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PubMed2005

Bioelectronic sniffers for ethanol and acetaldehyde in breath air after drinking.

Two kinds of bioelectronic gas sensors (bio-sniffer) incorporating alcohol oxidase (AOD) and aldehyde dehydrogenase (ALDH) were developed for the convenient analysis of ethanol and acetaldehyde in expired gas, respectively. The sniffer devices for gaseous ethanol and acetaldehyde were constructed by immobilizing enzyme on electrodes covered with filter paper and hydrophilic PTFE membrane, respectively. The AOD and ALDH sniffers were used in the gas phase to measure ethanol vapor from 1.0 to 500 ppm, and acetaldehyde from 0.11 to 10 ppm covering the concentration range encountered in breath after alcohol consumption. Both bio-sniffers displayed good gas selectivity which was attributed to the substrate specificity of the relevant enzymes (AOD and ALDH) as gas recognition material. From the results of physiological application, the bio-sniffers could monitor the concentration changes in breath ethanol and acetaldehyde after drinking. The ethanol and acetaldehyde concentrations in expired air from ALDH2 [-] (aldehyde dehydrogenase type 2 negative) subjects were higher than that of the ALDH2 [+] (positive) subjects. The results indicated that the lower activity of ALDH2 induced an adverse effect on ethanol metabolism, leading to ethanol and acetaldehyde remaining in the human body, even human expired air.

Acetaldehyde↗
PubMed2006

p53 Protein accumulation, cancer multiplicity, and aldehyde dehydrogenase-2 genotype in Japanese alcoholic men with early esophageal squamous cell carcinoma.

Synchronous multiple intra-esophageal squamous cell carcinomas (SCCs) or oropharyngolaryngeal SCCs are common in alcoholics with esophageal SCC, and more frequently found in those with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2). p53 alterations have been suspected as key molecular events in such multifocal esophageal carcinogenesis. We studied 95 Japanese alcoholic men with Tis and mucosal invasive esophageal SCC and found very high levels of p53 protein accumulation occurring in early esophageal SCC. Synchronous cancer multiplicity in the upper aerodigestive tract was found in 40 patients. p53 expression was not correlated with either cancer multiplicity or ALDH2 genotype. The risk for cancer multiplicity was associated with inactive heterozygous ALDH2 alone (OR=4.22) among the risk factors investigated, which also included smoking, less-active alcohol dehydrogenase-1B, and macrocytosis, enhancing the validity of the link between acetaldehyde exposure and cancer multiplicity.

Alcoholism↗
PubMed1997

Alcohol dehydrogenase and aldehyde dehydrogenase genotypes and alcoholism among Taiwanese aborigines.

Previous population association studies have indicated that certain alleles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes may reduce the risk of alcoholism in Oriental populations. In this report we determined the genotypes for three genes, ADH2, ADH3, and ALDH2 among subjects with alcohol dependence (n = 159) and ethnically matched normal controls (n = 149) for the four largest aboriginal groups (Atayal, Ami, Bunun, and Paiwan) in Taiwan. The ethnicity matching used in this study was feasible because there are still few intergroup marriages between these aboriginal groups. On a group level, the rare frequencies of ALDH2*2, the inactive allele of ALDH2, among these aborigines may account partially for their vulnerability to alcohol use disorders. On an individual level, however, the genotypes controlling alcohol metabolism did not account for intragroup differences in vulnerability to alcoholism except in the case of ADH2 for the Ami ethnic group.

Adult↗
PubMed2001

Corneal and stomach expression of aldehyde dehydrogenases: from fish to mammals.

