Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2) and/or aldehyde dehydrogenase 2 (ALDH2) for risk of colorectal cancer (CRC) in Chinese males. METHODS: A case-control study was conducted in 190 cases and 223 population-based controls. ADH2 Arg47His (G-A) and ALDH2 Glu487Lys (G-A)genotypes were identified by PCR and denaturing high-performance liquid chromatography (DHPLC). Information on smoking and drinking was collected and odds ratio (OR) was estimated. RESULTS: The ADH2 A/A and ALDH2 G/G genotypes showed moderately increased CRC risk. The age- and smoking-adjusted OR for ADH2 A/A relative to G/A and G/G was 1.60 (95% CI=1.08-2.36), and the adjusted OR for ALDH2 G/G relative to G/A and A/A was 1.79 (95% CI=1.19-2.69). Signif icant interactions between ADH2, ALDH2 and drinking were observed. As compared to the subjects with ADH2 G and ALDH2 A alleles, those with ADH2 A/A and ALDH2 G/G genotypes had a signif icantly increased OR (3.05, 95% CI= 1.67-5.57). The OR for CRC among drinkers with the ADH2 A/A genotype was increased to 3.44 (95% CI= 1.84-6.42) compared with non-drinkers with the ADH2 G allele. The OR for CRC among drinkers with the ALDH2 G/G genotype was also increased to 2.70 (95% CI= 1.57-4.66) compared with non-drinkers with the ALDH2 A allele. CONCLUSION: Polymorphisms of the ADH2 and ALDH2 genes are significantly associated with CRC risk. There are also signifi cant gene-gene and gene- environment interactions between drinking and ADH2 and ALDH2 polymorphisms regarding CRC risk in Chinese males.

ADH1B与ALDH2在胃癌组织中的表达及其临床意义

目的探讨乙醇脱氢酶1B(alcohol dehydrogenase 1B,ADH1B)与乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)在胃癌组织中的表达及其临床意义。方法选取2017年05月至2019年10月期间在滁州市第一人民医院接受根治性切除的132例胃癌患者为研究对象,通过免疫组织化学染色(Immunohistochemistry,IHC)检测ADH1B与ALDH2在胃癌及癌旁组织中的表达。分析ADH1B、ALDH2表达与患者临床病理特征的关系,采用Kaplan-Meier曲线评估两者表达在胃癌中的预后价值。单、多变量Cox回归分析用于确定胃癌患者的独立预后因素。结果对132例组织样本的IHC分析显示ADH1B(41.5%vs 58.5%,χ^(2)=9.594,P=0.002)与ALDH2(38.8%vs 61.2%,χ^(2)=16.716,P<0.001)在胃癌组织中的阳性表达率显著低于其癌旁组织。与高表达组相比,ADH1B低表达在T_(3)-T_(4)期(χ^(2)=5.572,P=0.018)、pTNMⅢ期肿瘤(χ^(2)=4.675,P=0.031)中更为常见,淋巴血管侵犯率更高(χ^(2)=4.566,P=0.033)。ALDH2在低分化癌(χ^(2)=4.261,P=0.039)和pTNMⅢ期胃癌(χ^(2)=5.877,P=0.015)中表达更低,淋巴结转移率(χ^(2)=5.491,P=0.019)较高表达者更为频繁。生存分析表明ADH1B与ALDH2低表达是胃癌患者预后不良的标志。ADH1B低、高表达患者的3年总体生存(Overall survival,OS)率分别为52.3%和73.9%(χ^(2)=6.900,P=0.009),ALDH2低、高表达患者的3年OS率分别为49.8%和74.4%(χ^(2)=8.665,P=0.003)。ADH1B(HR=2.115,95%CI:1.133-3.946,P=0.019)与ALDH2低表达(HR=2.296,95%CI:1.207-4.367,P=0.011)是胃癌患者的独立预后因素。结论ADH1B与ALDH2在胃癌组织中呈明显低表达,两者可能是预测肿瘤进展与患者预后的分子标志物。

Aldehyde dehydrogenase 2 overexpression inhibits neuronal apoptosis after spinal cord ischemia/reperfusion injury

