákova; MUDr. Renata Kalábová; Bc. Leszek Trombik; Mgr. Jana Žmolíková; Mgr. Oldřich Motyka, Ph.D.; MUDr. Pavel Svoboda, Ph.D.; prof. MUDr. Petr Dítě, DrSc.; Doc.MUDr. Jana Dvořáčková, Ph.D., M.I.A.C
Barrett‘s Esophagus (BE) is a common pre-malignant lesion that predisposes to esophageal adenocarcinoma (EAC). In present days understanding of the molecular mechanisms underlying the development of BE/EAC is crucial. The aim of this work is to analyze these potentially selected mutations/ SNPs and epigenetic changes in candidate genes.
The presence of selected mutations in candidate MSR1, ASCC1 and CTHRC1 genes and one selected SNP in IL18RAP gene was analyzed peripheral blood of 81 patients with suspicion of BE. Two control groups with 132 and 89 samples (MSR1, ASCC1, CTHRC1 and IL18RAP, respectively) were assembled. The methylation statuses of CDKN2A and APC genes were analyzed by qPCR and MS-PCR in 39 biopsy specimens.
Results and conclusions
The germline mutation c.877C>T (p. R293X) in MSR1 gene was detected in 3,70 % (3/81) of patients suspected to BE and in 0,76 % (1/132) of controls, but no significant association between MSR1 gene mutation and presence of BE was found (p=0.0828). In the control group, the mutation frequency correlates with Global Minor Allele Frequency presented by NCBI database (GMAF=0,0078). The frequency of rs917997C allele in IL18RAP gene was close to significant difference in group of BE patients and in control group (freq = 74,39 % case vs. 78,1 % control, p=0.07437). Fisher‘s exact test was applied since the chi squared approximation might have been inaccurate due to the small expected values. Although the significance level below 0.05 was not reached, the obtained p = 0.07437 indicates that the distinction could have been deemed significant if the number of patients in the dataset was higher. In other analyzed genes (ASCC1 and CTHRC1) mutations were not detected. On the contrary, promoter methylation statuses of CDKN2A and APC genes were detected in 28,21 % (11/39) and 92,31 % (36/39), respectively and correlate with published data, which suggest association with intestinal metaplasia, Barrett´s dysplasia and progression to EAC. Searching for and discovering of predisposition genes may improve premorbid risk assessment, genetic counseling, and management.
Datum přednesení příspěvku: 2. 12. 2015