We have studied the distribution of the ALDH3A1, ALDH1A1 and ALDH2 proteins in the cornea and stomach of several animal species, including mammals (C57BL/6J and SWR/J mice, rat and pig), birds (chicken and turkey), amphibians (frog) and fish (trout and zebrafish). High ALDH3A1 protein levels and catalytic activities were detected in C57BL/6J mouse, rat and pig. We found complete absence of the ALDH3A1 protein in SWR/J mice, which carry the Aldh3a1(c) allele characterized by four amino acid substitutions (G88R, I154N, H305R and I352V) and lack of enzymatic activity. This indicates that the SWR/J mouse strain is a natural gene knockout model for ALDH3A1. Traces of ALDH3A1 were detected in rabbit, whereas expression was absent from chicken, turkey, frog, trout, and zebrafish. Interestingly, significant levels of the cytosolic ALDH1A1 and mitochondrial ALDH2 proteins were detected by immunoblot analysis in all examined species that are deficient in ALDH3A1 expression. In contrast, no ALDH1A1 or ALDH2 protein was detected in the species expressing ALDH3A1. It can, therefore, be concluded that corneal expression of ALDH3A1 or ALDH1A1/ALDH2 occurs in a taxon-specific manner, supporting the protective role of these ALDHs in cornea against the UV-induced oxidative damage.

Aldehyde Dehydrogenase↗
PubMed1998

Binding and activation of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is expressed in a tissue-specific fashion with high levels in liver, heart, kidney, and muscle, and low levels in most other tissues. The ALDH2 promoter was found to bind nuclear proteins at a pair of adjacent sites approximately 300 bp upstream from the translation start site, each of which was contacted at motifs containing the hexamer A/GGGTCA. The 3' site was shown to bind in vitro translated HNF-4. It was also shown by electrophoretic mobility shift assay utilizing antibodies against nuclear factors and rat liver nuclear extracts to be bound by hepatocyte nuclear factor 4 (HNF-4), chicken ovalbumin upstream promoter transcription factor I and II, and retinoid X receptors. A reporter construct containing four copies of this promoter element was activated by co-transfection of an HNF-4 expression plasmid in COS-1 and hepatoma cell lines. These results suggest that the tissue specificity of ALDH2 expression is in part determined by its activation by HNF-4.

Aldehyde Dehydrogenase↗
PubMed2000

Genetic and environmental interaction in Japanese type 2 diabetics.

In Japanese type 2 diabetes, which occupies more than 95%, it is an increasingly important problem as a life-style related disease. The total diabetic population is estimated as approximately 7 million with a prevalence of approximately 6%. Along with genetically low postprandial insulin secretion, they are found to be less tolerable to being overweight to develop insulin resistance. The body weight change in the prediabetic era consisting of 508 male patients treated on their diet alone was reviewed and it was found that a few kilograms of weight gain could be a cause of insulin resistance. Moreover, inactive aldehyde dehydrogenese 2 (ALDH2), which is common in Japanese, is found to be a factor in the development of hyperglycemia. In 163 diabetics, HbAlc of the inactive ALDH2 group was 8.1+/-1.3, while that of active ALDH2 was 7.5+/-0.9% (P<0.05) in a light, social drinking group. However, Japanese type 2 diabetes is also changing. In recent years, the data from a 75-g oral glucose tolerance test of 2121 clients showed that insulinogenic index of clients with impaired glucose tolerance was similar to that of a normal glucose tolerance group and that the area under the insulin curve (AUC) was high in younger diabetics. From a life-style modification perspective, the importance of body weight control by diet and exercise as well as refraining from excessive drinking should be emphasized.

Adult↗
PubMed2003

Effects of aldehyde dehydrogenase genotypes on carotid atherosclerosis.

Atherosclerotic diseases are thought to be less frequent in Asians compared with Caucasians. Unlike Caucasians, nearly half of Asians have a functional deficiency in the low Km aldehyde dehydrogenase (ALDH2), a key enzyme in alcohol metabolism, which potentially modifies the prevalence of atherosclerosis. This study examined the associations between ALDH2 genotypes ("typical homo," "hetero" or "atypical homo") and carotid atherosclerosis in 304 Japanese patients. As a measure of carotid atherosclerosis, plaque score (PS) was evaluated by B-mode ultrasonography. Age- and sex-adjusted PS was lower in "atypical homo" genotype patients (2.7 +/- 1.2 [mean +/- standard error], n=21) (p<0.05) and tended to be lower in "hetero" patients (4.5 +/- 0.5, n=116) (p=0.07) compared with "typical homo" patients (5.7 +/- 0.4, n=167). When we controlled for traditional cardiovascular risk factors and alcohol intake, the "atypical homo" genotype was found to be associated with lower PS (beta=-0.13, p<0.05). Based on these findings, the ALDH2 genotypes seem to be associated with the severity of carotid atherosclerosis, potentially modifying the prevalence of atherosclerosis in Asians.

