ADH1B与ALDH-2基因多态性与中国人群食管癌发病风险的Meta分析

目的探讨中国人乙醇脱氢酶1B(ADH1B)和乙醛脱氢酶-2(ALDH-2)的基因多态性与食管癌发病风险的关系。方法检索中外文数据库,获得有关ADH1B和ALDH-2位点的多态性与食管癌发病风险的病例-对照研究资料,对各位点以及与饮酒的交互作用进行Meta分析,得到合并的OR值及其95%CI。结果等位基因ADH1B*1和ALDH-2*2可增加食管癌的发病风险。基因型ADH1B*1/*2和ADH1B*1/*1的OR值分别为1.24(95%CI 1.10-1.41)和3.05(95%CI 1.94-4.77);基因型ALDH-2*1/*2和ALDH-2*2/*2的OR值分别为1.6(95%CI 1.01-2.03)和0.77(95%CI 0.28-2.09)。在饮酒人群中,与基因型ADH1B*2/*2相比,ADH1B*1/*2+*2/*2的OR=3.13(95%CI 2.17-4.51);与基因型ALDH-2*1/*1相比,ALDH-2*1/*2+*2/*2的OR=4.12(95%CI 1.98-8.56)。结论在中国人群中,等位基因ADH1B*1和ALDH-2*2均能增加食管癌患病的风险,且饮酒可以增加这一风险。     

Alcohol drinking, mean corpuscular volume of erythrocytes, and alcohol metabolic genotypes in drunk drivers

Regular and irregular abuse of alcohol are global health priorities associated with diseases at multiple sites, including cancer. Mechanisms of diseases induced by alcohol are closely related to its metabolism. Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]). Whether these genetic variants can influence abuse in alcohol drinking and MCV has never been examined in drunk-driving traffic offenders. We examined 149 drunk drivers, diagnosed as alcohol abusers according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition Text Revision (DSM-IV-TR) and enrolled in a probation program, and 257 social drinkers (controls), all Caucasian males. Alcohol intake was assessed according to self-reported drink-units/d and MCV unadjusted and adjusted for age, smoking, and body mass index. Multivariable models were used to compute MCV adjusted means. Genotype analyses were performed by PCR on DNA from blood. The adjusted MCV mean was higher in drunk-driving abusers than in controls (92 vs. 91 fL; P < .0001) and increased with the number of drink-units/d in both abusers and controls (P-trend = .0316 and .0089) already at intermediate quantities (0-1 vs. 2-4 drink-units/d: P = .054 and .024). Carriers of the common ADH1B*1/*1 (rs1229984) genotype were more likely to be drunk-driving abusers (P = .008), reported higher drink-units/d (P = .0126), and had larger MCV (P = .035). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with MCV. ADH1B*1/*1 polymorphism is significantly associated with being a drunk-driving abuser, higher alcohol drinking, and MCV enlargement. This suggests that drunk drivers with augmented MCV modulated by the alcohol metabolic ADH1B*1/*1 genotype may be at higher risk of driving incapability and of alcohol-related cancer.     

A comparison of Val81Met and other polymorphisms of alcohol metabolising genes in patients and controls in Northern Spain

The aim of this paper is to study polymorphism in the TH, ADH1B, ADH1C, ALDH2 and CYP2E1 genes so as to ascertain whether it is associated with excessive consumption of alcohol. The SNPs rs6356 of TH, rs1229984, rs2066702 of ADH1B; rs698, rs1693482 of ADH1C; rs671 of ALDH2; rs72559710, rs55897648, rs6413419, rs3813867, rs2031920, rs6413432 of CYP2E1 were studied in a sample of 172 high-level patients and 150 fully non-drinkers controls. Genotyping was performed using Rt-PCR with Taqman probes. SNPs located at ALDH2 and CYP2E1 showed no heterozygosity. Frequency distribution showed significant differences between the two groups studied for loci TH and ADH1B. The genotype Val/Val of TH locus increased in risk 1.988 times (95% CI: 1.006–3.930) that the subjects carrying the genotype Met/Met; and the genotype ADH1B*1/*1 of ADH1B locus increased in risk 3.811 times (CI: 1.660–8.749) that the subjects carrying the genotype ADH1B*1/*2. Alleles Val and ADH1B*1 may therefore increase the risk of the onset and development of this illness.     

Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was to systematically determine the functional expressions and cellular localization of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and hemorrhoid, and the genetic association of allelic variations of ADH and ALDH with large bowel disorders. Twenty-one surgical specimens of rectal adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of rectal tumor, normal mucosae of rectum and sigmoid colon from the same individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control subjects recruited in previous study, were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies; the cellular activity and protein localizations were detected by immunohistochemistry and histochemistry, respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphisms. At 33 mM ethanol, pH 7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at 200 μM acetaldehyde. The protein contents in normal rectal mucosa were in the following order: ADH1 > ALDH2 > ADH3 ≈ ALDH1A1, whereas those of ADH2, ADH4, and ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly decreased in rectal tumors, whereas the ALDH activity remained unchanged. The ADH activity was also significantly reduced in hemorrhoids. ADH4 and ALDH3A1 were uniquely expressed in the squamous epithelium of anus at anorectal junctions. The allele frequencies of ADH1C*1 and ALDH2*2 were significantly higher in colorectal cancer and that of ALDH2*2 also significantly greater in hemorrhoids. In conclusion, ADH and ALDH isozymes are differentially expressed in mucosal cells of rectum and anus. The results suggest that acetaldehyde, an immediate metabolite of ethanol, may play an etiological role in pathogenesis of large bowel diseases.     

Relationships of alcohol dehydrogenase 1B (<Emphasis Type="Italic">ADH1B</Emphasis>) and aldehyde dehydrogenase 2 (<Emphasis Type="Italic">ALDH2</Emphasis>) genotypes with alcohol sensitivity,drinking behavior and problem drinking in Japanese older men

Objectives

Many East Asians have the genetic polymorphisms rs1229984 in alcohol dehydrogenase 1B (ADH1B) and rs671 in aldehyde dehydrogenase 2 (ALDH2). Here we analyzed the relationships of the two genotypes with alcohol sensitivity, drinking behavior and problem drinking among older and younger men living in rural areas of Japan.

Methods

The subjects were 718 Japanese men aged 63.3 ± 10.8 (mean ± SD), categorized into the older (≥65 years, n = 357) and younger (<65 years, n = 361) groups. Facial flushing frequency, drinking behavior and positive CAGE results were compared among the genotypes using Bonferroni-corrected χ² test and a multivariate logistic regression analysis adjusting for age, BMI and lifestyle factors.

Results

The frequency of ‘always’ facial flushing among the ADH1B*1/*2 carriers was significantly lower than that among the ADH1B*2/*2 carriers in the older group (P < 0.01). The alcohol consumption (unit/day) in the ADH1B*1/*2 carriers tended to be higher compared with that in the ADH1B*2/*2 carriers among the older group (P = 0.050). In the younger group, no significant differences in alcohol sensitivity and drinking habits were generally found among the ADH1B genotypes. The ADH1B*1/*1 genotype tended to be positively associated with problem drinking in the older group (P = 0.080) but not in the younger group. The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group.

Conclusions

We for the first time observed a significant difference in alcohol sensitivity between ADH1B*1/*2 and ADH1B*2/*2 in older men aged 65 and above.

     

Gene-environmental interactions in alcohol-related health problems--contributions of molecular biology to behavior modifications

High alcohol sensitivity among Asians is mainly due to a genetic polymorphism in the low Km aldehyde dehydrogenase (ALDH2) gene. Strong correlations between the ALDH2 genotype and alcohol sensitivity or alcohol drinking habits have been reported. Another prevalent polymorphism in the alcohol dehydrogenase beta-subunit (ADH2 gene) among Asians appears to modify skin flushing reactions after exposure to ethanol but does not influence alcohol drinking behavior. Both the ADH2 and ALDH2 genotypes have been significantly correlated with the risk of alcoholism. In a Japanese occupational population, a gene-environment interaction of the ALDH2 genotype and daily hassles scores for development of problem drinking behavior was observed. Habitual drinkers with the ALDH2*1/*2 genotype had higher frequencies of sister-chromatid exchange in cultured lymphocytes and higher 8-OHdG levels in polymorphonuclear leukocytes than those with the ALDH2*1/*1 genotype. Alcoholics and heavy drinkers with the ALDH2*1/*2 genotype have been shown to have significantly elevated risks for esophageal and multiple cancers in upper digestive organs than those with the ALDH2*1/*1 genotype. In Japan, bronchial asthma patients with the ALDH2*1/*2 genotype have been shown to have a significantly elevated risk for experiencing alcohol-induced asthma compared with the ALDH2*1/*1 genotype. Providing services to determine these genotypes would be of great help for each individual to make a plan for tailor-made health promotion.     

