The Defective Allele of <i>Aldehyde Dehydrogenase 2</i> Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma

Abstract

<b>Background:</b> The <i>Aldehyde dehydrogenase 2 (ALDH2)</i> mutant genotypes contain an allele encoding defective ALDH2 with reduced efficacy of alcohol metabolism leading to accumulation of highly toxic and carcinogenic acetaldehyde. It can induce unpleasant "Asian flush syndrome" and associate with increased risk of cancers. However, to date, little is known about <i>ALDH2</i> genotypes in relation to the postoperative prognosis of hepatocellular carcinoma (HCC). <b>Methods:</b> From 2002 to 2012, 419 HCC patients receiving surgical resection of HCC were enrolled for <i>ALDH2-</i>rs671 genotyping and outcome correlation. <b>Results:</b> Of the patients included, 202 were <i>ALDH2</i>-rs671 "GG" (wild type) and 217 were mutant (defective) "AA" + "GA" genotype. Kaplan-Meier analysis indicated that "GG" genotype significantly associated with shorter metastasis-free (P = 0.034) and overall (P = 0.005) survival, but not recurrence-free survival (P = 0.281). Univariate followed by multivariate Cox proportional hazard analysis showed that "GG" genotype was an independent clinical predictor for shorter time-to-distant metastasis (adjusted P = 0.019) and shorter overall survival (adjusted P = 0.001). Subgroup analysis showed that in patients with negative hepatitis B surface antigen, Edmonson's histology grade < 3, and aspartate transaminase > alanine transaminase, the <i>ALDH</i>2-rs671-GG genotype was associated with both shorter time-to-metastasis and shorter overall survival. <b>Conclusions:</b> HCC patients carrying a defective allele of <i>ALDH2</i> had a favorable postoperative outcome.