Genetic correction of serum AFP level improves risk prediction of primary hepatocellular carcinoma in the Dongfeng-Tongji cohort study.

Serum alpha-fetoprotein (AFP) is the most commonly used tumor biomarker for screening and diagnosis of primary hepatocellular carcinoma (HCC). However, the predictive effect for HCC risk is still unsatisfactory. The aim of this prospective study was to estimate whether the individual genetic correction could improve the prediction efficiency of AFP for HCC risk. A prospective analysis with 9819 baseline HCC-free individuals based on a large population-based Chinese cohort study was performed. Two single-nucleotide polymorphisms (SNPs) associated with serum AFP level were used to calculate the genetic corrected AFP level (rs12506899 and rs2251844). Statistical analysis including logistic regression analysis and the area under the receiver operating characteristic (ROC) curve were used to assess the discriminative ability of the original and genetic corrected AFP level for HCC risk. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were presented. Fifty-seven participants were diagnosed with HCC for the first time. After adjusting AFP level with genetic effects, the participants for HCC risk increased compared to those with AFP level alone (OR = 5.34, 95% CI = 2.57-11.13; P < 0.001 vs. OR = 5.04, 95% CI = 2.46-10.30; P < 0.001). In addition, the area under the curve (AUC) for the discrimination of HCC elevated from 0.611 to 0.726. The efficiency in HCC prediction using serum AFP level can be improved by adjusting AFP level based on genetic effects. The genetic correction effect on serum AFP should be considered in the clinic application of such tumor biomarkers.