Single Nucleotide Polymorphisms of ADH1B,ADH1C and ALDH2 Genes in 235 People Living in Thai Nguyen Province of Vietnam

Objective: ADH1B, ADH1C and ALDH2 genes are mainly responsible for alcohol metabolism in the body. Severalsingle nucleotide polymorphisms (SNPs) of these genes have been reported to be associated with alcohol dependenceand are considered risk factors for various human diseases. This study aims to identify the prevalence of three SNPs ofADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) in 235 unrelated individuals living in Thai Nguyen province,the northeast region of Vietnam. Methods: The target genotypes were identified by using PCR direct sequencing, andtheir frequencies were compared to previous reports. Result: Our data showed that allele frequencies of ADH1B*2(rs1229984), ADH1C*2 C (rs698) and ALDH2*2 (rs671) were 68.8%, 8.3% and 20.4%, respectively. The ADH1B*2and ADH1C*2 frequencies were similar to those of the Kinh ethnic individuals living in the south region of Vietnam,while the ALDH2*2 frequency was higher. Compared to data from other countries, ADH1B*2 frequency is similar tothe Philippines (60.5%) and Mongolia (62.9%) but significantly different from the other populations. The ADH1C*2frequency is not so different compared to Japanese (5.7%) and Chinese (7.1%) but is quite different in other populations.ALDH2*2 frequency was lower than Japanese (29.3%), Indonesian (30%) and higher than other countries. Regardingthe risk of alcoholism, the percentage of Vietnamese people in this study with genotypes related to alcohol dependenceis 8.1%. In contrast, the carrier has genotypes protecting against alcoholism with high frequency, 91.9%. Among them,the individuals can cause high acetaldehyde accumulation accounting for 33.2%. Conclusion: This study helps tounderstand the genetic polymorphisms of alcohol metabolism genes in the community living in Thai Nguyen province,northeast of Vietnam, and provides valuable scientific data relating to alcohol consumption behavior as well as publichealth protection.     

Alcohol Dehydrogenase-2 and Aldehyde Dehydrogenase-2 Genotypes,Alcohol Drinking and the Risk for Stomach Cancer in Chinese Males

Objective: To investigate the relationship among alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genetic polymorphisms, alcohol consumption, and the susceptibility of stomach cancer in Chinese males. Methods: Three hundred and eighty-two stomach cancer patients and 382 healthy controls from Taixing and Changshu city of Jiangsu province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by PCR and denaturing high-performance liquid chromatography (DHPLC). Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (95% CI). Results: (1) In no drinkers, compared with ALDH2G/G carriers, ALDH2 G/A (OR=1.67, 95%CI: 1.01-2.78) carriers showed a significantly elevated risk of developing stomach cancer. No association was found between ADH2 genotypes and risk of stomach cancer. (2) ALDH2 A allele carriers with cumulative amount of alcohol consumption ≥2.5 (Kg * years) were at a higher risk of developing stomach cancer compared with those with cumulative amount of alcohol consumption <2.5Kg (Kg * years) (OR=2.72, 95%CI:0.89-8.31) and ALDH2 G/G carriers with cumulative amount of alcohol consumption <2.5 (Kg * years) (OR=2.46, 95%CI=0.90-6.72) or ≥2.5 (Kg * years) (OR=2.53, 95%CI=0.86-7.49). (3) Compared with individuals with ADH2 A/A and ALDH2 G/G genotypes, ADH2 G and ALDH2 A allele carriers were not at a high risk of developing stomach cancer, with regard to the status of alcohol consumption, and even cumulative amount of alcohol consumption ≥1.5 (Kg * years) (OR =1.65, 95%CI:0.56-4.82). Conclusion: ADH2 and ALDH2 polymorphisms and alcohol drinking may not play an important role in the development of stomach cancer in Chinese males.     

