Abstract
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.
Highlights
Primary hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death in the world, and the associated morbidity and mortality have continued to rise each year [1]
Our finding shows that the effect of genetic correction could improve prediction efficiency of AFP levels for primary hepatocellular carcinoma risk in the elderly Chinese population
This study suggests that the risk prediction performance of serum AFP level for HCC risk could be improved with the effect of genetic correction in the elderly Chinese population
Summary
Primary hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death in the world, and the associated morbidity and mortality have continued to rise each year [1]. The application of AFP is limited in practice, and it is necessary to find new indicators to aid the development novel predictive approaches It could be more helpful if these indicators can be used to show the difference of individuation. The prediction accuracy of PSA could be improved significantly after genetic correction of serum PSA compared to the raw serum PSA levels [18] It suggests that such variants could provide an individual estimate of tumor marker level. We assume that it could be improved the efficiency of HCC prediction using serum AFP by adjusting with genetic variations
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