hOGG1基因多态性与胃癌遗传易感性的关系

目的探讨人类8-羟基鸟嘌呤DNA糖苷酶1（hOGG1）基因多态性与胃癌遗传易感性的关系。方法收集河南郑州和开封地区98例胃癌患者和80例非肿瘤对照组志愿者外周血样,应用聚合酶链反应一限制性片段长度多态性（PCR—RFLP）检测法检测胃癌人群的外周血中DNA损伤修复酶基因多态性,分析其与肿瘤遗传易感性的关系。结果hOGGISer326Cys基因的各基因型频率在胃癌组和对照组间的分布差异有统计学意义（P〈0．05）。携带Cys326Cys基因型者胃癌的发病风险增加1．7倍（OR=I．706,95％CI=0．341～2．462,P=0．002）。hOGGlSer326Cys基因多态性与酒的交互作用增加胃癌的发病风险（S〉1,API=0．38）。结论Cys326Cys基因型是胃癌发病的危险基因型,携带Cys易感基因与饮酒交互作用时可能增加患胃癌的易感性。     

8-羟基鸟嘌呤糖苷酶1基因多态性与喉癌易感性的关系

目的:探讨8-羟基鸟嘌呤糖苷酶1基因(hOGG1)Ser326Cys多态性与喉癌遗传易感性的关系.方法:采用病例-对照设计,选择72例喉鳞状细胞癌患者(病例组),并与72例性别比一致,平均年龄相差＜5岁的对照组进行比较.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析hOGG1c.326多态性.结果:病例组hOGG1c.326杂合型及突变(Ser/Cys Cys/Cys)比例高于对照组(P＜0.05),携带hOGG1c.326Ser/Cys Cys/Cys基因型个体较携带hOGG1c.326Ser/Ser基因型的个体患喉癌的风险升高了2.54倍.结论:hOGG1c.326(Ser/Cys或Cys/Cys)基因型可能是喉癌发病的风险因子,其可作为一种易感性分子标志物,对喉癌的早期预防具有一定的参考价值.     

Genetic polymorphisms in hMTH1, hOGG1 and hMYH and risk of chronic benzene poisoning in a Chinese occupational population

Oxidative damage to DNA induced by benzene is an important mechanism of its genotoxicity, which leads to chronic benzene poisoning (CBP). Therefore, genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population. We hypothesized that single nucleotide polymorphisms (SNPs) in hMTH1, hOGG1 and hMYH genes are associated with risk of CBP. We genotyped SNPs at codon 83 of hMTH1, codon 326 of hOGG1, and codon 324 of hMYH in 152 CBP patients and 152 healthy workers occupationally exposed to benzene without poisoning manifestations. The genotypes were determined by polymerase chain reaction-restrained fragment length polymorphism (PCR-RFLP) technique. There were 2.51-fold [adjusted odds ratio (OR_adj), 2.51; 95% CI, 1.14-5.49; P = 0.02] and 2.49-fold (OR_adj, 2.49; 95% CI: 1.52-4.07; P < 0.01) increased risk of CBP for individuals carrying genotypes of hMTH1 83Val/Met + Met/Met and hOGG1 326Cys/Cys, respectively. Compared with individuals carrying genotypes of hOGG1 326Cys/Cys and hMYH 324His/His at the same time, there was a 0.33-fold (OR_adj, 0.33; 95% CI: 0.15-0.72; P < 0.05) decreased risk of CBP for those with genotypes of hOGG1 326Ser/Cys + Ser/Ser and hMYH 324His/Gln + Gln/Gln. In the smoking group, there was a 0.15-fold (OR_adj, 0.15; 95% CI, 0.03-0.68; P = 0.01) decreased risk of CBP for subjects carrying genotypes of hMYH 324His/Gln + Gln/Gln compared with those of genotype of hMYH 324His/His. Therefore, our results suggested that polymorphisms at codons 83 of hMTH1 and codon 326 of hOGG1 might contribute to CBP in a Chinese occupational population.     

