• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.131-138
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• 2001

Objectives: Alcohol intake has been reported to be a risk factor of laryngeal cancer. Since the aldehyde dehydrogenase 2 (ALDH2) genotype is a major determinant of personal alcohol drinking habit, there is a possibility that ALDH2 genotype would be a risk factor for laryngeal cancer. N-Acetyltransferase 2 (NAT2) is a detoxifying enzyme and its polymorphism has been reported to be related to the risk of many environmental cancers. However, studies on the associations between these two genotypes and laryngeal cancer risk are scarce. We have assessed the effects of alcohol intake and the genotype of ALDH2 and NAT2 on the risk of laryngeal cancer in Koreans. Materials and Methods: Eighty-four pathologically proven laryngeal cancer patients and 168 age matched controls were included as the study subjects. Information about alcohol intake and smoking habit was collected using a self administered questionnaire. ALDH2 and NAT2 genotypes were analyzed using PCR-RFLP methods. Results: Alcohol intake was significant as a risk factor for laryngeal cancer (OR : 2.58, 95% CI : 1.24, 5.36), especially for supraglottic laryngeal cancer (OR : 3.24, 95% CI : 1.02, 10.31). Personal drinking habit was closely related with personal smoking habit, which was a potent risk factor of laryngeal cancer. In a stratified analysis according to the level of cumulative smoking amount, drinking was significant neither in light smokers (equal or less than 30 pack-years) nor in heavy smoker (over 30 pack-years). The ALDH2 genotype was significantly associated with the risk of laryngeal cancer in a univariate analysis. The statistical significance, however, disappeared after adjusting alcohol intake using a multiple conditional logistic model. The NAT2 genotype was not significant as a risk factor for laryngeal cancer. Conclusion: Alcohol drinking and ALDH2 genotype would have indirect effects on laryngeal cancer by their correlations with cigarette smoking or with alcohol drinking. It is less likely that the NAT2 genotype would be a potent risk factor of laryngeal cancer.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.176-188
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• 1999

Objective : The purpose of this study was to evaluate the effects of alcohol on neurocognitive function, psychomotor performance and subjective response in healthy Korean adults with different ALDH2 genotypes. Method : A total of 24 males, half with active $ALDH2^*1/2^*1$ and the other with inactive $ALDH2^*1/2^*2$, was selected through genotyping using restriction fragment length polymorphism. In a double-blind, placebo-controlled cross-over design, each subject consumed 0.5g/kg dose of alcohol, given as a mixture of 40% vodka and orange juice, and placebo(orange juice) on two separate occasions on an average of weekly intervals. The blood alcohol concentrations(BACs) were measured using a breath analyzer at baseline and at 30, 60 minutes after drinking. P300s were measured at baseline and at 30 minutes after alcohol and placebo intake. Vital signs and psychomotor performance[Critical Flicker Fusion Threshold(CFFT), Choice Reaction Time (CRT), Digit Symbol Substitution(DSS)] were measured at baseline and at 60 minutes after alcohol and placebo intake. Subjective responses were measured at the end of the study. The statistical analysis focused on whether there were any differences between groups with different ALDH2 genotypes. Results : The major results are as follows. 1) BACs in the inactive group were overall equivalent to those in the active group. Only in terms of time, BACs were significantly higher overall at 30 minutes than at 60 minutes after alcohol intake. 2) Pulse rates were significantly increased after alcohol intake compared with placebo, and the increase was greater in the inactive than in the active group. 3) P300 latencies in leads Fz(frontal), Cz(cental) and Pz(parietal) were significantly increased after alcohol intake compared to placebo, and the increase was greater in the inactive than in the active group. P300 amplitudes in leads Cz and Pz were significantly decreased overall after alcohol intake compared to placebo. 4) Compared with placebo, alcohol produced significant effect on the psychomotor performance : impairment in the inactive group, improvement in the active group. 5) Compared with placebo, alcohol significantly induced a negative or an intense effect on the subjective responses in the inactive group, but little negative and even a somewhat positive effect in the active group. Conclusions : These results suggest that ALDH isozyme variance might be an important factor to determine the effects of acute dose of alcohol on the various psychobehavioural functions and also to determine the alcohol use pattern and to predict the future development of alcohol overuse and/or abuse.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.239-245
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• 2001

Objective : Dopamine transporter is member of family of Na/Cl dependent neurotransmitter transporter, 12 transmembrane domain, that has high substrate specificity, affinity. It is related with dopamine reuptake in presynaptic vesicle. DAT has a VNTR in its 3'-untranslated region(UTR). 3'-UTR VNTR polymorphism is related with modification of dopamine transmission. The association between with VNTR polymorphism and neuropsychiatric disorders such as alcohol dependence, and low activity ALDH has been studied, but their relationship is unclear. We study about association of 3'-UTR VNTR of DAT gene and G2319A and alcohol dependence. Method : Group of Korean subjects were studied with alcohol dependence(n=49 male) compared to mentally healthy controls(n=53 male). The peripheral blood sample was acquired, and Polymerase Chain Reaction(PCR) amplification, MspI procedure was done. Result : There was a significant difference between alcohol dependence group and normal control(genotype frequency p<0.05, allele frequency p<0.05) Allele A frequency and genotype(GG, GA) frequency was a significant difference between alcohol dependence group and normal control(p<0.05). Conclusion : Our study showed that genetic polymorphism of DAT1 G2319A had relation with alcohol dependence.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4803-4812
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• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.