Aldehyde dehydrogenase 2（ALDH2）is an important factor in inhibiting oxidative stress and has been shown to protect against renal ischemia/reperfusion injury.Therefore,we hypothesized that ALDH_2 could reduce spinal cord ischemia/reperfusion injury.Spinal cord ischemia/reperfusion injury was induced in rats using the modified Zivin＇s method of clamping the abdominal aorta.After successful model establishment,the agonist group was administered a daily consumption of 2.5%alcohol.At 7 days post-surgery,the Basso,Beattie,and Bresnahan score significantly increased in the agonist group compared with the spinal cord ischemia/reperfusion injury group.ALDH_2expression also significantly increased and the number of apoptotic cells significantly decreased in the agonist group than in the spinal cord ischemia/reperfusion injury group.Correlation analysis revealed that ALDH_2 expression negatively correlated with the percentage of TUNEL-positive cells（r=-0.485,P〈0.01）.In summary,increased ALDH_2 expression protected the rat spinal cord against ischemia/reperfusion injury by inhibiting apoptosis.

Association of genetic polymorphisms of aldehyde dehydrogenase-2 with esophageal squamous cell dysplasia

AIM:To demonstrate the possible associations between genetic polymorphisms of aldehyde dehydrogenase-2(ALDH2) and esophageal squamous cell dysplasia(ESCD).METHODS:All participants came from an area of high incidence of esophageal cancer and underwent an endoscopic staining examination;biopsies were taken from a non-staining area of the mucosa and diagnosed by histopathology.Based on the examinations,the subjects were divided into the control group with normal esophageal squamous epithelial cells and the ESCD group.ALDH2 genotypes of 396 cases were determined including 184 ESCD cases and 212 controls.The odds ratio(OR) and 95% confidence intervals(95% CI) were calculated by binary logistic regression models.RESULTS:The distribution of ALDH2 genotypes showed significant differences between the two groups.The adjustment factors were gender and age in the logistic regression models.Compared with 2*2/2*2 genotype,2*1/2*1 genotype was found to be a risk factor for ESCD,and the OR(95% CI) was 4.50(2.21-9.19).There were significant correlations between ALDH2 genotypes and alcohol drinking/smoking/history of esophageal cancer.CONCLUSION:The ALDH2 polymorphism is significantly associated with ESCD.

洛阳市汉族群体ADH2和ALDH2的基因多态性研究

为研究洛阳市汉族群体ADH2和ALDH2基因的多态性分布,应用聚合酶链反应-扩增片段长度多态性（PCR-APLP）分析法,对ADH2基因外显子3和ALDH2基因外显子12的特定片段同时进行特异性扩增,用非变性的聚丙烯酰胺垂直凝胶电泳和DNA银染方法判定基因型。ADH2＊1和ADH2＊2等位基因频率分别为42.86％和57.14％,ADH2＊1/＊1、＊1/＊2和＊2/＊2的基因型频率分别为22.86％、40.00％和37.14％;AL-DH2＊1和ALDH2＊2的等位基因频率分别为85.24％和14.76％,ALDH2＊1/＊1、＊1/＊2和＊2/＊2的基因型频率分别为71.43％、27.62％和0.95％。洛阳市汉族群体ADH2和ALDH2的等位基因频率和基因型频率不同于台湾人和上海人,ALDH2＊1/＊1基因型频率明显高于上海人和台湾人的。因而,洛阳市居民对酒精的耐受性比上海人和台湾人强。