Esophageal squamous cell carcinoma and ALDH2 and ADH1B polymorphisms in Chinese females

Aim: Alcohol dehydrogenase-IB (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) are the key enzymes for elimination of ethanol and acetaldehyde, the latter being an established animal carcinogen produced after drinking. In this study, we aimed to evaluate the contribution of ADH1B and ALDH2 polymorphisms to the risk of esophageal squamous cell (ESCC) in Chinese females. Methods: A total of 81 pathologically-proven female ESCC cases and 162 female controls were recruited from the Affiliated Hospital of Medical College of Armed Police Forces of PRC in China. ADH1B and ALDH2 polymorphisms were genotyped using PCR-CTPP. Results: Compared with those with ADH1B*2/*2, individuals with ADH2*1/*2 and ADH2*1/*1 had 1.47 and 2.36-fold, respectively, increased risk of developing ESCC (95%CI=0.84-2.58, 95%CI=1.14-5.79) after adjusting for alcohol consumption and other covariates. Significantly increased risk was also noted among subjects with ALDH2*1/*2 (adjusted OR=3.24, 95%CI=1.45-5.36), when compared to those with ALDH2*1/*1. Risk was greater in heavy drinking females carrying ADH1B *1/*1 or ALDH2*1/*2 genotypes compared to those with ADH1B*2 and ALDH2*1/*1. Moreover, we found a significant trend of ESCC risk with alcoholic consumption in women with ALDH2*1/*2. Conclusion: Chinese women with ADH1B *1/*1 or ALDH2*1/*2 have elevated risk of ESCC similarly to men. Women with inactive ADH1B and ALDH2 should reduce drinking and increase their intake of vegetable and fruit to prevent development of esophageal cancer.     

Helicobacter Pylori Seropositivity,the Interleukin 1B Polymorphism,and Smoking among First-visit Outpatients

Our previous studies of 241 re-visit outpatients in the Helicobacter pylori (HP) eradication program (HPE) ofAichi Cancer Center Hospital (Jpn J Cancer Res 2001;92:383-389 ) and of 462 health checkup examinees (HCE) inNagoya (Jpn J Public Health 2001;48:604-612) found a significant association between HP seropositivity and theInterleukin 1B (IL-1B) C-31T genotype, especially among current smokers. This study aimed to confirm the associationfor 547 first-visit outpatients (277 males and 270 females) of Aichi Cancer Center Hospital aged 40 to 79 years.Samples were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP), the samemethod as that used in the previous studies. Sex-age-adjusted odds ratio (aOR) was 1.32 (95% confidence interval,0.84-2.08) for CT genotype and 1.35 (0.84-2.08) for TT genotype. The aOR was higher in never smokers (aOR=1.69,0.86-3.32 for TT genotype) than in current smokers (aOR=1.01, 0.34-2.98 for TT genotype). The obtained aORs forTT genotype were inconsistent to those in our previous studies; aOR=2.46 (1.06-5.74) for 241 HPE, aOR=1.74 (1.05-2.89) for 462 HCE, aOR=22.9 (1.97-266) for 55 HPE current smokers, and aOR=4.62 (0.94-22.7) for 67 HCE currentsmokers. Since the 95% confidence intervals of aORs for TT genotype from the three study subjects overlapped, theinconsistent findings could be due to random errors. Alternatively, there might be other effect modifiers for theassociation with the polymorphism. Further studies will be required to elucidate the causes of the observed inconsistentfindings.     

Allele Frequencies of 25 Polymorphisms Pertaining to Cancer Risk for Japanese,Koreans, and Chinese

