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Tumor Discovery SNPs rs9929218 and rs6983267 in Kurdish CRC

Cadherin 1 (CDH1) gene and rs6983267 in the 8q24 region This study aims to assess the prevalence of rs9929218 in
are two such variants that have garnered considerable the CDH1 gene and rs6983267 in the 8q24 region among
attention. 4,5 Kurdish CRC patients. By elucidating the distribution of
The CDH1 gene encodes E-cadherin, a protein essential these SNPs within a specific ethnic group, we aim to fill
for cell-cell adhesion and the maintenance of epithelial the existing research gap and enhance the understanding
integrity. Mutations and polymorphisms in CDH1 have of CRC genetics. Furthermore, our findings may support
been implicated in various cancers, including CRC, the advancement of personalized medicine in oncology,
due to their role in tumor progression, invasion, and leading to improved outcomes for patients across diverse
metastasis. Specifically, rs9929218 has been associated populations.
with an increased risk of colorectal adenomas and cancer. 2. Methods
This variant may influence the expression or function of
E-cadherin, thereby contributing to tumorigenesis. As 2.1. Sample populations
6,7
a biomarker, rs9929218 holds potential for identifying As part of a self-funded project, 290 blood samples
individuals at higher risk for CRC and for informing were collected from CRC patients at Hiwa Hospital in
tailored prevention strategies. 8
Sulaymaniyah to investigate the presence of two SNPs. In
The 8q24 region, often described as a “gene desert,” lacks addition, 100 blood samples were obtained from healthy
protein-coding genes but contains regulatory elements individuals (54 males and 46 females), aged 37 – 79 years
that influence the expression of nearby oncogenes, such (median age: 59). CRC cases were selected based on the
as MYC. The SNP rs6983267, located in this region, has availability of clinicopathological data and the presence
been robustly linked to an elevated risk of several cancers, of at least 50% tumor tissue in the biopsy specimens and
including CRC. Functional studies suggest that the G tumor block. The clinicopathological characteristics of the
9,10
allele of rs6983267 enhances the binding of transcription CRC patients are presented in Table 1.
factors, such as TCF7L2, leading to increased MYC
expression and subsequent tumorigenesis. In addition, 2.2. DNA extraction
11
rs6983267’s role in long-range chromatin interactions DNA was extracted from 0.4 mL of blood collected in
underscores the importance of non-coding regulatory EDTA tubes using the QIAamp DNA Blood Kit (Qiagen,
regions in cancer genetics. The association of this SNP with Germany), following the manufacturer’s protocol. The
CRC highlights the potential for targeting non-coding extracted DNA was eluted in 100 µL of buffer and stored at
elements in future therapeutic interventions. 12 −20°C until further use.
Recent studies highlight the necessity of population- 2.3. Primer design and thermal cycling conditions
specific research to enhance our understanding of the
genetic epidemiology of CRC. 13-16 While polymorphisms For detecting both SNPs in this study, single specific primer
such as rs9929218 and rs6983267 have been extensively (SSP)-polymerase chain reaction (PCR) was employed.
investigated, their prevalence and impact vary across ethnic For each SNP, two forward primers were designed – one
groups, and data remain limited for several populations. specific for the mutant allele and another for the wild-type
15
Most genetic association studies have predominantly allele – along with a common reverse primer. This primer
focused on European and East Asian populations, leaving design strategy was applied to both SNPs. The genomic
16
the genetic landscape of understudied groups, such as the sequences of both SNPs were obtained from the National
1
Kurdish population, largely unexplored. Center for Biotechnology Information . Primer design was
performed using Primer3 software . Primer specificity was
2
The Kurdish population, characterized by its unique evaluated using UCSC in silico PCR and MFEprimer-2.0
4
3
genetic background and potential founder effects, to exclude potential primer-dimer formations. To confirm
presents an opportunity to investigate these associations the results, a subset of samples containing both wild-type
further. Understanding the distribution and role of and mutant alleles was selected for direct, bidirectional
rs9929218 and rs6983267 among Kurdish individuals Sanger sequencing. Additional primer sets were used to
affected by CRC could provide valuable insights into amplify the SNP regions for sequencing. PCR products
the genetic underpinnings of CRC in this population
and contribute to the development of tailored screening 1 http://www.ncbi.nlm.nih.gov/pubmed/
and prevention strategies. Addressing this gap through 2 http://biotools.umassmed.edu/bioapps/primer3_www.cgi
diverse, population-based research is crucial for a more 3 http://genome.ucsc.edu/cgi-bin/hgPcr?command=start
comprehensive understanding of CRC susceptibility and 4 http://biocompute.bmi.ac.cn/CZlab/MFEprimer-2.0/index.
risk stratification. cgi/check_dimer

Volume 4 Issue 2 (2025) 83 doi: 10.36922/TD025110021