Background: Colorectal cancer is a major public health burden in Hungary, with one of the highest incidence and mortality rates in Europe. Long non-coding RNAs (lncRNAs) have emerged as key regulators in tumorigenesis, but population-specific genetic associations remain understudied. This study aimed to investigate whether single-nucleotide polymorphisms (SNPs) in lncRNA genes are associated with colorectal cancer susceptibility, with attention to tumor site- and sex-specific effects. Methods: We conducted an exploratory case–control study involving 91 Hungarian participants (38 patients with colorectal lesions and 53 controls). Genotyping of six SNPs located in HOTAIR, PTCSC3, H19, CCAT1, and CCAT2 was performed using TaqMan-based qPCR. Associations were tested using allele frequency analysis, different genotype models (dominant, recessive, additive), and binary logistic regression, including stratified analyses by tumor subtype and sex. Results: While no significant associations were found in the unadjusted overall case–control comparisons, logistic regression including sex revealed that HOTAIR rs12826786 and rs7958904 were significantly associated with a reduced risk of colorectal lesions, particularly in females (p = 0.022 and p = 0.043). Analyses by tumor localization revealed that H19 rs2839698 and PTCSC3 rs944289 were more frequent in colon than in rectal tumors (p = 0.017 and p = 0.035) and were associated with a reduced risk of rectal tumors (OR = 0.18 and OR = 0.20), suggesting that these variants may influence tumor site rather than overall susceptibility. None of the results remained significant after Bonferroni correction. Conclusions: Our findings suggest that these selected lncRNA-related SNPs may contribute to colorectal cancer risk in a sex- and site-specific manner. These preliminary results warrant further validation in larger, independent cohorts and functional studies.

Background: Gastrointestinal (GI) cancers, particularly colorectal, gastric, and liver cancers, account for a major global burden of incidence and mortality and remain important targets for genetic susceptibility research. Long non-coding RNAs (lncRNAs) can regulate gene expression and are increasingly studied in carcinogenesis. Numerous case–control studies have investigated associations between lncRNA polymorphisms and cancer risk, but findings are inconsistent. This study systematically evaluated the association between lncRNA single nucleotide polymorphisms (SNPs) and GI cancer susceptibility. Methods: A systematic literature search from Embase, Medline, Scopus, and Web of Science databases identified 174 potentially extractable studies. Eligible studies were case–control or cross-sectional studies published up to 8 May 2026; case reports, reviews, and meta-analyses were excluded. After screening for identical cancer type, identical SNP, and sufficient statistical data, only variants supported by at least three independent case–control studies were eligible for meta-analysis. Seven SNPs across six lncRNAs, comprising 23 studies (15,131 cases and 20,969 controls), were selected. Because of the limited number of eligible studies, subgroup analyses could not be performed consistently. Odds ratios (ORs) with 95% confidence intervals (CIs) were assessed under allelic, dominant, and recessive genetic models using fixed- or random-effects models according to heterogeneity. Results: In the primary analyses restricted to homogenous Chinese populations, H19 rs3024270 was significantly associated with hepatocellular carcinoma under allelic (OR = 1.22, 95% CI: 1.05–1.42, p = 0.01) and dominant models (OR = 1.22, 95% CI: 1.03–1.45, p = 0.02). Exploratory analyses including mixed populations identified additional associations, with the strongest observed for MEG3 rs7158663 and colorectal cancer, showing significant risk elevation under allelic (OR = 1.42, 95% CI: 1.25–1.63, p < 0.00001), dominant (OR = 1.42, 95% CI: 1.20–1.68, p < 0.0001), and recessive models (OR = 1.98, 95% CI: 1.46–2.68, p < 0.0001). PRNCR1 rs16901946 showed a significant association with gastric cancer under the dominant model (OR = 1.20, 95% CI: 1.02–1.41, p = 0.03), while GAS5 rs145204276 demonstrated a recessive-model association with gastric cancer (OR = 1.30, 95% CI: 1.16–1.46, p < 0.0001). In contrast, GAS5 rs145204276 in colorectal cancer; H19 rs2839698 and MALAT1 rs619586 in hepatocellular carcinoma yielded heterogeneous or unstable pooled estimates. Findings should be interpreted cautiously due to the limited number of studies, heterogeneity, and potential publication bias. Conclusions: Among the primary analyses, H19 rs3024270 showed the most consistent association with HCC susceptibility. Exploratory analyses identified candidate variants, including MEG3 rs7158663, PRNCR1 rs16901946, and GAS5 rs145204276. Population-specific effects and study heterogeneity remain important limitations. PROSPERO registration number for this study: CRD42023389742.

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.