Vastagbélrák-hajlamosító DNS-szekvencia-variációk tumormentes és vastagbél-daganatos populációban Magyarországon. Az egyedi daganathajlam becslése
Abstract: Genome-wide association studies (GWAS) using population-based designs have identified many genetic loci, at which common variants can influence the risk of developing the sporadic colon cancers. These are single nucleotide polymorphisms (SNPs) located on different chromosomes, close to genes involved in cancer developing process, and the SNPs modify their functions, and as a consequence the cancer risk is increased. Our aim was to provide frequency distributions data of variable
... a of variable (risk) allele of six independent SNPs in patients with colorectal cancers and in control Hungarian population, predicting the increased risk effect of sequence variant of SNPs. We also investigated the frequency distribution of tumor localization between right or left half of large bowel as well as the RAS mutation status. 47 non-tumorous patients and 47 patients with colorectal cancer were given oral mucosa cells or blood samples for SNP analysis. After DNA isolation, an LC480 (Roche) type PCR instrument, asymmetric LATE PCR method and melting point analysis were used for detection of sequence variations, by the assistance of two SNP specific primers, unlabeled specific probe and intercalating fluorescent dye. Genomic frequency distribution of variable alleles of SNPs predisposed to tumor development have been investigated in colorectal cancer carrier patients and the results have been compared with the same allele frequency distribution data obtained from the non-tumorous control patients and from CEU population stored in SNPnexus data base. The homozygous risk alleles of SNPs showed a 1.5–2.3-time increase in colorectal cancer carrier patients then in control and CEU patients, but the heterozygous risk allele distribution was identical in tumorous and control population. The frequency distribution of homozygous risk alleles of six SNPs was also investigated in the same time and some patients. Among 47 patients with colorectal cancer, in 3 patients carrying 3 SNPs with homozygous risk alleles, in additional 5 tumor samples two and 24 samples contain only one SNP's homozygous risk alleles, and in 15 patients, SNPs with homozygous risk alleles do not occur. In 47 control patients, only 3 samples contain two SNPs with homozygous risk alleles and 17 samples contain only one SNP with homozygous risk alleles. Significant differences of the tumorous and the control population can be seen detected. NRAS mutation was not found. Our results showed a real increased risk effect of several newly recognized low-penetrance colorectal cancer susceptibility genetic variants by influence of the regulation of neighboring genes, however, the degree of cancer risk is individual, and influenced by others environmental factors, such as dietary factors. Orv Hetil. 2018; 159(40): 1614–1623.