鸡枞菌多糖对急性酒精肝损伤小鼠超微病理结构及ADH2、ALDH2 mRNA表达的影响

目的:从小鼠肝脏超微病理结构及酒精代谢相关酶乙醇脱氢酶2(alcohol dehydrogenase 2,ADH2)、乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)的m RNA表达方面研究鸡枞菌多糖(refined polysaccharides from Termitomyces albuminosus,RPTA)对酒精所致小鼠急性肝损伤的保护作用。方法:小鼠被随机分为空白对照组、模型对照组、药物对照组(联苯双酯组,150 mg/(kg·d))、RPTA各剂量组(1 00、200、400 mg/(kg·d)),连续灌胃30 d,空白对照组灌胃等量生理盐水。第31天,给予50%乙醇(12 m L/kg)建立动物急性肝损伤模型。12 h后处死,取小鼠肝脏分别观察肝组织超微结构变化,并采用荧光实时定量聚合酶链式反应(real time polymerase chain reaction,real time-PCR)法检测肝脏ADH2和ALDH2的m RNA表达。结果:超微结构观察结果表明,模型对照组小鼠肝脏细胞内可见大量脂滴,细胞核呈不规则形态,局部核膜凹陷严重,线粒体严重变形,线粒体嵴模糊,内质网严重肿胀,核糖体脱落;而RPTA小鼠肝细胞内上述病变有所改善,尤以高剂量组最佳。Real time-PCR结果表明,与空白对照组相比,模型对照组ADH2和ALDH2的m RNA表达量降低,而RPTA组随着剂量的增加ADH2和ALDH2 m RNA的表达逐渐升高。结论:RPTA可以上调ADH2和ALDH2 m RNA的表达,具有改善小鼠酒精性肝损伤状况的作用。

AS-PCR在ADH2、ALDH2基因多态型分析中的应用

[目的 ]为获得更为简便经济同时精确度足够高的酒精脱氢酶 2 (ADH2 )和乙醛脱氢酶 2 (ALDH2 )基因多态型测定的新方法。 [方法 ]建立并优化等位基因特异性PCR(allelespecific PCR ,AS PCR)方法 ,通过与经典PCR RFLP方法的分型结果相比较考察其可行性。 [结果 ]AS PCR方法对 60例DNA样本的ADH2、ALDH2基因的分型结果与PCR RFLP法完全一致 ,且简便快速 ,成本低 ,特异性和准确度也足够高。 [结论 ]AS PCR方法分析ADH2、ALDH2基因多态型优点明显 。

乙醇依赖综合征与ADH2、CYP4502E1基因多态性的相关研究

目的对云南汉族酒依赖综合征与ADH2、CYP4502E1基因多态性进行相关性研究;方法采用PCR-RFLP方法,对来自云南地区的44例乙醇依赖综合征患者以及与其配比的30例对照个体的ADH2基因第3外显子处G143A单核苷酸多态位点等位基因频率和基因型频率、CYP2E1基因5′端非编码区的RsaI/PstI酶切位点多态性等位基因频率和基因型频率以及是否与乙醇依赖综合征相关进行分析。结果(1)在患者组ADH2基因3种基因型ADH2*1/*1、ADH2*1/*2、ADH2*2/*2分别为36%、43%、21%,患者组和对照组相比较无显著差异(P>0.05);等位基因ADH2*1和ADH2*2在患者组中的基因频率为0.58和0.42,患者组和对照组相比较分布有差异(P<0.05),患者组ADH2*2等位基因频率降低;(2)CYP2E1基因在患者组中A、B型基因分布为59%、41%,患者组和健康对照组两种基因型的分布有差异(P<0.05),B型基因在乙醇依赖组升高;等位基因c1和c2在患者组中的频率为0.80和0.20,患者组和对照组两种等位基因分布有差异(P<0.05),患者组c2等位基因频率升高。结论CYP2E1基因多态性与乙醇依赖综合征发生有关,ADH2*2等位基因对于乙醇依赖综合征发病有保护作用,而c2等位基因在乙醇依赖综合征的发生中起一定的作用。