Aged↗
PubMed1999

Blood and urinary levels of ethanol, acetaldehyde, and C4 compounds such as diacetyl, acetoin, and 2,3-butanediol in normal male students after ethanol ingestion.

Aldehyde dehydrogenase (ALDH) isozyme 2 genes were determined in 15 students. Of these subjects, five healthy male students were administered 0.4 kg/kg ethanol. One subject was defective in aldehyde dehydrogenase 2 (ALDH2), two had normal ALDH2, and the other two were hetero type. After the intake of alcohol, the concentration of ethanol, acetaldehyde, and C4 compounds in blood and urine were determined. The student with the inactive form of ALDH2 was flushed and his levels of 2,3-butanediol and acetaldehyde in blood and urine were found to be the highest.

Acetaldehyde↗
PubMed1998

Sheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases.

BACKGROUND: . Enzymes of the aldehyde dehydrogenase family are required for the clearance of potentially toxic aldehydes, and are essential for the production of key metabolic regulators. The cytosolic, or class 1, aldehyde dehydrogenase (ALDH1) of higher vertebrates has an enhanced specificity for all-trans retinal, oxidising it to the powerful differentiation factor all-trans retinoic acid. Thus, ALDH1 is very likely to have a key role in vertebrate development. RESULTS: . The three-dimensional structure of sheep ALDH1 has been determined by X-ray crystallography to 2.35 A resolution. The overall tertiary and quaternary structures are very similar to those of bovine mitochondrial ALDH (ALDH2), but there are important differences in the entrance tunnel for the substrate. In the ALDH1 structure, the sidechain of the general base Glu268 is disordered and the NAD+ cofactor binds in two distinct modes. CONCLUSIONS: . The submicromolar Km of ALDH1 for all-trans retinal, and its 600-fold enhanced affinity for retinal compared to acetaldehyde, are explained by the size and shape of the substrate entrance tunnel in ALDH1. All-trans retinal fits into the active-site pocket of ALDH1, but not into the pocket of ALDH2. Two helices and one surface loop that line the tunnel are likely to have a key role in defining substrate specificity in the wider ALDH family. The relative sizes of the tunnels also suggest why the bulky alcohol aversive drug disulfiram reacts more rapidly with ALDH1 than ALDH2. The disorder of Glu268 and the observation that NAD+ binds in two distinct modes indicate that flexibility is a key facet of the enzyme reaction mechanism.

Aldehyde Dehydrogenase↗
PubMed2005

Differential effects of Mg2+ ions on the individual kinetic steps of human cytosolic and mitochondrial aldehyde dehydrogenases.

Although the structures of mammalian cytosolic and mitochondrial ALDH have been determined, several differences, mainly functional, between these two 70% identical isozymes remain unexplained. A major difference is the differential effect of Mg(2+) ions that inhibits the cytosolic and activates the mitochondrial isozyme. Here, we have investigated the effect of Mg(2+) ions on each individual kinetic step of ALDH1 and ALDH2. The metal ions were found not to affect either acylation or hydride transfer for either isozyme. The lack of a Mg(2+) ion effect on hydride transfer was further demonstrated with an E399Q mutant of ALDH1 whose rate-limiting step had been changed from NADH dissociation to hydride transfer. The other steps, however, were affected by Mg(2+) ions for both isozymes. The metal ions inhibited NADH dissociation, the rate-limiting step for ALDH1, and enhanced deacylation, the rate-limiting step for ALDH2. Our results indicated that, with both isozymes, Mg(2+) ions tightened the binding of NADH, and by binding to the coenzyme, they increased the nucleophilicity of the nucleophile Cys302. The inhibition of ALDH1 and activation of ALDH2 at pH 7.4 are due to their different rate-limiting steps. Mg(2+) ions affected similarly the NADH activation of the esterase reaction for both isozymes. In contrast, the metal ions affected only the NAD(+) activation of ALDH1. This latter finding and other features described here can be rationalized on the basis of the known three-dimensional structures of the isozymes.