Distribution of ADH1B, ALDH2, CYP2E1∗6, and CYP2E1∗7B genotypes in Turkish population

The most well-known metabolic pathways from ethanol to acetaldehyde include alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system that involves cytochrome P450 2E1 (CYP2E1). Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH). The genetic variation of ADH1B, ALDH2, and CYP2E1 is different among racial populations and cause difference in elimination rates of alcohol. The aim of this study was to determine the polymorphisms of ADH1B (rs1229984; Arg47His), ALDH2 (rs671; Glu487Lys), CYP2E1*6 (rs6413432; T7632A), and CYP2E1*7B (rs6413420; G-71T) in unrelated healthy Turkish population and compare it with other populations. ADH1B and ALDH2 polymorphisms were analyzed with an allele-specific polymerase chain reaction (PCR) assay, and CYP2E1*6 and CYP2E1*7B polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. ADH1B polymorphism analysis yielded the genotype distribution as 83.9% ADH1B*1/1 and 16.1% ADH1B*1/2, and no individuals with ALDH2*1/2 and ALDH2*2/2 genotypes were found in Turkish population. The genotype frequencies for CYP2E1*6 polymorphism were found as 85.3% for homozygote common, 14.1% for heterozygote, and 0.6% for homozygote uncommon. For CYP2E1*7B polymorphism, the genotype frequencies were determined to be 86.5% G/G, 13.5% for G/T; however, no individuals with homozygote uncommon genotype were detected. According to our study results, the genotype distributions of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B in Turkish population were similar compared with Caucasian and some European populations, whereas differed significantly from East Asian populations. This study may be useful in epidemiological studies of the influence of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B polymorphisms on diseases, including several types of cancer related to alcohol consumption and alcohol dependence.     

Is ADH1C genotype relevant for the cardioprotective effect of alcohol?

The cardioprotective effect of ethanol has been suggested to be linked to one of the ethanol metabolizing enzymes (ADH1C), which constitutes a high V_max and a low V_max variant. This has been demonstrated in some studies, while others have not been able to replicate the findings. The aim of the present study was to investigate the relation between the different ADH1C genotypes, death from coronary heart disease (CHD) and alcohol in a material larger than the previously published studies. Eight hundred CHD deaths as well as 1303 controls were genotyped for the high V_max (γ1) and the low V_max (γ2) ADH1C variant. Information of alcohol use was available for all subjects. Multiple logistic regression analyses was used to study if the decreased risk of death from CHD in alcohol consuming subjects was more pronounced in subjects homozygous for the γ2 allele (γ2γ2 subjects) compared to γ1γ1 and γ1γ2 subjects. The odds ratio (OR) for death from CHD in alcohol consumers compared to abstainers was similar in the genotype groups, i.e., 0.62 (95% CI: 0.43–0.88) in γ1γ1 subjects and 0.62 (95% CI: 0.42–0.91) in γ2γ2 subjects. Also when stratifying the results by gender and when dividing alcohol consumers into different alcohol consumption groups, there was no difference in the OR between the different genotype groups. This study, which included the largest study group published so far, failed to find any link between the ADH1C genotype and the cardioprotective effects of alcohol.     