Allele frequencies are rather constant among different ethnic groups in many genetic polymorphisms, but some ‍polymorphisms vary in the allele frequency depending on the time when the germ-line base exchanges occurred in ‍the history of humans and on the adaptability of the phenotypes to given environment. This review documented the ‍allele frequencies of polymorphisms pertaining to cancer risk for Japanese, Koreans, and Chinese. Twenty-five ‍polymorphisms of 21 genes whose allele frequencies were available for at least two out of the three ethnic groups ‍were selected. They were ALDH2 Glu487Lys, COMT Val158Met, CYP1A1 MspI and Val/Ile, CYP1B1 Leu432Val, ‍CYP2E1 RsaI, CYP17 T-34C, ER C975G, GSTM1, GSTT1, GSTP1 Ile105Val, IL-1B C-511T, IL-1RN 86-bp VNTR ‍(variable number of tandem repeats), MTHFR C677T and A1298C, NAT1, NAT2, NQO1 Pro187Ser, OGG1 Ser326Cys, ‍p21 Ser31Arg, p53 Arg72Pro, TNF-A G-308A and G-238A, and XRCC1 Arg194Trp and Arg399Gln. The allele ‍frequencies were found for 24 in Japanese, 16 in Koreans, and 24 in Chinese. All of the polymorphisms had similar ‍allele frequencies for these ethnic groups, except the following polymorphisms; ALDH2 Glu487Lys whose Lys allele ‍was more common for Japanese and Taiwanese, COMT Val158Met whose Met allele was more common for Japanese, ‍and NAT2 rapid/slow whose slow alleles were more common for Chinese. When compared with the allele frequencies ‍among Caucasians, the following minor alleles were more frequent among Japanese/Koreans/Chinese; ALDH2 478Lys, ‍CYP1A1 m1 and m2, CYP2E1 c2, ER 975G, GSTT1 null, NAT1 *10, NQO1 187Ser, OGG1 326Cys, p21 31Arg, and ‍XRCC1 194Trp, and less frequent in COMT 158Met, GST-P1 105Val, IL-1RN non-4R, MTHFR 1298C, and TNF-A - ‍308A. The differences in genetic background may affect the impact on the lifestyle factors and/or genotypes examined ‍in epidemiological studies. However, the influences of the variations in the allele frequency seemed to be limited ‍among Japanese, Koreans, and Chinese. The substantial differences in the allele frequency from Caucasians could ‍modify the influences of lifestyle factors and polymorphism genotypes, resulting in the inconsistent results of ‍epidemiologic studies. ‍     

Lack of Association Between CYP1A1 Polymorphisms and Risk of Bladder Cancer: a Meta-analysis

Background: The effects of CYP1A1 gene polymorphisms on the risk of bladder cancer (BC) remaincontroversial. We carried out a meta-analysis to clarify the role of CYP1A1 gene polymorphisms in BC. Materialand Methods: A comprehensive literature search was conducted up to November 20, 2013. Odds ratios (ORs) with95% confidence intervals (CIs) were used to estimate the strength of the association. Meta-regression, subgroupanalysis, sensitivity analysis and publication bias were also performed. Results: Eight studies involving 1,059BC cases and 1,061 controls were included. The meta-analysis showed that there was no significant associationbetween the two common mutations of CYP1A1 and BC risk. For the I1e462Val A/G polymorphism with GG vs.AA the OR was 1.47 (95 % CI= 0.70-3.07, P =0.308). For the MspI T/C polymorphism, though a slight trend wasfound this was not statistically nonsignificant (CC vs.TT, OR = 1.24, 95 % CI= 0.98-1.58, P =0.078). Subgroupanalyses by ethnicity also found no obvious association between CYP1A1 and BC risk. Conclusion: The presentmeta-analysis suggests that CYP1A1 polymorphism is not associated with bladder cancer risk.     

乙醇脱氢酶2基因多态性与食管癌发病风险的Meta分析

目的探讨乙醇脱氢酶2基因多态性与食管癌发病风险的关系。方法检索PubMed和CNKI、万方、维普等数据库,收集相关文献进行Meta分析。以病例组和对照组ADH2基因型分布的比值比（OR）为效应指标,对文献进行评价筛选、异质性检验,应用RevMan5对各研究原始数据进行统计分析。结果最终纳入系统评价进行 Meta 分析的共有9个病例对照研究,其中食管癌患者1 419例,对照2 776例。Meta分析结果为*1/*1vs.*1/*2+*2/*2的合并OR值（95%CI）为2.83(1.89~4.26);*2/*1vs.*2/*2的合并OR值（95%CI）为1.57(1.31~1.88);*1/*1vs.*2/*2的合并OR值（95%CI）为3.31(1.97~5.59)。结论ADH2基因多态性与食管癌易感性之间存在相关,即携带等位基因*1的饮酒者发生食管癌的危险性会增加。     

Prognostic Significance of HER-2/neu and Survival of Breast Cancer Patients Attending a Specialized Breast Clinic in Kolkata,Eastern India