Association of <Emphasis Type="Italic">hOGG1</Emphasis> genotype with life style and oxidative DNA damage among Chinese ethnic populations

To assess the natural variation of hOGG1 gene and the gene–environmental interactions, the hOGG1 codon 326 polymorphism and urinary 8-OHdG levels were investigated in large samples (n = 953) of healthy individuals from five Chinese ethnic populations by using PCR-RFLP and HPLC-ECD. Life-style parameters under study were obtained through a questionnaire. The allelic frequencies of the hOGG1 gene in the Chinese populations were found to be 0.16 (Ser/Ser), 0.49 (Ser/Cys) and 0.35 (Cys/Cys), respectively. The frequencies of Ser326Cys polymorphism were significantly different among the five Chinese ethnic populations (P = 0.002). No association was found between the hOGG1 gene polymorphism and other life-style parameters except for the association between Ser326Cys and smoking (P = 0.027). A significant increase of urinary 8-OHdG level was observed in Cys326Cys allelic healthy subjects (P = 0.033). These results suggest that there are natural variations of hOGG1 gene among Chinese ethnic populations. Smoking relates to Cys/Cys polymorphism frequencies, and oxidative DNA damage is repaired less in individuals with the hOGG1 Cys326Cys genotype.     

Rapid detection of the hOGG1 Ser326Cys polymorphism using LightCycler technology

Human 8-oxoguanine DNA glycosylase 1 (hOGG1) plays an important role in the repair of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodGuo), one of the major constituents in DNA damage. A recent in vitro study showed that the hOGG1 326Cys polymorphism (rs1052133) exhibits reduced 8-oxodGuo repair activity. This study aimed to develop a LightCycler (LC) assay to analyze the C>G polymorphism (Ser326Cys) in exon 7 of the hOGG1 gene followed by validation of the method using DNA samples from 260 polycyclic aromatic hydrocarbons(PAH)-exposed workers with known 8-oxodGuo DNA-adduct values measured by HPLC. Twenty DNA samples were analyzed by a PCR-RFLP analysis with Fnu4H I to generate control DNA. LC melting curve analyses of the hOGG1 exon 7 PCR product were characteristic of the probes hybridized to the non-mutated Ser-type (CC) at 65 degrees C, or to the Cys mutant (GG) at 59 degrees C. The distribution in the population of PAH-exposed workers (N=260) was 58% (CC), 38%(CG), and 4% (GG). The minor G allele displayed a frequency of 23 %. The distribution of 8-oxodGuo adducts for the Ser326Cys variants of hOGG1 revealed geometric means (GM) of 5.83 (CC), 5.27 (CG), and 6.53 (GG) 8-oxodGuo adducts/10(6)dGuo. Corresponding GM values of current smokers were 5.7 (CC), 5.6 (CG) and 7.0 (GG) 8-oxodGuo adducts/10(6) dGuo. The analysis of the Ser326Cys polymorphism in 260 DNA samples with this new LC assay revealed that this method is reliable for high throughput analysis of this key polymorphism in the hOGG1 gene.     

hOGG1 promoter methylation,hOGG1 genetic variants and their interactions for risk of coal-borne arsenicosis: A case-control study

To identify the effect of hOGG1 methylation, Ser326Cys polymorphism and their interactions on the risk of coal-borne arsenicosis, 113 coal-borne arsenicosis subjects and 55 reference subjects were recruited. Urinary arsenic contents were analyzed with ICP-MS. hOGG1 methylation and Ser326Cys polymorphism was measured by mehtylation-specific PCR and restriction fragment length polymorphism PCR in PBLCs, respectively. The results showed that the prevalence of methylated hOGG1 and variation genotype (326 ^Ser/Cys & 326 ^Cys/Cys) were increased with raised levels of urinary arsenic in arsenicosis subjects. Increased prevalence of methylated hOGG1 and variation genotype were associated with raised risk of arsenicosis. Moreover, the results revealed that variant genotype might increase the susceptibility to hOGG1 methylation. The interactions of methylated hOGG1 and variation genotype were also found to contribute to increased risk of arsenicosis. Taken together, hOGG1 hypermethylation, hOGG1 variants and their interactions might be potential biomarkers for evaluating risk of coal-borne arsenicosis.     

