Repurposing non‑invasive prenatal testing data: Population study of single nucleotide variants associated with colorectal cancer and Lynch syndrome

Abstract

In our previous work, genomic data generated through non-invasive prenatal testing (NIPT) based on low-coverage massively parallel whole-genome sequencing of total plasma DNA of pregnant women in Slovakia was described as a valuable source of population specific data. In the present study, these data were used to determine the population allele frequency of common risk variants located in genes associated with colorectal cancer (CRC) and Lynch syndrome (LS). Allele frequencies of identified variants were compared with six world populations to detect significant differences between populations. Finally, variants were interpreted, functional consequences were searched for and clinical significance of variants was investigated using publicly available databases. Although the present study did not identify any pathogenic variants associated with CRC or LS in the Slovak population using NIPT data, significant differences were observed in the allelic frequency of risk CRC variants previously reported in genome-wide association studies and common variants located in genes associated with LS. As Slovakia is one of the leading countries with the highest incidence of CRC among male patients in the world, there is a need for studies dedicated to investigating the cause of such a high incidence of CRC in Slovakia. The present study also assumed that extensive cross-country data aggregation of NIPT results would represent an unprecedented source of information concerning human genome variation in cancer research.

Evaluation and limitations of different approaches among COVID-19 fatal cases using whole-exome sequencing data

“…We investigated the frequencies of these variants and evaluated their possible role using a cohort of 27 Slovak patients who have died of COVID-19. In our previous studies, we described the re-use of the data from NIPT for genome-scale population-specific frequency determination of small DNA variants [ 45 ], copy number variants (CNVs) [ 46 ], and variants associated with colorectal cancer and Lynch syndrome [ 47 ]. Therefore, we assumed that the NIPT data can be utilized as a control group in this population study of COVID-19.…”

Evaluation and Limitations of Different Approaches Among COVID-19 Fatal Cases Using Whole-exome Sequencing Data

“…We investigated the frequencies of these variants and evaluated their possible role using a cohort of 27 Slovak patients who have died of COVID-19. In our previous studies, we described the re-use of the data from NIPT for genome-scale population-speci c frequency determination of small DNA variants [45], CNVs [46], and variants associated with colorectal cancer and Lynch syndrome [47]. Therefore, we assumed that NIPT data can be utilized as a control group in this population study of COVID-19.…”

Determination of the Prevalence of Microsatellite Instability, BRAF and KRAS/NRAS Mutation Status in Patients with Colorectal Cancer in Slovakia

“…[ 3 ] Moreover, local researchers aimed to repurpose local prenatal screening data to identify genetic variants associated with colorectal cancer, focusing on genes associated with Lynch syndrome as the most common germline mutations associated with the development of CRC. [ 4 ] A recently published joinpoint analysis of local CRC trends showed only slight improvement in reduced mortality (0.9%) in the follow-up period from 2001 to 2018 compared to the previous period from 1971 to 2001, limited to the age group from 29 to 45 years old [ 5 ]. Due to the lack of improvement in CRC prevalence, the identification of possible driver mechanisms can help to elucidate the high incidence as well as mortality of CRC in Slovakia, as the underlying cause of this problem is still unclear, with a limited number of regional studies being conducted [ 4 ].…”

“…[4] A recently published joinpoint analysis of local CRC trends showed only slight improvement in reduced mortality (0.9%) in the follow-up period from 2001 to 2018 compared to the previous period from 1971 to 2001, limited to the age group from 29 to 45 years old [5]. Due to the lack of improvement in CRC prevalence, the identification of possible driver mechanisms can help to elucidate the high incidence as well as mortality of CRC in Slovakia, as the underlying cause of this problem is still unclear, with a limited number of regional studies being conducted [4].…”