Introduction: The worldwide incidence of breast cancer has increased rapidly in recent years. The scenarioof Eastern India is also showing the same trend. It is necessary to study the utility of HER-2/neu as a prognosticfactor in breast cancer survival. However, there have not been detailed studies in this respect with the breastcancer patients of Eastern India. Thus this study was conducted. Materials and Methods: In this hospital-basedstudy 86 breast cancer patients attending a breast clinic of a reputed institute of Eastern India and having invasiveductal carcinomas were observed for a period of 5 years after surgery. Associations between 5 years observedsurvival and status of ER, PR and HER-2/neu of the patients were critically evaluated. Results: There wasstatistically significant association between survival pattern for 5 years and the HER-2/neu status (p=0.00001).Better survival was observed for the patients with HER-2/neu negative tumors 67(100%) compared to HER-2/neupositive tumors 7(36.8%). Conclusion: There is strong interaction between survival and HER-2/neu expressionof breast cancer patients. Thus the patients with HER-2/neu positive tumors need to be treated aggressively.     

Gene-environment Interactions and Polymorphism Studies for Cancer Risk in Hospital-based Epidemiologic Research Program at Aichi Cancer Center II (HERPACC-II)

Genetic polymorphisms may modify the effects of environmental risk factors on cancer occurence. We have recentlylaunched a comprehensive epidemiologic project, HERPACC II (Hospital-based Epidemiologic Research Programat Aichi Cancer Center II), including both lifestyle and polymorphism data, following HERPACC-I which solelyconcentrated on lifestyle data. As of April 2001, about 3000 samples of DNA are being stored to conduct case-controlstudies. Genotyping of 46 polymorphisms has been conducted at the laboratory of the Division of Epidemiology andPrevention. Twelve case-control studies and two papers on a new PCR method, PCR-CTPP (polymerase chain reactionwith confronting two-pair primers), have been accepted for publication. Significant findings in Japanese were foundfor 1) gene-environment interaction for esophageal cancer between heavy drinking and aldehyde dehydrogenase 2(ALDH2), 2) malignant lymphoma risk with methylenetetrahydrofalate reductase (MTHFR) and methionine synthase(MS), 3) interactions between smoking and two polymorphisms, interleukin 1B (IL-1B) and myeloperoxidase (MPO)for Helicobacter pylori infection, and 4) smoking habits with dopamine receptor D2 (DRD2) and IL-1B. Furtherstudies on interactions with polymorphisms will continue to be conducted for Japanese, using larger sizes of samples.     

Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1⁺ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1⁺ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1^- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1⁺ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma.     

Induction of Apoptosis in Tumor Cells by Natural Phenolic Compounds

Investigation has been conducted to delineate the action of some phenolic compounds of natural origin in fourhuman tumor cell lines: acute myeloblastic leukemia (HL-60), chronic myelogenic leukemia (K-562), breastadenocarcinoma (MCF-7) and cervical epithelial carcinoma (HeLa). In cells grown in appropriate media the phenolicscurcumin, yakuchinone B, resveratrol and capsaicin exhibited growth inhibition as assessed by trypan blue dyeexclusion. It was evident from the results of the MTT reduction assay and [3H]thymidine incorporation into nuclearDNA that the phenolics were cytotoxic and inhibited cell proliferation. Dose response studies indicated curcumin tobe most cytotoxic towards HL-60, K-562 and MCF-7 but did not show much activity in HeLa cells. On the otherhand, yakuchinone B, although less active than curcumin, displayed cytotoxicity towards all four cell lines. Resveratrolwas cytotoxic only in leukemic cells, while capsaicin was marginally cytotoxic. All these phenolics did not elicit anycytotoxic activity as judged by the above parameters towards lymphocytes purified from normal human blood.When cells treated with phenolics were stained with propidium iodide and examined under a fluorescent microscope,characteristic apoptotic features such as chromatin condensation and nuclear fragmentation were observed. Scoringof cells with apoptotic and non-apoptotic features showed positive correlation of apoptotic index with dose of phenolic,and fragmented DNA extracted free of genomic DNA displayed on gel electrophoresis a typical ladder pattern.These phenolics which have human exposure are known cancer chemopreventive agents and their action as inducersof apoptosis in tumor cells suggest their potential use in a strategy for cancer control.     