Interactions between alcohol intake and the polymorphism of rs708272 on serum high-density lipoprotein cholesterol levels in the Guangxi Hei Yi Zhuang population

Both alcohol consumption and the polymorphism of the cholesteryl ester transfer protein (CETP) TaqIB gene (rs708272) influence plasma high-density lipoprotein cholesterol (HDL-C) levels. However, their interactions on serum HDL-C levels is not well known. The present study was undertaken to detect the interactions between alcohol consumption and the rs708272 polymorphism on serum lipid levels in the Guangxi Hei Yi Zhuang population. Genotyping of the rs708272 in 342 nondrinkers and 416 drinkers aged 15-70 years was performed by polymerase chain reaction and restriction fragment length polymorphism. Interactions between rs708272 genotype and alcohol consumption was assessed using a cross-product term between genotypes and the aforementioned factor. Statistical significance was evaluated with analysis of co-variance. The frequency of B1 allele was 65.8% in nondrinkers and 64.7% in drinkers (P > .05), respectively. The frequencies of B1B1, B1B2, and B2B2 genotypes were 45.0%, 41.5%, and 13.5% in nondrinkers, and 41.3%, 46.6%, and 12.0% in drinkers (P > .05), respectively. The levels of HDL-C and apolipoprotein (Apo) AI in nondrinkers were higher in B2B2 genotype than in B1B1 genotype (P < .05 for each), whereas triglyceride (TG) levels in drinkers were higher in B1B1 genotype than in B1B2 genotype (P < .05). The levels of TG, HDL-C, Apo AI in B1B1 genotype, and HDL-C and Apo AI in B1B2 genotype were higher in drinkers than in nondrinkers (P < .05-.01), whereas the levels of low-density lipoprotein cholesterol (LDL-C) and Apo B in B2B2 genotype, and the levels of LDL-C in B1B1 genotype were lower in drinkers than in nondrinkers (P < .05-.01). The levels of HDL-C were positively correlated with female sex and genotype in nondrinkers (P < .001 for each), and were positively associated with age and alcohol consumption in drinkers (P < .005 and < .01, respectively). This study suggests that the B1 carriers benefited more from alcohol consumption than the B2 carriers in increasing serum HDL-C and Apo AI levels, and lowering LDL-C levels.     

Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.     

乙醇和乙醛脱氢酶基因多态与食道癌易感性

目的 研究乙醇脱氢酶2(ADH2)和乙醛脱氧酶2(ALDH2)基因多态与食道癌易感性.方法 对江苏省泰兴市221例食道癌新发病例和191名对照的饮酒习惯等因素进行调查,采用PCR和变性高效液相色谱法(DHPLC)检测ADH2和ALDH2基因型.结果 (1)与携带ALDH2 G/G基因型者相比,携带ALDH2A/A(OR=5.69,95%CI:2.51～12.18)和ALDH2 G/A(OR=1.70,95%CI:1.08～2.68)基因型者患食道癌危险性明显增加,以携带ALDH2A/A的饮酒者最为显著(OR=8.63,95%CI:2.07～35.95).(2)无论是否饮酒,携带不同ADH2基因型者之间患食道癌的风险差异均无统计学意义.(3)携带ALDH2 A/A或G/A基因型者,不论同时携带何种ADH2基因型患食道癌的风险均显著增加,且作用效应为ALDH2 A/A≥G/A.(4)与同时携带ALDH2 G/G和ADH2 A/A的不饮酒者相比,同时携带ALDH2 G/A或A/A和ADH2 G/A或G/G的饮酒者,患食道癌危险性OR值高达8.36(95%CI:2.98～23.46).结论 饮酒及醇醛脱氢酶基因多态与食道癌的联系主要与ALDH2有关;携带ALDH2A/A和G/A者减少酒精消耗量,有助于降低患食道癌危险性.     

