Adverse Histopathological Features in Colorectal Cancer Associated with KRAS rs61764370 SNP: A Preliminary Study

<b>Background/Objectives</b>: The <i>KRAS</i> rs61764370 T>G single-nucleotide polymorphism (SNP), located in a let-7 microRNA binding site within the 3' untranslated region (3'UTR) of the <i>KRAS</i> gene, may modulate tumor aggressiveness by altering post-transcriptional gene regulation. This study evaluated its association with adverse histopathological features in colorectal cancer (CRC). <b>Methods</b>: A preliminary study on 83 CRC patients carrying either the TT (wild-type, n = 64) or TG (heterozygous, n = 19) genotype was analyzed. Clinicopathological variables included patient sex, tumor location, American Joint Committee on Cancer (AJCC) staging system, histological grade, perineural invasion (PNI), and lymphovascular invasion (LVI). A composite "tumor aggressiveness" score was defined based on the presence of Grade 3 differentiation, LVI, and/or PNI. Group comparisons were performed using the Chi-square test or Fisher's exact test, as appropriate. <b>Results</b>: No statistically significant differences were observed in sex (<i>p</i> = 0.689), tumor location (<i>p</i> = 0.781), or stage at diagnosis (<i>p</i> = 0.812). Poorly differentiated tumors (Grade 3) were present in 20.3% of TT patients and absent in TG carriers (<i>p</i> = 0.06), while low-grade tumors (Grade 1) were more prevalent among TG patients (47.4%) compared to TT (29.7%). The composite high-aggressiveness score was lower in TG (36.8%) than in TT (48.4%), while co-occurrence of PNI and LVI was similar in both groups (~26%). <b>Conclusions</b>: Although no significant associations were identified, TG carriers showed a tendency toward lower-grade, less aggressive tumors. Given the limited sample size, these findings should be interpreted with caution, necessitating larger cohorts in order to validate results.