乙醇和乙醛脱氢酶基因多态与男性结直肠癌的易感性

目的研究乙醇脱氢酶2(ADH2)和乙醛脱氢酶2(ALDH2)基因多态及饮酒习惯与男性结直肠癌易感性的关系。方法在江苏省进行了一项病例-对照研究(结直肠癌患者190例,人群对照222名),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用聚合酶链反应(PCR)和变性高效液相色谱法(DHPLC)检测研究对象的ADH2Arg47His(G-A)和ALDH2Glu487Lys(G-A)的基因型。结果①ADH2A/A和ALDH2G/G基因型显著增加结直肠癌的易感性。在调整了年龄和吸烟状况后,ADH2A/A基因型者与携带G等位基因者相比,发生结直肠癌的危险性上升到1.61(95%CI:1.09~2.38);ALDH2G/G基因型者与携带A等位基因者相比,发生结直肠癌的危险性上升到1.79(95%CI:1.19~2.69)。②与ADH2G和ALDH2A等位基因携带者相比,同时携带ADH2A/A和ALDH2G/G基因型者发生结直肠癌的OR值上升到3.05(95%CI:1.67~5.57);与不饮酒的ADH2G等位基因携带者相比,拥有ADH2A/A基因型的饮酒者的OR值上升到3.44(95%CI:1.84~6.42);与不饮酒的ALDH2A等位基因携带者相比,拥有AL-DH2G/G基因型的饮酒者的OR值上升到2.70(95%CI:1.57~4.66)。结论ADH2和ALDH2基因多态性与男性结直肠癌的易感性相关。ADH2,ALDH2基因多态之间以及基因多态与饮酒习惯之间,在结直肠癌发生中存在显著的协同作用。     

Associations between a PTPN11 Polymorphism and Gastric Atrophy - Opposite in Uzbekistan to that in Japan

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of gastric epithelial cells interacts with cagA from Helicobacter pylori (H. pylori). Our previous studies found the AA genotype of a G/A single nucleotide polymorphism at intron 3 (rs2301756) of PTPN11 gene, which encodes SHP-2, to be associated with a lower risk of gastric atrophy. The present study aimed to examine the association with gastric atrophy among the subjects of a case-control study of peptic ulcer disease (PUD) conducted in the Uzbek Republic. Cases were 95 patients (61 males and 34 females) with PUD aged 16 to 85 years. Controls were 102 hospital volunteers (42 males and 60 females) including 42 patients with miscellaneous diseases, aged 15 to 75 years. Gastric atrophy was evaluated with serum pepsinogens (PG1<70ng/ml and PG1/PG2<3). Polymorphisms of PTPN11 at intron 3 (rs2301756) and intron10 (rs12229892) were genotyped with PCR with confronting two-pair primers (PCR-CTPP). Anti-cagA IgG antibody was detected in 93.7% of cases and 77.5% in controls. Gastric atrophy was observed in 24.2% of the PUD patients and 33.3% in the controls. The A allele at intron 3 was completely linked to the G allele at intron 10. The age, sex, and group (cases and controls) adjusted odds ratio of gastric atrophy was 0.18 (95% confidence interval, 0.04-0.86) for intron 3 GG genotype relative to AA genotype. Since the finding was opposite to that among Japanese, the H. pylori strains and/or lifestyle in Uzbekistan might modify the association.     

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。结论：该研究揭示了携带ALDH2变异基因型者大量饮酒将显著增加患肝癌的危险性。     

Breast Cancer in Young Women: Prognostic Factors and Clinicopathological Features