Acetaldehyde↗
PubMed2000

Phenobarbital induction of aldehyde dehydrogenase type 2 mRNA in mouse liver: a candidate region on chromosome 7 for a putative regulatory gene.

Phenobarbital (PB) strongly induces in the liver the expression of many genes encoding detoxication enzymes, such as the aldehyde dehydrogenase type 2 in the mouse (Aldh2). With the aim of identifying genes involved in this response, we have undertaken an approach based on a genetic analysis in mice. In a previous report, the genetic analysis of both the C57BL/6J (B6) x DBA/2J (D2) F1 and the (F1 x F1) F2 led us to the hypothesis that Aldh2 responsiveness to PB was under the control of one major locus independent of the structural gene. In the present study, the genetic analysis of the inducibility by PB of Aldh2 in the backcross population B6D2F1 x D2 has allowed us to confirm the involvement of a major regulatory gene in this mechanism. By searching for genetic linkage between this locus and a series of microsatellites DNA markers, we obtained indicative evidence for a region on chromosome 7, which may carry this gene.

Aldehyde Dehydrogenase↗
PubMed2003

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes and male alcohol use disorders in Khon Kaen, north-east Thailand.

A case-control study on the relationship between alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2) and male probable alcohol use disorders (AUD) was performed in Khon Kaen, north-east Thailand. One hundred and fifty-three paired cases (probable AUD) and controls (non-probable AUD) were sampled from villagers aged 18-65 years using the modified Michigan Alcoholism Screening Test - Thai version, controls being matched for gender, age (+/- 4 years) and village. All of the cases and 86.9% of the controls were current drinkers. The percentage of ADH2*1/1 among cases was 47.1%, being significantly larger than the 29.4% among controls, and yielding a univariate odds ratio (OR) of 2.421* (95% confidence interval (CI) = 1.419-4.132) for developing probable AUD. The ALDH2*1/1 proportion among cases, 92.8%, was comparable to the 92.2% among controls, yielding a univariate OR of 1.100 (95%CI = 0.757-1.599). Multivariate analysis based on a conditional logistic regression model and a hierarchically well-formulated model strategy revealed that: (i) the OR of developing probable AUD due to 1 g increment of daily ethanol drinking was 1.110* among farmers (95%CI = 1.054-1.170); (ii) OR due to 1 g increment of daily ethanol drinking was 1.329* among non-farmers (95%CI = 1.109-1.593); (iii) OR due to either ADH2*1/1 or ALDH2*1/1 was insignificant; and (iv) the daily amount of smoking is independently associated with probable AUD. The present findings suggest that one of the genetic factors that may be related to probable AUD among Thai males living in the north-east is the ADH2 gene.

Adult↗
PubMed2003

Oxidation of 4-hydroxy-2-nonenal by succinic semialdehyde dehydrogenase (ALDH5A).