ALDH2和ADH1B基因多态性与食管癌淋巴结转移的相关性

目的:研究中国汉族人群中乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)和乙醇脱氢酶1B(alcohol dehy-drogenase 1B,ADH1B)基因多态性与食管癌淋巴结转移风险性的关系。方法:采用基质辅助激光解吸电离飞行时间质谱(matrix-assisted laser desorption/ionization-time of flight mass spectrometry,MALDI-TOF MS)技术分析85例有淋巴结转移的食管癌和270例无淋巴结转移的食管癌标本ALDH2 rs671和ADH1B rs1229984基因多态性,计算各种基因型与食管癌淋巴结转移的相对风险度及其95%可信区间。结果:ALDH2 rs671 G>A3种多态基因型GG,GA,AA在食管癌淋巴结转移组和无淋巴结转移组的频率分别为58.8%(GG),38.8%(GA),2.4%(AA)和59.3%(GG),37.4%(GA),3.3%(AA)(χ2=0.237,P=0.888);以ALDH2 rs671 GG基因型作参照,ALDH2 rs671 AA基因型食管癌淋巴结转移发生的风险降低(调整年龄、性别、吸烟及饮酒状态OR=0.70,95%CI=0.14～3.45),但相关性未达到明显统计学意义。ADH1B rs1229984 A>G3种多态基因型AA,AG,GG在食管癌淋巴结转移组和无淋巴结转移组的频率分别为38.8%(AA),50.6%(AG),10.6%(GG)和42.8%(AA),41.6%(AG),15.6%(GG)(χ2=2.553,P=0.279),以ADH1B rs1229984 AA基因型作参照,ADH1B rs1229984 GG基因型食管癌淋巴结转移发生的风险降低(调整年龄、性别、吸烟及饮酒状态OR=0.66,95%CI=0.29～1.53),但相关性未达到明显统计学意义。结论:ALDH2 rs671G>A和ADH1B rs1229984 A>G基因多态性可能与食管癌淋巴结转移的风险无明显相关,需进一步研究证实。

Alcohol dehydrogenase coexisted solid-state electrochemiluminescence biosensor for detection of p53 gene

An alcohol dehydrogenase （ADH）-coexisted solidstate electrochemiluminescence （ECL） biosensor for sensitive detection of the p53 gene was developed. The electrode modified by multiwalled carbon nanotubes, Ru（bpy）]2＋3 and polypyrrole （ MWNTs-Ru （bpy） ]2＋3 -PPy ） was prepared to adsorb the ssDNA by electrostatic interactions. Then, the ssDNA recognized the gold nanoparticles （AuNPs）-labeled p53 gene and produced the AuNPs-dsDNA electrode with the AuNPs layer. The AuNPs layer adsorbed the ADH molecules for producing the ECL signal. Thus, the biosensor was based on coupling enzyme substrate reaction with solid-state ECL detection, and it displayed good sensitivity and specificity. The detection limit of the wild type p53 sequence （wtp53） is as low as 0. 1 pmol/L and the discrimination is up to 57. 1% between the wtp53 and the muted type p53 sequence （mtp53）. The amenability of this method to the analyses of p53 from normal and cancer cell lysates is demonstrated. The signal of wtp53 in the MGC-803 gastric cancer cell lysates turns out to be about 61.8% that of the wtp53 in the GES-1 normal gastric mucosal cell lysates, and the concentration of the wtp53 is found to decrease about 59 times. The method is highly complementary to enzyme-linked immunosorbent assay （ELISA）, and it holds promise for the diagnosis and management of cancer.

ADH1B和ALDH2基因多态性与相关疾病研究进展

乙醇脱氢酶(ADH)和乙醛脱氢酶(ALDH)是人体肝脏内乙醇代谢的关键酶,共同构成ADH氧化体系。ADH1B和ALDH2分别是ADH和ALDH的2个重要亚型。ADH1B和ALDH2基因多态性与多种疾病,如消化系统疾病、神经退行性变及代谢性疾病等相关。文章对ADH1B及ALDH2基因多态性与相关疾病的关系进行综述,以期为疾病的预防和诊断提供新的思路。

高分辨熔解曲线分析技术检测ALDH2和ADH1B基因多态性

目的建立高分辨率熔解曲线分析体系检测乙醛脱氢酶-2(ALDH2)和乙醇脱氢酶-1B(ADH1B)基因多态性。方法针对ALDH2和ADH1B基因序列设计短片段引物,在核酸扩增后,使用Eva Green染料分析不同聚合酶链反应(PCR)产物,并与Sanger测序法相比较。结果采用高分辨熔解曲线(HRM)法在同一程序下,90min内即可成功检测出ALDH2rs671和ADH1Brs1229984各种基因型,且其结果与Sanger测序一致。结论采用HRM法检测ALDH2和ADH1B基因多态性快速简单、经济有效,值得推广。

Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China

AIM＂ TO evaluate the impact of alcohol dehydrogenase 2 （ADH2） and aldehyde dehydrogenase 2 （ALDH2） polymorphisms on esophageal cancer risk. METHODS;One hundred and ninety-one esophageal cancer patients and 198 healthy controls from Yanting County were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase-chain-reaction with the confronting-two-pair-primer （PCR-CTPP） method. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （95% CI）. RESULTS; Both ADH2＊1 allele and ALDH2＊1/＊2 allele showed an increased risk of developing esophageal cancer. The adjusted OR （95% CI） for ADH2＊1 allele compared with ADH2＊2/＊2 was 1.65 （95% CI = 1.02-2.68） and 1.67 （95% CI = 1.02-2.72） for ALDH2＊1/＊2 compared with ALDH2＊1/＊1. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk, the OR was 1.83 （95% CI = 1.13-2.95）. Furthermore, when compared with ADH2＊2/＊2 and ALDH2＊1/＊1 carriers, ADH2＊1 and ALDH2＊2 carriers showed an elevated risk of developing esophageal cancer among non-alcohol drinkers

ADH2、ALDH2基因多态性及饮酒与胃癌发生的相关性

目的探讨乙醇脱氢酶2(ADH2)、乙醛脱氢酶2(ALDH2)基因多态性及饮酒与胃癌发生的相关性。方法选取原发性胃癌男性患者256例作为观察组,另选取同期进行体检的健康人群100例作为对照组,统计所有研究对象的一般人口学资料及是否吸烟、饮酒,应用基因芯片技术检测ADH2、ALDH2基因多态性,对ADH2和ALDH2基因多态性及饮酒总量与胃癌易感性进行相关性分析。结果 2组文化程度、职业、近10年人均年收入≤4 000元患者比例比较差异均有统计学意义(P均<0.05)。2组ADH2和ALDH2各基因型频率分布比较差异无统计学意义(P>0.05)。与同时携带ADH2 A/A和ALDH2 G/G不饮酒者比较,携带各种ADH2和ALDH2基因型组合者无论是否饮酒及饮酒量多少,胃癌患病风险均无明显增加。结论 ADH2、ALDH2基因多态性及饮酒与胃癌发生并无明显相关性。

Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk:A meta-analysis

AIM:To evaluate the contribution of alcohol dehydrogenase-1B(ADH1B)and aldehyde dehydrogenase-2 (ALDH2)polymorphisms to the risk of esophageal cancer.METHODS:Nineteen articles were included by searching MEDLINE,EMBASE and the Chinese Biomedical Database,13 on ADH1B and 18 on ALDH2.We performed a meta-analysis of case-control studies including 13 studies on ADH1B(cases/controls:2390/7100)and 18 studies on ALDH2(2631/6030).RESULTS:The crude odds ratio[OR(95%confidence interval)]was 2.91(2.04-4.14)for ADH1B*1/*1(vs ADH1B*2/*2)and 1.32(1.17-1.49)for ADH1B*1/*2.The crude OR for ALDH2*1/*2(vs ALDH2*1/*1)was 2.52(1.76-3.61).ADH1B*1/*1 increased the risk of esophageal cancer among never/rare[1.56(0.93-2.61)],moderate[2.71(1.37-5.35)],and heavy drinkers[3.22 (2.27-4.57)].ADH1B*1/*2 was associated with a modest risk among moderate drinkers[1.43(1.09-1.87)].ALDH2*1/*2 increased the risk among never/rare[1.28 (0.91-1.80)],moderate[3.12(1.95-5.01)],and heavy [7.12(4.67-10.86)]drinkers,and among ex-drinkers [5.64(1.57-20.25)].ALDH2*2/*2 increased the risk among drinkers[4.42(1.72-11.36)].ADH1B*1/*1 plus ALDH2*1/*2 was associated with the highest risk for heavy drinkers[12.45(2.9-53.46)].The results of the meta-regression analysis showed that the effects of ADH1B*1/*1 and ALDH2*1/*2 increased with the level of alcohol consumption.ALDH2*1/*2 was associated with a high risk among Taiwan Chinese and Japanese drinkers,as opposed to a moderate risk among drinkers in high-incidence regions of China's Mainland.ADH1B*1/*1 in heavy drinkers and ALDH2*1/*2 in moderate-toheavy drinkers was associated with similarly high risk among both men and women.CONCLUSION:ADH1B/ALDH2 genotypes affect the risk of esophageal cancer,and the risk is modified by alcohol consumption,ethnicity,and gender.