The hOGG1 Ser326Cys polymorphism and Huntington's disease

Increasing evidence supports a role for oxidative DNA damage and impaired DNA repair mechanisms in the pathogenesis of age related neurodegenerative diseases. Within this context there is a current interest in the understanding of the role played by polymorphisms of DNA repair genes in the inter-individual risk to develop neurodegenerative pathologies, as well as in the onset and the progression of disease symptoms. Particularly, somatic CAG repeat expansion of the gene encoding for huntingtin has been observed in tissues of patients affected by Huntington's disease (HD), including blood and brain. Recent evidence suggests that somatic CAG repeat expansion in HD cells might contribute to disease age at onset and is mediated by the DNA repair OGG1 enzyme, during the removal of 8-oxoguanine (8-oxoG) from the DNA. There is also evidence that the expression of hMTH1, which removes 8-oxoG from the nucleotide pool, protects mice from HD-like symptoms, and progenitor striatal cells from the toxic effects of the mutant huntingtin. The hOGG1 Ser326Cys polymorphism results in reduced OGG1 activity and increased 8-oxoG formation. In the present study, performed on blood DNA from 91 HD subjects, we observed that bearers of the mutant Cys326 allele (Ser326Cys + Cys326Cys) tend to have an increased number of CAG repeats of the expanded HD allele (P = 0.049); moreover bearers of at least one copy of the mutant Cys326 allele, mainly heterozygous subjects, showed a significant (P = 0.041) earlier disease onset than Ser326Ser wild-type individuals, suggesting a possible role of the hOGG1 Ser326Cys polymorphism in HD phenotype.     

A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking

X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base-excision repair pathway. Functional Polymorphisms in the XRCC1 gene may lead to decreased DNA repair capacity and thus confer inherited predisposition to cancer risk. In this case-control study of 710 patients with incident lung cancer and 710 cancer-free controls who were frequency matched on age, sex and residential area, we genotyped a novel T>C transition at the promoter region (-77T>C) of XRCC1 and other two common non-synonymous polymorphisms (Arg194Trp and Arg399Gln) to determine their associations with risk of lung cancer. We found that compared with the -77TT wild-type homozygote, the variant genotypes were associated with significantly increased risk of lung cancer [adjusted odds ratio (OR)=1.51; 95% confidence interval (CI)=1.17-1.94 for -77TC; OR=2.98; 95% CI=0.93-9.59 for -77CC; and OR=1.55; 95% CI=1.21-1.98 for -77TC/CC]. By contrast, no significant associations were observed between the other two exonic variants (Arg194Trp and Arg399Gln) and lung cancer risk. Furthermore, we observed a 9.82-fold increased risk (95% CI=5.66-17.02) for heavy smokers carrying the -77C variant (-77TC/CC) and a 4.07-fold increased risk (95% CI=2.85-5.81) for heavy smokers not carrying the variant. However, the interaction between the -77T>C variant and cumulative smoking was not statistically significant (P=0.1560). These findings indicate that the new XRCC1 -77T>C polymorphism may contribute to the aetiology of lung cancer. Further functional studies are warranted to elucidate the underlying molecular mechanisms of the association.     

OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility

8-Oxoguanine DNA glycosylase 1 (OGG1) plays an important role in repairing oxidative DNA damage induced by chemical agents, such as tobacco. This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking, alone or combined, on sperm oxidative DNA damage and the risk of male infertility. A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study. Sperm 8-hydroxydeoxyguanine (8-OHdG) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip-based Taq-Man genotyping technology. Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8-OHdG levels. Individuals with variant Cys/Cys homozygote showed higher levels of sperm 8-OHdG than wide-type homozygote carriers (Ser/Ser). Stratified analysis found that the association between OGG1 polymorphism and sperm 8-OHdG levels was only observed among smokers with pack-years ≥5 but not among those subjects with pack-years < 5 (pack-years = packs smoked per day × years as a smoker). Further analysis based on the case–control study revealed that variant allele (Cys) of OGG1 was significantly associated with male infertility risk in a dominant model (OR = 1.35, 95% CI: 1.01–1.82; trend P < 0.001). Furthermore, we found a significant gene–environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk (P_interation = 0.0003). These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk.     

GSTM1基因多态性与满族人群肺癌易感性关系

目的 研究内蒙古地区GSTM1基因多态性与满族人群肺癌易感性关系.方法 采用多重PCR分析技术对内蒙古地区214例正常满族人及128例满族肺癌患者进行GSTM1基因多态性检测,并联合吸烟状况,分析GSTM1基因多态性及吸烟与肺癌之间的相互关系.结果 ①与GSTM1(+)基因型相比,携带GSTM1(-)基因型的个体患肺癌的危险度升高2.264倍;②吸烟人群较不吸烟人群患肺癌的危险度升高2.143倍;③与携带GSTM1(+)的非吸烟者相比,携带GSTM1(-)吸烟者患肺癌的危险度升高,OR值为5.504(95％ CI=2.837～10.676),且结果具有统计学意义(P＜0.001);携带GSTM1(-)的非吸烟者与携带GSTM1(+)的吸烟者患肺癌的危险度均升高,OR值分别为1.546 (95％ CI=0.771～3.100)和1.154(95％ CI=0.572～2.327),但结果没有显著性差异(P＞0.05).结论 GSTM1(-)、吸烟为内蒙古地区满族人群肺癌的易感因素.     

