• Title/Summary/Keyword: null genotype

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Glutathione S-Transferase T1 and M1 Polymorphisms and Risk of Uterine Cervical Lesions in Women from Central Serbia

  • Stosic, Ivana;Grujicic, Darko;Arsenijevic, Slobodan;Brkic, Marija;Milosevic-Djordjevic, Olivera
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3201-3205
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    • 2014
  • The aim of this study was to investigate the frequencies of GSTT1 and GSTM1 deletion polymorphisms in newly-diagnosed patients with uterine cervical lesions from central Serbia. Polymorphisms of GST genes were genotyped in 97 patients with cervical lesions and 50 healthy women using a multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was significantly more prominent among the patients than in controls (74.2% vs 56.0%), the risk associated with lesions being almost 2.3-fold increased (OR=2.26, 95%CI=1.10-4.65, p=0.03) and 3.17-fold higher in patients above >45 years old (95%CI=1.02-9.79, p=0.04). The analysis of the two genotypes demonstrated that GSTM1 null genotype significantly increased risk only for low grade squamous intraepithelial lesion-LSIL (OR=2.81, 95%CI=1.03-7.68, p=0.04). GSTT1 null genotype or different genotype combinations were not found to be risk factors, irrespective to lesion stages, age or smoking. We found that the risk of cervical lesions might be significantly related to the GSTM1 null genotype, especially in women aged above 45 years. Furthermore, the GSTM1 polymorphism might have greater role in development of early stage lesions.

Effect of Glutathione S-Transferase Polymorphisms on the Antioxidant System (Glutathione S-Transferase 유전적 다형성이 항산화 체계에 미치는 영향)

  • Jeon, Gyeong-Im;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.6
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    • pp.708-719
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    • 2007
  • Glutathione S-transferase genotypes GSTT1, GSTM1 and GSTP1 were characterized in 104 healthy male and female subjects and compared with parameters of oxidative stress at the level of DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers and non.smokers. Of the 104 subjects studied, 57.4% were GSTT1 present and 47.6% were GSTM1 present. The GSTP1 polymorphisms a and b were represented as follows: a/a, 75.5%; a/b, 21.6%; b/b type, 2.9%. The GSTT1 null genotype was associated with decreased glutathione in erythrocytes and elevated lymphocytes DNA damage. GST-Px was higher in GSTT1 null compared with GSTT1 present type. The homozygous GSTP1 genotype was not associated with any antioxidant status or DNA damage. The difference in plasma ${\alpha}$-carotene and erythrocytes GSH-Px and GST activities between smokers and non-smokers was detected in the GSTT1 null genotype. Plasma ${\gamma}$-tocopherol and ${\beta}$-carotene decreased significantly in smokers having GSTM1 null genotype. When GSTT1 and GSTM1 were combined, plasma lycopene and erythrocyte GST were reduced in smokers in both null types of these genes. As for GSTP1 genotype, plasma ${\alpha}$-carotene and erythrocytes GSH-Px decreased significantly in smokers with GSTP1 b/b, while erythrocytes GSH-Px activities decreased in smokers with GSTP1 a/b. The different ${\beta}$-carotene level between smokers and non-smokers was seen with both GSTP1 a/a and a/b genotype. It seems that polymorphisms in the phase II metabolizing enzyme glutathione S-transferase may be important determinants of commonly measured biomarkers.

Meta-analysis of the Association Between GSTM1 and GSTT1 Gene Polymorphisms and Cervical Cancer

  • Zhang, Zhen-Yong;Jin, Xue-Ying;Wu, Rong;Wu, Li-Na;Xing, Rui;Yang, Shu-Juan;Xie, Yao
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.815-819
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    • 2012
  • Aim: We conducted a meta-analysis to analyze the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer risk, and explore gene-environment interactions. Methods: Identification of relevant studies was carried out through a search of Medline and the EMbase up to Oct. 2011. All case-control studies that investigated the association between GSTM1 and GSTT1 gene polymorphisms and risk of cervical cancer were included. The pooled odds ratio (OR) was used for analyses of results and the corresponding 95% confidence intervals (CI) were estimated. Results: A total of 21 case-control studies were included in the meta-analysis of GSTM1 (2,378 cases and 2,639 controls) and GSTT1 (1,229 cases and 1,223 controls) genotypes. The overall results showed that the GSTM1 null was related to an increased risk of cervical cancer (OR=1.50, 95% CI=1.21-1.85). Subgroup analysis were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had a moderate increased risk of cervical cancer (OR=1.85, 95% CI=1.07-3.20). For the ethnicity stratification, moderate significantly increased risk of null GSTM1 genotype was found in Chinese (OR=2.12, 95% CI=1.43-3.15) and Indian populations (OR=2.07, 95% CI=1.49-2.88), but no increased risk was noted in others. Conclusion: This meta-analysis provided strong evidence that the GSTM1 genotype is associated with the development of cervical cancer, especially in smokers, and Chinese and Indian populations. However, no association was found for GSTT1 null genotype carriers.

