Exploratory Analysis of VEGF Polymorphisms and Colorectal Cancer Risk in a Hungarian Population: A Case-Control Study

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death in Hungary, with both incidence and mortality rates being among the highest in Europe. Genetic variants that influence inflammation, vascular development, or alcohol metabolism may contribute to CRC susceptibility. This pilot study aimed to investigate, using a candidate gene approach, whether specific polymorphisms in the ALDH2, TNF-α, and VEGF genes are associated with colorectal cancer risk in a Hungarian population.

We conducted a case-control study involving 89 Hungarian participants, including 36 patients with CRC and 53 cancer-free controls. Genotyping of four single nucleotide polymorphisms (rs886205, rs1800629, rs2010963 and rs699947) were performed using TaqMan-based qPCR. Statistical analyses included logistic regression under additive, dominant, and recessive genetic models, adjusted for sex and with sex-stratification. Further exploratory analyses examined genotype distributions by diagnosis subtype.

Two variants in the VEGF gene showed possible associations with CRC. The rs699947 AA genotype under a recessive model showed nominal significance for increased CRC risk (adjusted OR=2.97, 95% CI=1.02-8.69, p=0.047), while the rs2010963 C allele under a dominant model suggested a possible protective effect, particularly in males (unadjusted OR=0.23, 95% CI=0.06-0.95, p=0.041). No associations were observed for ALDH2 rs886205 or TNF-α rs1800629, possibly due to the low representation of certain genotypes. None of the nominally significant associations remained statistically significant after applying the Bonferroni correction.

Although limited by sample size, our findings suggest that two VEGF polymorphisms may act as possible modulators of CRC risk in the Hungarian population, supporting further investigation in larger, independent cohorts.