Dose-dependent influence of genetic polymorphisms on DNA damage induced by styrene oxide, ethylene oxide and gamma-radiation

Styrene oxide (SO), ethylene oxide (EO) and gamma-radiation (G) are agents with a well-described metabolism and genotoxicity. EPHX1 and GSTs play an important role in the detoxification of electrophiles and oxidative stress. Enzymes involved in base excision repair (hOGG1, XRCC1), in rejoining single strand breaks (XRCC1) and in repair of cross-links and chromosomal double strand breaks (XRCC3) might have an impact on genotoxicity as well. In this study we assessed the dose-dependent effect of genetic polymorphisms in biotransforming (EPHX (Tyr113/His113 and His139/Arg139), GSTP1 (Ile105/Val105), GSTM1 and GSTT1) and DNA repair enzymes (hOGG1 (Ser326/Cys326), XRCC1 (Arg194/Trp194, Arg280/His280, Arg399/Gln399), XRCC3 (Thr241/Met241)) on the induced genotoxicity. Peripheral blood mononuclear cells from 20 individuals were exposed to 3 doses per agent (+control). Genotoxicity was evaluated by measuring comet tail length (TL) and micronucleus frequencies in binucleated cells (MNCB). Dose-dependent DNA damage was found for all agents and end-points, with the exception of MNCB induced by EO. Repeated measure ANOVA revealed a significant contribution of hOGG1 and XRCC3 genotypes to the inter-individual variability of TL and MNCB in cells exposed to EO and G. Homozygous hOGG1326 wild cells showed significantly lower EO-induced TL than the heterozygous cells. Significantly higher TL and MNCB were found in EO-exposed cells carrying the XRCC3(241)Met variant and the influence on TL was more pronounced at higher dose. In G-irradiated cells, TL was significantly higher in the hOGG1326 homozygous wild types compared with mutated genotypes. The influence of hOGG1326 on TL was borderline dose-dependent. We conclude that the influence of genetic polymorphisms of enzymes involved in DNA repair on induced genotoxicity depends on exposure dose.     

Modulation of oxidative DNA damage by repair enzymes XRCC1 and hOGG1

The influence of DNA repair gene polymorphisms (XRCC1: Arg194Trp, Arg280His, Arg399Gln; APE1: Asp148Glu; hOGG1: Ser326Cys) on oxidative DNA damage is controversial and was investigated in 214 German workers with occupational exposure to vapors and aerosols of bitumen,compared to 87 German construction workers without exposure, who were part of the Human Bitumen Study. Genotypes were determined by real-time polymerase chain reaction (PCR), and actual smoking habits by a questionnaire and cotinine analysis. Oxidative DNA damage in white blood cells (WBC) collected pre- and postshift was measured as 8-oxodGuo adducts/10(6) dGuo by a hjigh-performance liquid chromatography electron capture detection (HPLC-ECD) method, followed by calculation of the difference between post- and preshift values (Δ8-oxodGuo/10(6) dGuo). The 214 bitumen exposed workers showed higher median Δ8-oxodGuo values than the 87 references. In the whole study group (n=301) there was a trend for increasing adduct values for XRCC1 Arg(GG)399Gln(AA) during a shift, especially in nonsmokers (n=108. Referents (n=87) displayed a similar trend for hOGG1 Ser(CC)326Cys(GG). In contrast, XRCC1 Arg(GG)280His(AA) showed a decrease of median Δ8-oxodGuo/10(6) dGuo values in workers with exposure to vapors and aerosols of bitumen (n=214), especially in smokers (n=145). XRCC1 Arg194Trp and APE1 Asp148Glu displayed no marked association with Δ8-oxodGuo levels. Data indicate that the combination of different variants in DNA damage repair enzymes may modulate the production of 8-oxoguanine adducts in WBC produced by xenobiotics during a shift.     

