Short tandem repeats on X and Y chromosomes in relation to prostate cancer risks in Saudi male population

Prediction of the susceptible population to any hereditary disease is one of the main tracks of human genetics. Although there were studies related between prostate cancer (PrCa) and family hereditary or Y-chromosome alleles frequencies and other studies related between X-chromosome alleles frequency and PrCa, most of them were inconclusive because of the limited number of biomarkers and/or samples as well as the investigation of sex chromosomes markers separately. Forensic short tandem repeats (STRs) are sometimes best to seek information from lineage markers to aid with specific inheritance scenarios. Therefore, many studies were conducted to establish an association between phenotype and genotype in that disease by Y STR lineages. Lineage markers including Y and X-chromosomes markers can aid kinship analysis. Therefore, in the current study it was hypothesized that the analyses of both X and Y-chromosomes together besides increasing the number of investigated markers to 35 markers (23 in Y-chromosome and 12 in X-chromosome) will give comprehensive linkage information between sex chromosomes and PrCa. Most of the previous studies compare PrCa patients only and healthy controls. Also, they examine the genetic biomarkers on Y-chromosome only. While the current study included PCa and benign prostate hyperplasia (BPH) patients as well as examined the biomarkers on X and Y-chromosomes. Multiple comparisons were done, three of them between (malignant, benign, and malignant plus benign patients), respectively, and healthy controls group. One more comparison was established between benign and malignant patients. This research was carried to fill a gap in research by the identification of a genetic biomarker able to predict men’s susceptibility to malignant or benign disease. To the best of our knowledge, this study is the first to analyze 23 DYS loci in PrCa in a Saudi male population and the first to analyze 12 DXS loci in PrCa patients in a Saudi male population, and worldwide. To perform this study, 248 subjects were recruited, comprising 92 patients and 156 healthy controls. All DNA samples were amplified using PowerPlex® Y23 System and Investigator® Argus X-12 QS. The fragments analysis for alleles of 23 DYS and 12 DXS loci were performed using Genetic Analyzer. In this study, the results emphasize the influence of genetic elements on PrCa and some alleles of DYS391, DYS437, DYS390, DYS458, DYS481, DYS389II, DYS393 and DYS570 loci in Y-chromosome, as well as some alleles of DXS10135, DXS10146, DXS10148, DXS10079, DXS10103, DXS10101, DXS7132, DXS10134, DXS7423, and HPRTB loci in X-chromosome in Saudi male population. These genetic biomarkers have the potential to be used as a screening method for prediction of susceptibility to PrCa in the Saudi men population, especially those who has high value (> 4 ng/mL) in the PSA test. From the comparisons between Y-chromosome haplotypes comprising different alleles of clusters (1, 2, 3a, and 3b) for 23 DYS loci, it is likely that men who belong to the Y-chromosome lineages with certain haplotypes have a higher risk to develop PrCa or BPH, compared with males having other haplotypes. While, males belonging to lineages with [12, 22, 10, 11] haplotype of cluster 3a are more protected against PrCa either benign or malignant. Furthermore, the comparisons between X-chromosome haplotypes comprising different alleles of clusters (X1, X2, X3, X4), and (lowest GD loci) for 12 DXS loci showed that it is likely that men who belong to the X-chromosome lineages with particular haplotypes have a significantly higher risk to develop PrCa or BPH compared with males having other haplotypes. The obvious observation in the results of this study that, microvariant alleles (18.2, and 19.2) and (17.2, and 20.2) of DYS458 locus are overrepresented in the PrCa and PBH group in comparison to none in the control group with high OR results; hence, suggesting that men carrying these microvariant alleles of DYS458 locus are at increased risk to develop PrCa or BPH, respectively. Furthermore, microvariant alleles of some X-chromosome loci are overrepresented in BPH group in comparison to none in the healthy control and non in PrCa groups, hence suggesting that men carrying these microvariant alleles are at increased risk to develop BPH. Only one microvariant allele (31.2) of DXS10101 locus is presented more in PrCa group in comparison to BPH group. Therefore, loci that have significant differences in allele frequencies between patients and healthy controls group could be in linkage disequilibrium with tumor-related genes. Although further studies need to be done to confirm this hypothesis.

Text FPSK(p) 2020 2 - ir.pdf Download (3MB)

Actions (login required)

View Item