Elevated levels of 4-hydroxy-trans-2-nonenal (HNE) are implicated in the pathogenesis of numerous neurodegenerative disorders. Although well-characterized in the periphery, the mechanisms of detoxification of HNE in the CNS are unclear. HNE is oxidized to a non-toxic metabolite in the rat cerebral cortex by mitochondrial aldehyde dehydrogenases (ALDHs). Two possible ALDH enzymes which might oxidize HNE in CNS mitochondria are ALDH2 and succinic semialdehyde dehydrogenase (SSADH/ALDH5A). It was previously established that hepatic ALDH2 can oxidize HNE. In this work, we tested the hypothesis that SSADH oxidizes HNE. SSADH is critical in the detoxification of the GABA metabolite, succinic semialdehyde (SSA). Recombinant rat SSADH oxidized HNE and other alpha,beta-unsaturated aldehydes. Inhibition and competition studies in rat brain mitochondria showed that SSADH was the predominant oxidizing enzyme for HNE but only contributed a portion of the total oxidizing activity in liver mitochondria. In vivo administration of diethyldithiocarbamate (DEDC) effectively inhibited (86%) ALDH2 activity but not HNE oxidation in liver mitochondria. The data suggest that a relationship between the detoxification of SSA and the neurotoxic aldehyde HNE exists in the CNS. Furthermore, these studies show that multiple hepatic aldehyde dehydrogenases are able to oxidize HNE.

Aldehyde Dehydrogenase↗
PubMed2004

Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review.

Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field.

Alcohol Dehydrogenase↗
PubMed2005

Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region.

While multiple squamous cell carcinomas are often observed in the esophagus and the head and neck region and confound us about the favorable treatments, the reason why some patients are more likely to develop multiple cancers remains obscure. We statistically analyzed clinical factors in 203 patients with newly diagnosed squamous cell carcinoma, to assess the risk of multiple cancers for the establishment of an effective prevention and screening programs. Widespread epithelial oncogenic alterations were assessed as multiple lugol-voiding lesions (multiple LVL) using lugol chromoendoscopy. Genetic polymorphisms of alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2) were identified by PCR-restriction fragment length polymorphism analysis. Forty patients had synchronous multiple cancers and the remaining 163 had solitary cancer. Presence of multiple LVL was the only independent risk factor for multiple cancers [relative risk (RR) = 67; 95%CI, 15-310]. Multiple LVL was observed in only smoking drinkers. Among them, a multivariate analysis demonstrated that the ALDH2 deficiency allele (RR = 5.7; 95%CI, 2.8-11.6) and the slow metabolizing ADH3 allele (RR = 1.9; 95%CI, 1.1-7.9) were the independent risk factors for multiple LVL. Combination of these alleles lead to increase the risk of multiple LVL. In conclusion, an episode of multiple LVL is a remarkable high risk for multiple cancers both at the esophagus and the head and neck region. The interaction between drinking and the ALDH2 deficiency allele increases the risk. In addition, the slow metabolizing ADH3 allele enhances the risk. Prohibiting the use of alcohol and early detection of cancer are strongly recommended for such individuals.

Alcohol Dehydrogenase↗
PubMed2002

The genetics of alcoholism in Polynesians: alcohol and aldehyde dehydrogenase genotypes in young men.

BACKGROUND: The last 10 years have seen growing recognition of the significance of the genes encoding enzymes responsible for hepatic alcohol metabolism as protective factors in the development of alcoholism. METHODS: We have developed DNA sequencing assays for measuring genetic variation at the alcohol dehydrogenase 2 (ADH2), ADH3, and aldehyde dehydrogenase 2 (ALDH2) loci. These have been used to survey volunteer control subjects from three New Zealand ethnic groups (white, Asian, and Polynesian) and young male alcoholics recruited from white and New Zealand Maori patients in a local treatment program. RESULTS: The allele frequency values for whites and Asians obtained in our study closely match those obtained previously in other laboratories. Our data (the first for Polynesians) are 0.42 for ADH2*2, 0.78 for ADH3*1, and 0.00 for ALDH2*2. In the New Zealand Maori alcoholic patients, the ADH2*2 frequency is significantly lower (0.15; p < 0.01). The frequency of ADH3*1 is also lower in this group (0.60), but this value is not significant (0.05 < p < 0.06). CONCLUSIONS: In young male New Zealand Maori, the ADH2*2 allele is a protective factor against alcoholism even in the absence of ALDH2*2.

Alcohol Dehydrogenase↗
PubMed2002

Tandem repeat polymorphism of the CYP2E1 gene: an association study with esophageal cancer and lung cancer.