Genetic polymorphism of alcohol dehydrogenase 3 in alcohol liver cirrhosis and in alcohol chronic pancreatitis

AIM: To find the ADH3 genotypes in the Polish population likely to be responsible for higher susceptibility to alcohol disease of the liver and chronic alcohol pancreatitis. METHOD: The ADH3 genotype and ADH3*1 and ADH3*2 alleles frequencies were examined in 198 patients. Genotyping of the ADH3 was performed using PCR-restriction fragment length polymorphism methods on a white cell DNA. RESULTS: The genotype ADH3*1/ADH3*1 was found to be significantly more frequent in alcohol abusers compared with non-drinkers. The examinations of the group of alcohol abusers showed that the genotype ADH3*2/ADH3*2 occurred statistically significantly less frequently in patients with chronic pancreatitis than in those without alimentary lesions (healthy drinkers). The alleles ADH3*1 and genotype ADH3*1/ADH3*1 were significantly more frequent in men than in women, whereas alleles ADH3*2 and genotype ADH3*2/ADH3*2 were more common in women. CONCLUSIONS: The genotype ADH3*2/ADH3*2 is likely to be a protective factor for chronic pancreatitis. Variations in ADH3 genotypes may account for some of the differences in prevalence of alcohol dependence between genders in the Polish population.     

Meta-Analysis of the Association between Dietary Inflammatory Index (DII) and Colorectal Cancer

The Dietary Inflammatory Index (DII) was extensively used to examine the inflammatory potential of diet related to colorectal cancer (CRC). This meta-analysis aimed to update the evidence of the association between the DII and CRC across various culture-specific dietary patterns. Literature search was performed through online databases (Scopus, Web of Science, PubMed, and EBSCOHost). Observational studies exploring the association between the DII and CRC, published between 2017 and 2021, were included. The risk ratio (RR) and 95% confidence interval (CI) were separately computed for 12 studies comparing the highest and lowest DII scores and for 3 studies that presented continuous DII scores. A high DII score was associated with a higher risk of CRC (RR:1.16; 95% CI, 1.05–1.27). In the subgroup analysis, significant associations were seen in cohort design (RR: 1.24; 95% CI, 1.06–1.44), those lasting for 10 years or longer (RR: 2.95; 95% CI, 2.47–3.52), and in adjustment factor for physical activity (RR: 1.13; 95% CI, 1.07–1.20). An increase of one point in the DII score elevates the risk of CRC by 1.34 (95% CI: 1.15–1.55) times. The findings call for standardized measurement of the inflammatory potential of diet in future studies to enable the establishment of global guidelines for CRC prevention.     

Genetic factors which regulate alcohol drinking behavior and their effects on health status]

High alcohol sensitivity common among Orientals is mainly due to genetic polymorphism in the low K(m) aldehyde dehydrogenase (ALDH2) gene. The relation of the ALDH2 genotype to alcohol sensitivity and drinking behavior was investigated in a Japanese occupational population. The frequency of alcohol-associated symptoms generally increased in the order of the typical homozygote, heterozygote, and atypical homozygote. Both drinking frequency and amounts of alcohol consumption were also significantly affected by the polymorphism. Polymorphism in the alcohol dehydrogenase beta-subunit (ADH2 gene) appeared to contribute to skin flushing post-alcohol exposure but not to alcohol drinking behavior. Multivariate analysis revealed that high alcohol consumption, the ALDH2*1/*1 genotype, and high daily hassles levels significantly contribute to the prevalence of those with a high problem-drinking score in an occupational population. In the study to assess the effects of the ALDH2 polymorphism and alcohol use on the induction of chromosome alterations in peripheral lymphocytes, we found that lymphocytes from habitual drinkers with the atypical ALDH2 genotypes had significantly higher frequencies of sister-chromatid exchange (SCE) than those from the typical ALDH2 genotype. We also measured acetaldehyde reversibly bound to hemoglobin (HbAA). In volunteers with the ALDH2*1/*2 genotype, the HbAA levels increased immediately after the drink and the elevated levels persisted up to 48 h. Among male workers, HbAA levels were significantly correlated with the recent alcohol consumption levels in both the ALDH2*1/*1 and ALDH2*1/*2 genotypes. However, the slope was much steeper in the ALDH2*1/*2 than in the ALDH2*1/*1. SCE and HbAA may be utilized as a good biomarker for health problems in the atypical ALDH2 genotype. Further extensive studies are required for evaluation of the interactive effects of genetic and environmental factors on alcohol-related health problems.     

