Exploring SLC1A5 (ASCT2), SLC7A5, and SLC3A2 (LAT1) Genetic Variants in Colorectal Cancer: Implications for Prognosis...

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, with up to 20% of patients presenting with metastatic disease at diagnosis. The clinical relevance of amino acid transporters ASCT2 and LAT1 in CRC, particularly Caucasian populations, remains underexplored. This study evaluates the prognostic impact of single nucleotide polymorphisms (SNPs) in the genes encoding these transporters (SLC1A5, SLC7A5, and SLC3A2) in a European population.

A total of 212 patients with CRC were included, with a median follow-up of 89 months. A tagSNP approach was applied to select 28 SNPs, genotyped using MassARRAY^® iPLEX Gold Technology. Kaplan-Meier analysis, log-rank tests, and Cox proportional-hazards models were used to assess the association between SNPs and overall survival (OS). Multivariate models adjusted for clinicopathological covariates.

Five tagSNPs were significantly associated with CRC prognosis. Specifically, SLC1A5 rs1862335 (p=0.040), SLC7A5 rs1060253 (p=0.022), and SLC3A2 rs12804553 (p=0.029) and rs2070870 (p=0.021) significantly affected five-year OS. In multivariate analysis, carriers of the SLC1A5 rs1862553 G allele had increased mortality risk [hazard ration (HR)=1.88, 95% confidence interval (CI)=1.09-3.23, p=0.022), as did carriers of the SLC3A2 rs12804553/rs2070870 T/C alleles (HR=2.22, 95%CI=1.24-3.99, p=0.007). Individuals harboring all three risk alleles had a 2.3-fold increased risk of death (HR=2.27, 95%CI=1.24-4.14, p=0.008).

Genetic variants in ASCT2 and LAT1-related genes are independently associated with survival in CRC, supporting the growing body of evidence supporting personalized medicine and highlighting the need to consider both genetic and tumor heterogeneity when defining risk and tailoring treatment strategies.