Inverse Association between Glucose‒6‒Phosphate Dehydrogenase Deficiency and Hepatocellular Carcinoma

Document Type: Research Articles


1 Dipartimento di Medicina Clinica e Sperimentale, University of Sassari, Sassari 07100, Italy.

2 Baylor College of Medicine, 77030 Houston, Texas, USA.


Background: Studies in experimental models and humans suggest that glucose‒6‒phosphate dehydrogenase
(G6PD) deficiency, an inherited condition, may be inversely related to hepatocellular carcinoma (HCC). We tested
this hypothesis in a large cohort of Sardinian patients. Methods: A case-control study was performed using data
from 11,143 records of patients who underwent upper endoscopy between 2002 and 2017. Gender, age, G6PD status
and information regarding the presence of HCC, were recorded. Cases (HCC positive) and controls (HCC negative)
were compared for the presence of G6PD deficiency adjusting for major HCC risk factors using logistic regression.
Results: Overall, 114 HCC cases and 11,029 controls were identified. G6PD deficiency was detected in 11.5% of
study participants, and was associated with a reduced risk of HCC [odds ratio (OR); 0.451; 95% confidence interval
(CI), 0.207−0.982] after adjusting for all covariates. Factors significantly associated with HCC were cirrhosis (OR,
23.30; 95% CI, 11.48−47.25), diabetes (OR, 2.396; 95% CI, 1.449−3.963), among infection hepatitis HBV with an
OR of 2.326, age ≥65 years (OR, 1.941; 95% CI, 1.234−2.581) and male gender (OR, 1.611; 95% CI, 1.006−3.081).
Conclusions: Our study revealed a significant inverse association between G6PD deficiency and risk of HCC. These
findings need to be confirmed in further studies.


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