Clinical and Genetic Determinants of Hepatocellular Carcinoma in a Turkish Cohort: Impact of SLCO1B1 and SLCO1B3 Germline Variations and Demographic Risk Factors.

Organic anion-transporting polypeptides (OATPs) are crucial for hepatic uptake. However, the independent contribution of SLCO1B1/1B3 germline variations to hepatocellular carcinoma (HCC) susceptibility remains controversial. This study investigated SLCO1B1/1B3 polymorphisms and HCC risk in a Turkish cohort, accounting for clinical, viral, and metabolic confounders. In this retrospective case-control study (81 HCC patients, 162 healthy controls), fully adjusted multivariable logistic regression models were constructed across multiple inheritance configurations (dominant, recessive, and additive) and adjusted for age, sex, and viral status (HBV/HCV) to address demographic and etiological discrepancies. Genotyping for SLCO1B1 (c.388A>G, c.521T>C) and SLCO1B3 (c.334T>G, c.699G>A) was performed using PCR-RFLP, cross-verified via automated digital capillary electrophoresis. Exploratory univariate analysis showed the SLCO1B1 388A>G variant was more prevalent in the HCC group. However, after strict adjustments for multiplicity and controlling for background viral etiology, age (OR: 1.10) and male sex (OR: 5.82, 95% CI: 2.74-12.41) remained the primary independent predictors, whereas the statistical significance of the genetic variant completely dissolved (p = 0.673). Notably, HCC patients exhibited profound hypocholesterolemia that significantly correlated with liver dysfunction severity; a significant inverse correlation was found between Child-Pugh scores and total cholesterol (r = -0.286, p = 0.031), validating that metabolic decline is a consequence of hepatic synthetic failure rather than an independent risk factor. Ultimately, age, male sex, and background etiological factors are the primary independent determinants characterizing HCC in this cohort, confirming that common germline SLCO variations do not exert a robust independent influence once major demographic and clinical confounders are considered.