中国人群饮酒与代谢综合征发病关系的前瞻性研究

目的研究我国成年人饮酒状况对代谢综合征（MS）发病的影响。方法本项目为前瞻性队列研究。2007至2008年对分别于1998和2000年基线调查的中国心血管病流行病学多中心协作研究35～74岁的27020例队列人群开展随访调查。结果基线14572例非MS人群经8年随访,共发生MS2362例。在调整了年龄、南北方、城乡、受教育程度、体力活动、吸烟、体质指数以及MS组分数后,和不饮酒者相比,男性饮酒者发生MS的相对危险度（RR）为1．24（95％CI：1．06～1．45）,人群归因危险度为10．13％;每日摄入酒精量10．1～20g,20．1—40g,〉40g组的RR分别为1．36（95％CI：1．02～1．82）,1．34（95％CI：1．03—1．74）和1．41（95％CI：1．13,～1．77）;每周饮酒2～5次和／〉6次的RR分别为1．25（95％CI：1．01～1．55）和1．26（95％CI：1．04～1．52）;只喝啤酒组、只喝白酒组和混合饮酒组的RR分别为1．60（95％CI：1．05～2．45）、1．30（95％CI：1．02～1．65）和1．27（95％CI：1．06～1．52）。女性每日摄入酒精量在10．1～20g组和〉20g组RR分别为2．67（95％CI：1．26—5．65）和2．38（95％CI：1．35—4．22）。结论在全人群中,每13摄入酒精量〉10g就会显著增加MS发病风险,在女性中尤为明显。男性每周饮酒≥2次以及只饮啤酒、只饮白酒和混合饮酒者均明显升高MS的发病风险。为减少MS的流行,应提倡限制酒精过量摄入,尤其女性更应限制酒精摄入量（≤10g／d）。     

Alcohol, smoking, and body size in relation to incident Hodgkin's and non-Hodgkin's lymphoma risk

Studies associate alcohol consumption, cigarette smoking, and body size with the risk of overall or subtype lymphoma. Current data come mostly from case-control studies or prospective studies with few cases. In the prospective National Institutes of Health-former American Association of Retired Persons (NIH-AARP) Diet and Health Study, the authors assessed the above lifestyle factors via baseline questionnaire among 285,079 men and 188,905 women aged 50-71 years and ascertained histologically confirmed Hodgkin's lymphoma (n = 58) and non-Hodgkin's lymphoma (n = 1,381) cases through linkage with cancer registries from 1995 to 2000. Compared with nondrinkers, alcohol consumers had a lower risk for non-Hodgkin's lymphoma overall (for >28 drinks/week: adjusted relative risk (RR) = 0.77, 95% confidence interval (CI): 0.59, 1.00; p(trend) among drinkers = 0.02) and for its main subtypes. Compared with never smokers, current smokers and recent quitters (or=35: RR = 1.29, 95% CI: 1.02, 1.64) and taller height (RR = 1.19, 95% CI: 1.03, 1.38) were associated moderately with non-Hodgkin's lymphoma. These findings add to the evidence that lifestyle factors and relevant anthropometric characteristics play a role in lymphoma etiology.     

Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences

Alcohol abuse is an important public health problem. In Portugal with a population of 10 millions of inhabitants, there are around 10% of alcoholics or excessive alcohol drinkers and 1% of chronically infected patients with hepatitis B virus (HBV). To examine the characteristics of patients with higher levels of alcohol consumption and to investigate the association between alcohol consumption and liver damage a total of 298 chronically infected individuals, with HBV genotyped and submitted to liver biopsy, were classified with Child's grading and separated by habits of alcohol intake, less and greater than 20 g/day. No significant differences were observed about genotype but genotypes A and D were predominant in both of them. A higher percentage of males (P < .001) were observed in the group with alcohol intake above 20 g/day, as well a lower proportion of patients with HBeAg negativity (P ≤ .035). In this group, biochemistry parameters, such as alanine aminotransferase (P = .006), aspartate aminotransferase (P = .001), gamma-glutamyl transferase (P < .001) were elevated in a significantly higher proportion than in the other group. The analysis of hematological parameters showed significantly lower values of platelets (P = .042) and mean corpuscular volume (P < .001) and significantly higher values of prothrombin time (P < .001) in the group with higher levels of alcohol consumption. The characteristics of biopsy (P < .001) and Child-Phug's classification (P = .002) revealed more severe results in this group. Logistic regression showed a positive association between liver damage and alcohol intake, increasing with age. In female patients, a strong positive association between alcohol intake and liver damage was also found (odds ratio: 9.379; 95% confidence interval: 0.859-468.422; P = .037); however, the most severe cases were only observed in women older than 45 years. In patients with HBV infection, alcohol is associated with a more severe liver disease. No evidence was found concerning association with HBV genotype.     

