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

Po-Han Huang; Ching-Chih Hu; Cheng-Hung Chien; Li-Wei Chen; Rong-Nan Chien; Yi-Shiuan Lin; Mei Chao; Chih-Lang Lin; Chau-Ting Yeh

doi:10.7150/jca.33221

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

J Cancer. 2019 Oct 3;10(23):5735-5743. doi: 10.7150/jca.33221. eCollection 2019.

Authors

Po-Han Huang^{1

2}, Ching-Chih Hu^{2

3}, Cheng-Hung Chien^{2

3

4}, Li-Wei Chen^{2

3

4}, Rong-Nan Chien^{1

2

3

4}, Yi-Shiuan Lin⁵, Mei Chao^{1

6

7}, Chih-Lang Lin^{1

2

3

4}, Chau-Ting Yeh^{1

2}

Affiliations

¹ Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
² College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
⁴ Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
⁵ Wesley Girls High School, Taipei, Taiwan.
⁶ Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan.
⁷ Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.

Abstract

Background: The Aldehyde dehydrogenase 2 (ALDH2) 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 ALDH2 genotypes in relation to the postoperative prognosis of hepatocellular carcinoma (HCC). Methods: From 2002 to 2012, 419 HCC patients receiving surgical resection of HCC were enrolled for ALDH2-rs671 genotyping and outcome correlation. Results: Of the patients included, 202 were ALDH2-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 ALDH2-rs671-GG genotype was associated with both shorter time-to-metastasis and shorter overall survival. Conclusions: HCC patients carrying a defective allele of ALDH2 had a favorable postoperative outcome.

Keywords: ALDH2 genotype; hepatocellular carcinoma (HCC); overall survival..