Glutathione-S-Transferase T1 Polymorphism is Associated with Esophageal Cancer Risk in Chinese Han Population

  • Weng, Yuan;Fei, Bojian;He, Ping;Cai, Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4403-4407
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    • 2012
  • Background: Glutathione-S-Transferase T1 (GSTT1) gene has been shown to be involved in the development of esophageal cancer. However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between GSTT1 polymorphism and esophageal cancer risk among Chinese Han population. Methods: Published literature from PubMed, the China National Knowledge Infrastructure and Wanfang Data were searched. Pooled odds ratio (OR) and 95% confidence interval (95%CI) was calculated using a fixed- or random-effects model. Results: Eleven studies with a total of 2779 individuals were included in the meta-analysis. The results showed that GSTT1 null genotype was significantly associated with esophageal cancer risk in Chinese (OR = 1.31, 95%CI 1.12 to 1.53, p = 0.001). Further sensitivity analyses confirmed the significant association. The cumulative meta-analysis showed a trend of an obvious association between GSTT1 null genotype and esophageal cancer risk as information accumulated by year. Conclusions: This meta-analysis suggests a significant association of GSTT1 null genotype with esophageal cancer risk in the Chinese Han population.

The GSTT1 Genotype as A Marker for Susceptibility to Lung Cancer in Korean Female Never-Smokers (한국인 비흡연 여성에서 폐암의 유전적 감수성 표지자로서의 GSTT1 유전자형)

  • Jang, Sang Soo;Jung, Chi Young;Lee, Sin Yeob;Lee, Jae Hee;Jeon, Hyo-Sung;Park, Sun Ha;Son, Ji-Woong;Lee, Eung Bae;Kim, Chang Ho;Kam, Sin;Park, Rang Woon;Kim, In-San;Jung, Tae Hoon;Park, Jae Yong
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.5
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    • pp.485-494
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    • 2003
  • Background : Most previous studies regarding the role of GSTMl and GSTT1 on lung cancer risk have been focused mainly on male smokers. However, epidemiological characteristics, histologic types and risk factors are different in female and male lung cancers, we investigated the association between these genotypes and lung cancer risk in males and females separately. Materials and Methods : The study population consisted of 253 lung cancer (153 males and 100 females) and 243 controls (140 males and 103 females). GSTM1 and GSTT1 genotypes were determined by a multiplex PCR. Results : In the male population, neither GSTM1 nor GSTT1 null genotype showed significant difference between cases and controls. In the female population, the frequencies of GSTM1 null genotype showed no significant difference between cases and controls. However, the frequencies of GSTT1 null genotype was significantly higher in cases (70.3%) than controls (55.3%, odds ratio (OR)=2.18; 95% confidence interval (CI=l.21-3.93). When the female population was stratified by age and smoking status, the ORs for GSTT1 null genotype were significantly higher in subgroups of ${\leq}60$ years (OR=4.82; 95% CI=l.61-14.4) and never-smokers (OR=4.29; 95% CI=1.94-9.48) but not in subgroups of >60 years or smokers. When stratifying the female never-smokers by age, the ORs for GSTT1 null genotype were significantly higher in both age groups of ${\leq}60$ years (OR=7.64; 95% CI=2.00-29.2) and >60 years (OR=2.89; 95% CI=1.05-7.94). Conclusion : We found that GSTT1 null genotype was associated with an increased risk of lung cancer in Korean female never-smokers. This result suggests that GSTT1 null genotype could be used as a biomarker for genetic susceptibility to lung cancer in Korean female never-smokers.

Null Glutathione S-transferase T1 and M1 Genotypes and Oral Cancer Susceptibility in China and India - a Meta-analysis

  • Peng, Jie;Liu, Hong-Zhou;Zhu, You-Jia
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.287-290
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    • 2014
  • Objective: Genetic variation is considered to strongly impact on detoxification of carcinogens and therefore is related to cancer risk. However, findings for the null genotypes of GSTT1 and GSTM1 have not always been consistent. Therefore the present meta-analysis was conducted. Methods: We accessed the reported study at different research areas and used various databases, including PubMed and Wanfang Med Onlion from 1990 to May 1st 2013. We calculated the odds ratio (OR), 95% confidence interval (CI) and P value for oral cancer by using Review Manager 5.1 and STATE 12. Results: We found that there was no increased oral cancer risk among subjects carrying GSTM1 and GSTT1 null genotype (OR=1.35, 95%CI=0.68-2.68, P=0.39) and (OR=1.41, 95%CI=0.72-2.77, P=0.31) in the Chinese population. In contrast, in studies in India a significant correlation between GSTM1 null genotype and oral cancer was observed (OR=1.59, 95%CI=1.20-2.11, P=0.001), but not in GSTT1 (OR=1.21, 95% CI=0.84-1.74, P=0.31). Conclusion: We discovered that GSTM1 deletion polymorphism had a significant effect on the susceptibility of oral cancer in the Indian population.

