Associations between ALDH Genetic Variants, Alcohol Consumption, and the Risk of Nasopharyngeal Carcinoma in an East Asian Population.

Wen-Ling Liao,Wen-Hui Su,Ya-Wen Chang,Kai-Ping Chang,Fu-Chun Chan,Che-Hong Chen,Hen-Hong Chang

doi:10.3390/genes12101547

Abstract

Nasopharyngeal carcinoma (NPC) and alcohol flush syndrome are thought to be strongly influenced by genetic factors and are highly prevalent amongst East Asians. Diminished activity of aldehyde dehydrogenase (ALDH), a major enzyme in the alcohol-metabolizing pathway, causes the flushing syndrome associated with alcoholic consumption. The genetic effect of ALDH isoforms on NPC is unknown. We therefore investigated the association between the genetic polymorphisms of all 19 ALDH isoforms and NPC among 458 patients with NPC and 1672 age- and gender-matched healthy controls in Taiwan. Single-nucleotide polymorphisms (SNPs) located between the 40,000 base pairs upstream and downstream of the 19 ALDH isoform coding regions were collected from two genome-wise association studies conducted in Taiwan and from the Taiwan Biobank. Thirteen SNPs located on ALDH4A1, ALDH18A1, ALDH3B2, ALDH1L2, ALDH1A2, and ALDH2 Glu487Lys (rs671) were associated with NPC susceptibility. Stratification by alcohol status revealed a cumulative risk effect for NPC amongst drinkers and non-drinkers, with odds ratios of 4.89 (95% confidence interval 2.15–11.08) and 3.57 (1.97–6.47), respectively. A synergistic effect was observed between SNPs and alcohol. This study is the first to report associations between genetic variants in 19 ALDH isoforms, their interaction with alcohol consumption and NPC in an East Asian population.

Highlights

Nasopharyngeal carcinoma (NPC) is more common in East and Southeast Asia than in Western countries, with more than 70% of cases worldwide originating from this Asian region
A total of 1245 subjects (249 cases and 996 controls) served as the discovery cohort to search for genetic risk factors associated with NPC, while 840 subjects (164 cases and 676 controls) served as the replication cohort for the identified genetic Single-nucleotide polymorphisms (SNPs) (Figure 1)
To the best of our knowledge, this study is the first to investigate the association between genetic variants in 19 aldehyde dehydrogenase (ALDH) isoform polymorphisms and the risk of NPC in an East Asian population residing in Taiwan

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is more common in East and Southeast Asia than in Western countries, with more than 70% of cases worldwide originating from this Asian region. The remarkable geographical distribution of NPC incidence and family history as a strong risk factor suggests that host genetic susceptibility plays an important role [2,3]. Additional host genetic susceptibility factors have remained elusive. Lifestyle behaviors such as salted fish intake and cigarette smoking significantly increase the risk of NPC in Asian populations [8]. The association between alcohol consumption and NPC risk is inconsistent in many studies [9,10]. Two meta-analyses have indicated that the risk of developing NPC may increase with alcohol consumption; in both meta-analyses, drinking and high-frequency drinking increased the risk of NPC [11,12]

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Results

Discussion

Conclusion