Abstract
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.