Glutathione S-transferases mu 1, theta 1, pi 1, alpha 1 and mu 3 genetic polymorphisms and the risk of colorectal and gastric cancers in humans

INTRODUCTION: Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. This study aimed to elucidate the influence of several GST polymorphisms on colorectal and gastric cancer risk. PATIENTS AND METHODS: GST mu1 (GSTM1), theta1 (GSTT1), pi1 (GSTP1), alpha1 (GSTA1) and mu3 (GSTM3) genotypes were determined in 144 colorectal cancer patients, 98 gastric cancer patients and 329 healthy control individuals. RESULTS: Colorectal cancer: the risk is greater for carriers of the GSTM1 null genotype (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.25-2.91), for carriers of the GSTT1 null genotype (OR = 3.62, 95% CI = 2.34-5.62), and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 4.98, 95% CI = 2.77-9.00). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.31, 95% CI = 0.09-0.88). Among carriers of the GSTP1 Ile/Ile genotype, smoking increases the risk compared with nonsmoking (OR = 2.35, 95% CI = 1.11-4.99). Gastric cancer: the risk is greater for carriers of the GSTT1 null genotype (OR = 2.58, 95% CI = 1.53-4.36) and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 3.32, 95% CI = 1.62-6.77). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.20, 95% CI = 0.02-0.86). DISCUSSION: The GSTT1 null genotype, particularly if it is associated with the GSTM1 null genotype, greatly increases the risk for colorectal and gastric cancers. The GSTP1 104 Val/Val genotype may protect from both malignant tumors. CONCLUSION: This study indicates that GST polymorphisms, in particular the GSTM1/GSTT1 double-null haplotype, can be considered low-penetrance genes for gastrointestinal cancer.     

Polymorphic trial in oxidative damage of arsenic exposed Vietnamese

Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 Asp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNPs was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes.     

CYP2E1 and NQO1 genotypes,smoking and bladder cancer

BACKGROUND: Cytochrome P450 2E1 (CYP2E1) and NAD(P)H:quinone oxidoreductase (NQO1) catalyze the activation of some environmental procarcinogens present in tobacco smoke (i.e. nitrosoamines and heterocyclic amines). We conducted a hospital based case-control study to evaluate the potential association between genetic polymorphisms of CYP2E1 (C1019T in the 5' flanking region) and NQO1 (C609T in exon 6) and bladder cancer risk in Asian population. METHODS: The study population was comprised of 218 histologically confirmed prevalent bladder cancer cases and 199 controls without cancer or systemic illness. PCR-restriction fragment length polymorphism based methods were used for the genotyping analyses and unconditional logistic regression model for the statistical evaluations. RESULTS: The risk of bladder cancer increased with the amount of smoking (P for trend < 0.01). The frequency of CYP2E1 c1/c1 genotype was significantly higher in bladder cancer patients (57.9%) than in the controls (47.9%) (OR = 1.8, 95% CI = 1.1-2.9). Similarly, the NQO1 C/C genotypes were significantly more prevalent in the patients (45.8%) than in the controls (37.6%) (OR = 1.6, 95% CI = 1.0-2.7). The risk for bladder cancer increased with the number of the putative risk genotypes (P for trend = 0.03); the most remarkable risk was observed for heavy smokers with both CYP2E1 c1/c1 and NQO1 C/C genotypes (OR = 13.8, 95% CI = 3.9-48.6) when compared to non/light smokers with other genotypes. CONCLUSION: Our findings suggest that CYP2E1 and NQO1 genotypes may play an important role in development of smoking related bladder cancer among Korean men.     

Sulfotransferase 1A1 (SULT1A1) polymorphism and breast cancer risk in Chinese women

BACKGROUND: Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, catalyzes the sulfation of a variety of phenolic and estrogenic compounds. A functional polymorphism of the SULT1A1 gene has been implicated in a decreased activity and thermostability when the wild-type arginine (Arg) at codon 213 is substituted by a histidine (His). METHODS: We investigated the association between the His allele and the risk breast cancer in 213 cases and 430 matched controls in Chinese women, and the interaction between His allele and endogenous estrogen and dietary mutagens exposure factors were also determined by use of logistic regression analysis. RESULTS: There was no significant difference in genotypes between the cancer patients and control populations. However, the frequency of the His allele in cases (13.6%) were significant higher than that in controls (9.5%), P = 0.03. Compared with women carrying the Arg/Arg genotype, the adjusted odds ratio (OR) of Arg/His was 1.48 (95% CI = 0.59-3.31) and His/His was 2.28 (95% CI = 0.69-9.58), P trend was 0.04. The adjusted OR of Arg/His + His/His was 2.60 (95% CI = 1.12-6.05). His allele strengthen the effect of endogenous estrogen exposure with interaction index r > 1, and weaken the effect of heterocyclic amines and polycyclic aromatic hydrocarbons derived from dietary with interaction index r > 1, both were multiplicative interaction model. CONCLUSIONS: Our findings suggest that the SULT1A1 His allele was positively associated with the risk of breast cancer in Chinese women. And there was interaction between SULT1A1 polymorphism and related exposure factors.     