Objective:The aim of this study was to determine most significant prognostic factor for overall survival of invasiveduct operable breast cancer from clinical stage, pathological stage, epidemiological, anatomic and cellular andmolecular genetic factors. Materials and Methods: Research design was prospective cohort. Duct invasive operablebreast cancer patients who were diagnosed and treated with standard protocol since 1993, followed prospectivelyuntil November 2003 by clinical stage, pathological stage, age, tumor size, lymph node status, histological grade,mitotic index, ER,PR, c-erbB2, p53 and MIB-1, until revealed outcome (death). Prognostic factor was analyzedunivariately for overall survival with Kaplan Meier method. Difference between two survival group was analyzedwith log- rank test. Independent prognostic factor was analyzed multivariately using proportional hazard (Cox)regression. Results:With univariate analysis, significant prognostic factors for overall survival were clinical stage(p<0.001), pathological stage (p<0.001), tumor size (p<0.001), lymph node status (p<0.001) and adjuvant chemotherapy(p <0.005). Multivariately, most significant prognostic factors for survival were lymph node status (p = 0.001 ; Expβ = 7.775; 95% CI: 2.276 – 26.56) and clinical stage (p = 0.029; Exp β= 2.142; 95% CI: 1.081 – 4.244). Conclusion:Independent prognostic factors for survival are lymph node status and clinical stage.     

C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis

A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420Tpolymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a moreprecise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 availablestudies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significantassociation between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer,gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associatedwith decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838,95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysiswas performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverseassociation was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for thePB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association wasonly found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggestthat SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decreasecancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies willbe necessary to validate the risk identified in the current meta-analysis.     

A Population-based Follow-up Study on Mortality from Cancer or Cardiovascular Disease and Serum Carotenoids,Retinol and Tocopherols in Japanese Inhabitants

Objective: Observational epidemiologic studies have shown that a high intake of dietary and high serum levels ofcarotenoids are associated with a reduced risk of mortality from cancer and cardiovascular disease. To investigatewhether high serum levels of carotenoids can reduce mortality rates, a population-based follow-up study was conductedamong Japanese inhabitants. Materials and Methods: Three thousand two hundred and fifty-four subjects (1,260males and 1,994 females) aged from 39 to 85 years who had attended health check-up programs from 1989 to 1995were recruited from the Japanese population. Serum levels of carotenoids, retinol and tocopherols were separatelydetermined by high-performance liquid chromatography. Hazard ratios for serum values of carotenoids, retinol andtocopherols were estimated by Cox’s proportional hazard model after adjusting for sex, age, and other confoundingfactors. Results: During the 11.7-year follow-up period, 140 deaths (86 males and 54 females) from cancer of all siteswere identified among the cohort subjects, including 41 from lung , 17 from stomach , 16 from colorectal and 12from liver cancer, as well as 89 deaths from cardiovascular disease, including 45 from heart disease and 37 fromstroke. High serum values of carotenoids including xanthophylls were apparently associated with low hazard ratiosfor mortality rates of cancer of all sites or of cardiovascular disease. High serum values of β-carotene, total carotene,provitamin A and total carotenoid for colorectal cancer or stroke also appeared to be related to low hazard ratios.Those of retinol and tocopherols were not associated with any reduction in risk of mortality from cancer orcardiovascular disease. Conclusions: Our follow-up study demonstrated that a typical Japanese diet related to elevatingserum levels of carotenoids with provitamin A activity may significantly reduce risk of mortality from cancer ofcertain sites or cardiovascular disease, especially colorectal cancer or stroke, while high serum levels of somexanthophylls, retinol and tocopherols do not.     

A unique seroepidemiological pattern of HBV,HCV and HTLV-I in Nenets and Komi in Northwestern Russia

An epidemiological study of hepatitis viruses type B (HBV) and type C (HCV) and human T-cell leukemia virus ‍type I (HTLV-I) was carried out among 105 residents (male:female=19:86) regarded as Nenets partly mixed with ‍Komi, in the region of Krasnoe, the Nenets Autonomous District of the Arkhangelsk Region, in northwestern Russia ‍in 2004. Blood was drawn from apparently healthy volunteers at ages of 41.6+16.5 (range 14-85) years. HBsAg, ‍HBsAb, HBcAb, HBeAb and HCV Ab were measured by microparticle enzyme-immunoassay, and HTLV-I Ab was ‍measured by particle agglutination. Prevalences of HBsAg(+), HBsAb(+), HBcAb(+) and HBeAb(+) were 0.0%, ‍29.5.%, 20.0% and 7.6%, respectively. The overall HBV infection rate (positive HBsAb or HBcAb) was 34.3%, ‍while no positive HCV or HTLV-I Abs could be detected. A serological subgroup with positive HBsAb and negative ‍HBcAb, consisting of 15(14.3%) females, contrasted sharply to other serological subgroups in sex, age, parent’s ‍ethnicity, positive HBeAb rate, and HBcAb inhibition%. We conclude that HBV is prevalent with unique serological ‍patterns among the Nenets, while HCV and HTLV-I infections are negligible.     

