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Abstract Background Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)‐related HCC. Methods In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway‐related genes and overall survival (OS) of 866 patients with HBV‐related HCC. Results It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV‐related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose‐response manner (ptrend

Abstract Background Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis‐related genes on survival in hepatitis B virus (HBV)‐related hepatocellular carcinoma (HBV‐HCC) patients remains unknown. Methods We used two‐stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosis‐related genes and overall survival (OS) of 866 HBV‐HCC patients. Results We identified that two potentially functional SNPs (CREB3 rs10814274 C > T and GALNT14 rs17010547 T > C) were significantly independently associated with the OS of HBV‐HCC patients (CT + TT verse CC, hazards ratio (HR) = 0.77, 95% confidence interval (CI) = 0.67–0.89, p

Background: Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis-related genes on survival in hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) patients remains unknown. Methods: We used two-stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosisrelated genes and overall survival (OS) of 866 HBV-HCC patients. Results: We identified that two potentially functional SNPs (CREB3 rs10814274 C>T and GALNT14 rs17010547 T>C) were significantly independently associated with the OS of HBV-HCC patients (CT+TT verse CC, hazards ratio (HR)=0.77, 95% confidence interval (CI)=0.67–0.89, p<0.001 for rs10814274 and TC+CC verse TT, HR=0.66, 95% CI=0.53–0.82, p<0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1–2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR=0.56, 95% CI=0.45– 0.70, p<0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival-associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells. Conclusion: These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV-HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]