BACKGROUND: Cytochrome P-450 (CYP) enzymes have been shown to play important roles in chemical carcinogenesis. Reports have indicated that polymorphism in CYP1A1, CYP1A2, CYP2A6, CYP2E1, and CYP2D6 are associated with an altered risk of developing cancers of the lung, bladder, liver, and colon. CYP2E1 plays an important role in alcohol metabolism and participates in the metabolic activation of various carcinogens, such as N-nitrosodimethylamine. Recently, we found repeated sequences that consist of four alleles (A1, A2, A3, and A4) and six genotypes (A1/A2, A2/A2, A2/A3, A2/A4, A3/A4 and A4/A4) of the CYP2E1 gene. In the present study, we investigated whether these polymorphisms are associated with lung cancer and esophageal cancer. METHODS: DNA was isolated from blood samples of 192 healthy control subjects, 85 patients with lung cancer, and 82 patients with esophageal cancer in Japanese males. DNA samples were amplified by polymerase chain reaction in the 5'-flanking region of the CYP2E1 gene and in exon 12 in the ALDH2 gene. The tandem repeat polymorphisms were examined using DNA fragment analysis. Missense mutations in exon 12 of the ALDH2 gene were examined using fluorescence-based single strand conformational change polymorphism analysis. Written informed consent was obtained from all the subjects. RESULTS: In the CYP2E1 gene 5'-flanking region polymorphism, patients with esophageal cancer showed significantly higher frequency of the A4/A4 genotype compared with the control subjects (p = 0.02), but no difference was found in patients with lung cancer. The frequencies of the mutant ALDH2*2 allele were significantly higher in patients with esophageal cancer (27.7%) than in healthy control subjects (7.3%; p< 0.0001; habitual alcohol drinkers). CONCLUSIONS: The distribution of genotypes and allele frequencies of the tandem repeats of the 5'-flanking region of the CYP2E1 gene was significantly different in patients with esophageal cancer.

5' Flanking Region↗
PubMed2005

Mean corpuscular volume, alcohol flushing, and the predicted risk of squamous cell carcinoma of the esophagus in cancer-free Japanese men.

BACKGROUND: Because some of the causes of increased mean corpuscular volume (MCV) and esophageal squamous cell carcinoma (ESCC), including alcoholism, acetaldehyde exposure, smoking, and poor nutrition are common to both, macrocytosis has been used as a predictor of early ESCC in Japanese alcoholics. We examined whether this was also true in the Japanese general population. METHODS: This study compared the MCV of 522 cancer-free Japanese men with his risk of ESCC as defined using drinking, smoking, dietary habits and aldehyde dehydrogenase-2 (ALDH2) genotype in a previous case-control study of ESCC involving them as control subjects. RESULTS: MCV was significantly correlated with ESCC risk predicted by drinking combined with ALDH2 genotype, smoking, or fruit intake. Men at higher risk of ESCC were more frequent in the groups with higher MCV (p < 0.0001 for trend). The replies to a questionnaire about facial flushing in response to alcohol showed that the trend was more prominent in men with current/former flushing, a surrogate marker for inactive ALDH2, than in men with no flushing (p < 0.0001). In comparison with the mean risk of men with MCV < or = 93 fl (lowest quartile), that of current/former flushing men with MCV > or = 99 fl (highest quartile) was 6.35-fold higher, whereas that of never-flushing men with MCV > or = 99 fl was 2.50-fold higher. The sensitivity and specificity of the combination of moderate-to-heavy drinking and either MCV > or = 99 fl or current/former flushing, either 30+ pack-years or MCV > or = 99 fl or either 30+ pack-years or current/former flushing for detection of high-risk persons ranking in the top 10%, was 85% and 84%, 94% and 76%, or 98% and 77%, respectively. CONCLUSIONS: MCV and alcohol flushing might be used to better select candidates to screen this high-mortality-rate cancer not only in alcoholics but also in nonalcoholic Japanese men.

Adult↗