Effects of ADH1C, ALDH2, and CYP2A6 Polymorphisms on Individual Risk of Tobacco-Related Lung Cancer in Male Japanese Smokers

Recent genome-wide association studies have identified several lung cancer susceptibility loci. We previously carried out a replication study in male Japanese smokers that focused on chromosome 5p15 (telomerase reverse transcriptase) and 3q28 (tumor protein p63) (Shimizu et al., Journal of Cancer Therapy, Vol. 2, No. 5, 2011, pp. 690-696). The current study was performed to confirm the association of traditional susceptibility loci [i.e., alcohol dehydrogenase 1C (ADH1C) and aldehyde dehydrogenase 2 (ALDH2)] in 1039 male Japanese smokers (573 lung cancer patients and 466 healthy control subjects) who were previously enrolled in a study to investigate the low odds ratio for lung cancer risk associated with functionally impaired and deletion polymorphisms in cytochrome P450 2A6 (CYP2A6). The minor allele frequency of rs671 in ALDH2 (0.304) was significantly higher in lung cancer cases than in controls (0.226), with an odds ratio of 1.42 [95% confidence interval (CI) of 1.12 - 1.80, p = 0.0033]. No significant association of rs698 in ADH1C with lung cancer risk was found in this population of male Japanese smokers. For light smokers categorized according to the 50th percentile Brinkman index value among the control subjects (620 daily cigarettes × years) and for the CYP2A6*1 wild-type non-carrier sub-population, significantly high odds ratios of 1.98 and 1.68 (95% CI of 1.28 - 3.06, p = 0.0022, and 1.07 - 2.66, p = 0.025), respectively, were observed for rs671 in ALDH2. The present results support the association of ALDH2 loci with lung cancers and suggest a specific effect of ALDH2 loci resulting in a higher risk of lung cancer in light smokers. CYP2A6 polymorphisms, including copy number polymorphisms, may lower the risk of heavy tobacco use-related lung cancer.

Genetic Polymorphisms in ADH1B and ALDH2 Are Associated with Colorectal Tumors in Japan: A Case-Control Study

Background: Unlike with esophageal cancer, acetaldehyde levels and genetic polymorphisms in alcohol dehydrogenase have not yet been shown to be contributing factors for colorectal cancer (CRC). This study aimed to clarify the mechanism of CRC development related to alcohol consumption and to the presence of genetic polymorphisms in the alcohol dehydrogenase, ADH1B and aldehyde dehydrogenase, ALDH2. Methods: This was a case-control study (221 cases and 179 controls) in patients with adenomas and intramucosal tumors who underwent endoscopic removal of all tumors. The amount of alcohol consumption was determined using a self-recorded questionnaire, and the tumor information was obtained from colonoscopy results. Blood samples were taken to analyze the following polymorphisms: ALDH2 Glu504Lys and ADH1B His48Arg. Results: The polymorphisms in ADH1B and ALDH2 had little influence on the development of colorectal adenoma or intramucosal cancer. Patients with ALDH2 (Glu/Glu) were more tolerant of alcohol than those with ALDH2 (Glu/Lys and Lys/Lys). Next, we examined certain combinations of the ADH1B genotypes. In the ALDH2 (Glu/Glu) group, an increased risk (OR = 3.4;95% CI 1.4 - 8.4;P = 0.009) was observed among moderate/heavy drinkers with ADH1B (His/His). In the ALDH2 (Glu/Lys and Lys/Lys) group, an increased risk (OR = 4.2;95% CI 1.1 - 16.7;P = 0.041) was found among moderate/heavy drinkers with ADH1B (Arg/His and Arg/Arg). Conclusions: ADH1B and ALDH2 activity may be involved in the development of CRC.