Association of genotypes of carcinogen-metabolizing enzymes and smoking status with bladder cancer in a Japanese population

Objectives

Arylamines are considered to be the primary causative agent of bladder cancer in tobacco smokers. To test the hypothesis that variation in the genes that metabolize tobacco carcinogens contribute to bladder cancer, we examined the effects of single nucleotide polymorphisms in the genes of four key enzymes: cytochrome P450 1A2, N-acetyltransferase (NAT) 2, sulfotransferase 1A1, and UDP-glucuronosyltransferase (UGT) 2B7.

Methods

In this study, 282 Japanese patients with transitional cell carcinoma, the most common bladder cancer, and 257 healthy controls were surveyed and compared for frequencies of the genotypes of the four enzymes. Genotypes were determined using PCR-restriction fragment length polymorphism and TaqMan assays. Smoking information was collected by personal interview. Logistic regression analysis and the chi-square test were employed as statistical methods.

Results

The NAT2 slow genotype was significantly associated with the risk of bladder cancer [odds ratio (OR) 3.41, 95 % confidence interval (95 % CI) 1.68–6.87; p < 0.05). The NAT2 slow genotype also significantly increased the risk of bladder cancer in heavy smokers (OR 8.57, 95 % CI 1.82–40.25; p < 0.05). Among the different combinations of the four enzyme genotypes, the highest OR (4.20; 95 % CI 1.34–13.14; p < 0.05) was obtained with the NAT2 slow genotype when present in combination with the UGT2B7 *2/*2 or *1/*2 genotype.

Conclusions

Our results suggest that individuals with different genotypes for the enzymes involved in metabolizing carcinogenic arylamines have a different risk of developing bladder cancer. In particularly, the combination of the NAT2 slow genotype with UGT2B7 *1/*2 or *2/*2 genotype is a high risk factor for bladder cancer.     

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.     

Hazardous alcohol consumption and aging synergistically increase the risk of death in patients with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case fatality rate (CFR). Alcohol consumption which impairs host immunity and contributes to tissue damage in a variety of organs may be a predisposing factor of fatal outcome in SFTS. We aimed to determine the role of alcohol consumption on the fatal outcome of SFTS. Patients with laboratory-diagnosed SFTS who were admitted to the Jinan Infectious Disease Hospital, Jinan, China, between January 2011 and November 2018 were evaluated. Demographic, clinical, and laboratory data were recorded. Alcohol consumption was evaluated. The association between a fatal outcome and each demographic, clinical, and laboratory variable with alcohol consumption was assessed. A total of 694 patients with SFTS were identified during the study period. The overall CFR was 20.9 % (95 % CI: 17.9 %–23.9 %). The CFR in non/light drinkers (0−98 g/week) and moderate/heavy drinkers (>98 g/week) was 18.3 % and 35.6 %, respectively (P < 0.001). In age>60 years patients, the overall CFR in moderate/heavy drinker groups were as high as 53.4 % (95 % CI:40.2 %–66.7 %). Comparing to the age≤60y and non/light drinkers, age>60y and moderate/heavy drinkers was associated with increased risk of death with an odds ratio (95 % CI) of 9.9 (5.1–19.1). The interaction between age>60 and alcohol consumption was a significant determinant for death in both genders (F=10.18, P = 0.001). The clinical manifestation, laboratory parameters, and organ injury were significantly extensive and severe in moderate and heavy drinkers. In conclusion, hazardous alcohol consumption and aging synergistically increase the risk of death in patients with SFTS. In SFTS endemic areas, it is important for older individuals to minimize the exposure risks and abstain from alcohol.