GSTP1 A1578G (Ile105Val) polymorphism in benzidine-exposed workers: an association with cytological grading of exfoliated urothelial cells

A polymorphism at codon 105 (Ile/Val) in the GSTP1 gene has been associated with a higher risk for different cancer types. To assess the role of GSTP1 polymorphisms in the development of benzidine-related bladder cancer, GSTP1 AA, AG and GG genotypes were determined in occupationally benzidine-exposed Chinese workers without known disease and benzidine-exposed bladder cancer patients from the same cohort of the Shanghai area. An increased but not significant frequency of GSTP1 AG or GG carriers was observed in the occupationally exposed bladder cancer patient group [odds ratio (OR)=1.95, 95% confidence interval (CI) 0.70-5.46]. The odds ratios for the most important non-genetically determined risk factors for bladder cancer in male individuals were as follows: age (increase per year): OR 1.05, 95% CI 0.99-1.11; ever smoker: OR 1.31, 95% CI 0.47-3.69; duration of exposure (increase per year): OR 1.19, 95% CI 1.10-1.29; and high exposure: OR 4.50, 95% CI 0.70-5.46. Significant differences were found between all benzidine-exposed workers without known disease with modified exfoliated urothelial cells (grade II and higher) and all workers without known disease with at most minor changes (less than grade II) according to Papanicolaou (OR 1.90, 95% CI 1.13-3.20). These findings show for the first time an association between the GSTP1 AG or GG genotype and higher cytological gradings of exfoliated urothelial cells from formerly benzidine-exposed workers.     

Alcohol consumption, glutathione S-transferase M1 and T1 genetic polymorphisms and breast cancer risk

To evaluate the potential association between GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched control subjects with no present or previous history of cancer. A multiplex polymerase chain reaction method was used for the genotyping analyses and statistical evaluations were performed by unconditional logistic regression model. The GSTM1 null genotype was significantly associated with breast cancer risk in premenopausal women [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1-3.7], but not in the postmenopausal women (OR = 0.9, 95% CI = 0.5-1.9), nor in all women grouped together (OR = 1.3, 95% CI = 0.8-1.1). The GSTT1 null genotype posed a similar risk of breast cancer with an OR of 1.6 (95% CI = 1.0-2.5) for the total breast cancer group, OR of 1.7 (95% CI = 0.9-3.2) for pre-menopausal women, and OR of 1.3 (95% CI = 0.6-2.8) for post-menopausal women. The breast cancer risk associated with concurrent lack of both GSTM1 and GSTT1 genes was 2.2 (95% CI = 1.1-4.5), and the risk increased as the number of null genotype increased (P for trend = 0.03). When the data were stratified by the known risk factors of breast cancer, a significant interaction was observed between the GSTM1 genotypes and alcohol consumption (P for interaction = 0.03). An especially remarkable risk of breast cancer was observed for alcohol-consuming premenopausal women lacking both the GSTM1 and GSTT1 genes (OR = 5.3, 95% CI = 1.0-27.8) compared to those with both of the genes. Our findings thus suggest a novel gene-environment interaction which plays an important role in the individual susceptibility to breast cancer. p6     

Chilean pilot study on the risk of lung cancer associated with codon 72 polymorphism in the gene of protein p53

The p53 gene has a polymorphism at codon 72 that presents the arginine or proline genotype, although this polymorphism has been associated with genetically determined susceptibility to lung cancers, the literature has not been consistent with this association. In Chile lung cancer represents the second cause of mortality from cancer. p53 codon 72 polymorphism frequency was studied in a Chilean subpopulation of 133 healthy controls and 111 lung cancer patients. The allelic distribution of the three genotypes (ArgArg, ArgPro, ProPro) in healthy normal controls was 41, 44 and 15%, respectively, which differs slightly from that of lung cancer patients, which was 38, 40 and 22%. A relation between the presence of the Pro allele and lung cancer risk in male smokers was observed. Relative risks were O.R.=2.47 (95% CI: 1.34-4.54) for one single nucleotide polymorphic allele (Pro) and O.R.=3.88 (95% CI: 1.16-13.39) for ProPro genotype.