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Tumor Discovery SNPs rs9929218 and rs6983267 in Kurdish CRC

Table 6. HWE assessment for rs9929218 and rs6983267 in with a meta-analysis that reported ethnic differences in
CRC cases and controls the effect size of rs9929218 on CRC risk, with inconsistent
findings across diverse populations. 19
SNP Group Observed Expected p‑value
genotype genotype The 8q24 region is known as a “gene desert” but
frequencies frequencies harbors regulatory elements that influence the expression
rs9929218 CRC GG: 231 GG: 228.64 0.0023 of oncogenes such as MYC, a key driver of CRC. The
8
GA: 53 GA: 57.72 rs6983267 SNP has been linked to an increased risk of CRC
AA: 6 AA: 3.64 in multiple populations, particularly in individuals carrying
rs9929218 Control GG: 93 GG: 92.16 0.043 the T allele. 11,20 Functional studies have shown that rs6983267
GA: 6 GA: 7.68 enhances transcription factor binding, leading to increased
AA: 1 AA: 0.16
rs6983267 CRC GG: 213 GG: 208.68 0.011 MYC expression and activation of Wnt signaling, both of
which are critical in colorectal carcinogenesis. In our study,
21
GT: 66 GT: 74.65
TT: 11 TT: 6.68 the T allele was detected in 15.2% of CRC cases compared
rs6983267 Control GG: 89 GG: 88.36 0.048 to 6% of controls (p=0.0009), with the GT genotype
GT: 10 GT: 11.28 showing a higher CRC risk (p=0.0107) in the unadjusted
TT: 1 TT: 0.36 analysis. These findings support previous reports that
22
Notes: Expected genotype frequencies were calculated under HWE rs6983267 may play a role in CRC susceptibility. However,
using allele frequencies derived from observed genotypes; as with rs9929218, logistic regression did not confirm an
p-values were computed using Fisher’s Exact test. independent association (p=0.271), suggesting that its
Abbreviations: CRC: colorectal cancer; HWE: Hardy-Weinberg effect may be modulated by other genetic or environmental
equilibrium; SNP: Single-nucleotide polymorphism.
factors. This aligns with findings from a large genome-
wide association study (GWAS), in which rs6983267 was
Table 7. Logistic regression analysis adjusting for clinical
variables. significantly associated with CRC in unadjusted models but
lost significance after accounting for confounders. 23
Variable β SE p Beyond CRC, the rs9929218 polymorphism has
rs9929218 2.3173 1.783 0.194 been associated with increased susceptibility to other
rs6983267 −4.4398 4.032 0.271 gastrointestinal tumors, including gastric and esophageal
Age −0.4991 0.436 0.253 cancers, particularly in East Asian populations. 24,25
Tumor size 1.283 0.523 0.041 Similarly, rs6983267 has been linked not only to CRC
Gender (male vs. female) 0.785 0.289 0.118 but also to other solid tumors such as gastric, prostate,
and pancreatic cancers. However, GWAS have most
5
Anatomical site (colon vs. rectum) −0.914 0.421 0.089 consistently confirmed its strong association with CRC,
Tumor grade (low vs. high) 1.612 0.749 0.034 suggesting a tumor-type-specific regulatory role. These
26
Tumor stage (T2 and earlier vs. T3 and later) 2.034 0.892 0.041 findings indicate that while these SNPs are not exclusive
Nodal invasion (present vs. absent) −1.211 0.512 0.074 to CRC, their prevalence and functional impact may vary
TNM stages (stages 1 and 2 vs. stages 3 and 4) 1.903 0.973 0.050 across cancer types and populations.
Perineural invasion (present vs. absent) 0.989 0.654 0.087 CRC risk is known to vary across ethnic groups, likely
Vascular invasion (present vs. absent) −0.632 0.419 0.102 due to differences in genetic background, environmental
2
Abbreviations: β: Regression coefficients; SE: Standard errors; exposures, and dietary patterns. The frequency of
SNP: Single-nucleotide polymorphism. rs9929218 and rs6983267 risk alleles in the Kurdish
population appears to be comparable to those reported
increasing the risk of colorectal adenomas and invasive in Middle Eastern populations but differs from European
27
5
carcinoma. Our study identified a higher frequency cohorts. For example, a study in an Iranian cohort found
9
of the A allele in CRC cases (11.3%) compared to the a similar association between rs6983267 and CRC risk,
controls (4%), showing a significant association in the while a meta-analysis in European populations reported
unadjusted analysis (p=0.0025). This aligns with previous a higher prevalence of the T allele (up to 20%) compared
10
research demonstrating a link between rs9929218 and to our findings (15.2%). These variations highlight the
increased CRC risk. However, logistic regression analysis importance of conducting population-specific studies to
12
did not confirm an independent effect, suggesting that better understand CRC genetic epidemiology.
other clinical or genetic factors may contribute to CRC Although our study did not confirm an independent
susceptibility in our population. This finding is consistent effect of rs9929218 or rs6983267 on CRC risk, these SNPs

Volume 4 Issue 2 (2025) 88 doi: 10.36922/TD025110021