Magnitude of Arsenic Toxicity in Tube-well Drinking Water in Bangladesh and Its Adverse Effects on Human Health Including Cancer: Evidence from a Review of the Literature

Only after a decade from 1993, arsenic contamination of groundwater in Bangladesh has been reported as the ‍biggest arsenic catastrophe in the world. It is a burning public health issue in this country. More than 50 percent of ‍the total population is estimated at risk of contamination. Already thousands of people have been affected by the ‍disease arsenicosis. Many more may be on the way to manifest lesions in future. We conducted a review of previous ‍studies and published articles including MEDLINE database on this issue. We found that 59 districts out of 64 have ‍been already affected by arsenic in underground drinking water, where this particular source of drinking water is ‍the main source for 97 percent of the rural people. The water is unfortunately now a great threat for the human ‍being due to high level of arsenic. Continuous arsenic exposure can lead people to develop arsenicosis, which in turn ‍elevates the risk of cancer. Skin lesions are the most common manifestations in arsenicosis patients. Relatively poor ‍rural people and other socio-economically disadvantaged groups are more affected by this exposure. Until now ‍cancer patients have been relatively limited in Bangladesh. One of the reasons may be that several years are needed ‍to show cancer manifestations from the beginning of arsenic exposure. But it is suspected that after some years a ‍large number of patients will appear with cancer in different sites for arsenic exposure in drinking water. Various ‍studies have been conducted in arsenic affected countries - notably in Argentina, Chile, China, Japan, and Taiwan - ‍to find the potential of arsenic exposure to cause development of cancer. Among the arsenic related cancers, liver, ‍lung, skin, bladder and kidney cancers are reported to be prevalent in these countries. Unfortunately no scientific ‍study has been yet conducted in Bangladesh to find the relationship between arsenic exposure and cancers in different ‍sites of the body. So our aim is to conduct an ecological as well as a case-control study in the country in the future. ‍     

Minimal Sizes of Cases with a Susceptible Genotype and Minimal Odds Ratios among Susceptible Individuals in Case-control Studies

Objective: Disease risk elevation due to an environmental factor only for individuals with a susceptible genotype ‍is a typical example of gene-environment interaction. In order to identify risk factors interacting with susceptible ‍genotypes in case-control studies, presumptions on minimal size of cases with the susceptible genotype (Smin) and ‍odds ratio (OR) among the susceptible individuals (ORsusceptible) are useful. ‍Model: Proportion of exposed cases (P1) and OR for whole cases (ORwhole) statistically detectable in a case-control ‍study can be calculated in a conventional method. P1 was assumed to be a weighted sum of the exposed among cases ‍with the genotype (Px) and cases without the genotype (equal to proportion of the exposed among controls, P0), i.e., ‍S Px + (1 - S) P0, where S is the size (proportion) of cases with the genotype. For each calculated P1, S became the ‍minimum (Smin) in case of Px = 1. ORsusceptible was calculated by {Px (1 - P0)} / {(1 - Px) P0}. ‍Results: Smin and ORsusceptible were listed for the combinations of the above components. For example, a detectable ‍P1 was 0.638 for P0=0.5 in a case-control study with 200 cases (N1) and 200 controls (N0), when á error of a two-sided ‍test was 0.05 with an 80% of power. In case of P1=0.638, ORwhole was 1.77, producing Smin=0.277 for infinite ORsusceptible. ‍It indicates that an environmental factor cannot be detected in case that a high-risk genotype frequency is less than ‍0.277. ‍Interpretation: If the size of cases with a susceptible genotype is expected to be less than Smin, case-control studies ‍are unlikely to detect a significant OR of the environmental factor.