乙醛脱氢酶2基因多态性和饮酒习惯与肝癌的易感性

目的 研究乙醛脱氢酶 2 (ALDH2 )基因多态性和饮酒习惯与肝癌的易感性关系。方法 在肝癌高发区江苏省泰兴市采用病例对照研究方法 ,病例为确诊的原发性肝癌 (2 0 8例 )新发病例 ,对照 (2 0 8例 )按 1∶1配对 ,选取与病例同性别、年龄相差不超过 2岁 ,与病例居住同村或同一街道的非肿瘤居民 ,调查了研究对象的饮酒习惯等因素 ,并采用聚合酶链反应 限制性片段长度多态性 (PCR PFLP)方法检测了他们的ALDH2基因型。结果 (1)肝癌组中的ALDH2 1 1、ALDH2 1 2 、ALDH2 2 2 基因型频率分别为 5 7.6 9%、30 .77%、11.5 4 % ,与对照组的 6 4 .2 5 %、2 8.5 0 %、7.2 5 %相比 ,差异无显著性 (χ2 =2 .6 4 ,P =0 .2 6 7)。 (2 )携带ALDH2变异基因型 (ALDH2 1 2 或ALDH2 2 2 )的饮酒者与携带ALDH2野生 (ALDH2 1 1)基因型的不饮者相比 ,若开始饮酒年龄 <2 5岁、每月饮酒量 >30 0 0 g、饮酒年数 >2 3年和饮酒总量 >3千克年时 ,前者患肝癌的危险性分别是后者的 3.6 2 (95 %CI=1.2 3～ 10 .70 )、3.5 1(95 %CI=1.38～ 8.95 )、3.0 2 (95 %CI =1.18～ 7.71)和 3.30 (95 %CI =1.2 3～ 8.83)倍。 (3)携带ALDH2变异基因型的饮酒者 ,患肝癌的OR值与饮酒总量存在显著的剂量效应趋势 (P值 =0 .0 4 4 )。(4)HBsAg阳性并携?

乙醛脱氢酶2基因多态性和饮酒习惯与肝癌、胃癌、食管癌的易感性

[目的]研究乙醛脱氢酶2(ALDH2)基因多态性和饮酒习惯与肝癌、胃癌和食管癌的易感性。[方法]88例肝癌以性别、年龄和居住地与对照按1∶1配对 ;104例胃癌和98例食管癌选择同一组(235例)非肿瘤居民为对照 ,用PCR RFLP方法检测研究对象的ALDH2基因型。[结果]肝癌、胃癌、食管癌病例与对照组中ALDH2变异基因型携带者分别占36.36%和35.23%、47.12%和45.36%、32.65%和45.36% ,差异无显著性。在携带ALDH2变异基因型的饮酒人中 ,每月饮酒总量>3kg者发生肝癌的危险性是≤3kg者的7.2倍 ,并存在显著的剂量效应关系。在携带ALDH2谷氨酸纯合型的男性中 ,饮酒者发生癌的危险性是不饮酒者的2.69倍。

江苏汉族人乙醛脱氢酶2基因型分布及其与饮酒习惯的关系

目的 :研究乙醛脱氢酶 2 (ALDH2 )基因多态性在江苏汉族人中的分布频率及其与饮酒习惯的关系。方法 :在江苏泰兴市选择 2 73例正常人进行流行病学调查研究 ,并应用聚合酶链反应 限制性片段长度的多态性 (PCR RFLP)方法检测研究对象的ALDH2基因型。结果 :ALDH2变异型等位基因在中国人中的分布频率为 47.2 5 %。ALDH2变异型等位基因携带者与ALDH2正常等位基因携带者之间饮酒频度和每次饮酒量间差异均无显著性。结论 :中国人ALDH2酶的活性普遍缺乏。人们的饮酒习惯与ALDH2基因型分布无明显的相关关系。