Impact of Tobacco on Glutathione S Transferase Gene Loci of Indian Ethnics

  • Senthilkumar, K.P.;Thirumurugan, Ramasamy
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5037-5042
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    • 2012
  • Background: Tobacco contains agents which generate various potent DNA adducts that can cause gene mutations. Production of DNA adducts may be neutralized by glutathione S transferase (GST) along with other phase I and phase II enzyme systems. The existence of null type of GST among the population increases the susceptibility to various disorders and diseases. The present study focuses on the impact of high tobacco usage and possible null type mutation in GST loci. Methods: Genotypes of GST were detected by multiplex polymerase chain reaction in unrelated 504 volunteers of high tobacco using natives of Gujarat. Allelic frequencies were calculated using Statistical Package for Social Studies-16 software. Hardy Weinberg Equilibrium (HWE) was calculated using Chi square test. Two sided Fisher's significance test was used to compare allelic frequencies of different populations. Results: The frequency of homozygous null genotype of GSTM1 and GSTT1 were 20% (95% CI 16.7-23.9) and 35.5% (95% CI 31.4-39.9) respectively. The GSTM1 and GSTT1 null allele frequency distribution in the Gujarat population was significantly deviating from HWE. GSTT1 null frequency of Gujaratians was significantly higher and different to all reported low tobacco using Indian ethnics, while GSTM1 was not differing significantly. Conclusion: Tobacco usage significantly influences the rate of mutation and frequency of GSTT1 and M1 null types among the habituates. The rate of mutation in GSTT1 loci was an undeviating response to the dose of tobacco usage among the population. This mutational impact of tobacco on GSTT1 postulates the possible gene - environment interaction and selection of null genotype among the subjects to prone them under susceptible status for various cancers and even worst to cure the population with GSTT1 dependent drugs.

Breeding of Green Soybean Strain with Green Cotyledon and Tetra Null Genotype (Tetra null 유전자형과 녹색종피 및 자엽을 가진 콩 계통 육종)

  • Sarath Ly;Jeong Hwan Lee;Hyeon Su Oh;Se Yeong Kim;Jin Young Moon;Jong Il Chung
    • Journal of Life Science
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    • v.33 no.8
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    • pp.632-638
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    • 2023
  • A soybean cultivar with a green seed coat and cotyledon contains high levels of lutein, which is beneficial for eye health. Plus, antinutritional components such as lipoxygenase, Kunitz trypsin inhibitor (KTI), lectin and stachyose exist in the mature seed. The genetic elimination of these antinutritional factors is a necessary step in green soybean breeding. This research was conducted to improve a new green soybean line with the green cotyledon and tetra null genotype (lox1lox2lox3tilers2) in terms of lipoxygenase, KTI, lectin and stachyose. We used five germplasms to develop a breeding population. A total of 69 F2 seeds were obtained from the cross of parent 1 and parent 2, and from those, 21 F2 seeds were selected that had the green seed coat color, and which were free of lectin protein. Next, four F2 plants with the green seed coat and tetra null genotype were selected from the breeding population derived from four genotypes. The absence of lipoxygenase, KTI and lectin proteins was confirmed in the F5 strain. The breeding line has a green seed coat, green cotyledon and white hilum color. The 100-seed weight and stachyose content for the breeding line were 30.7 g and 2.40 g/kg, respectively. The line selected in this study could be used as a cultivar or parent to improve colored soybean cultivars through the removal of antinutritional components such as lip- oxygenase, KTI, lectin and stachyose.

Glutathione S-transferase M1 Null Genotype and Hepatocellular Carcinoma Susceptibility in China and India: Evidence from an Updated Meta-analysis

  • Liu, Hong-Zhou;Peng, Jie;Peng, Chun-Yan;Yan, Ming;Zheng, Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4851-4856
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    • 2014
  • Background: Glutathione S-transferase M1 (GSTM1) have been reported to be associated with hepatocellular carcinoma. However, the effect of the GSTMl null genotype was divergent in the literature and we therefore performed the present meta-analysis to explore the relationship in detail. Materials and Metbods: Reported studies were searched from 1990 to March 1, 2014 in PubMed and Wanfang Med Online. The total odds oatio (OR) and 95% CI were calculated and analyzed by Review Manager 5.1 and STATE 12. Results: Total OR was calculated from 26 articles with 3,769 cases and 5,517 controls and the association proved significant (OR [95%CI]=1.50 [1.25, 1.80], P<0.05) in the Chinese population. However, there was no significant association between hepatocellular carcinoma risk among subjects carrying the GSTM1 null genotype (OR [95%CI]=1.20 [0.88-1.64], P=0.24) in subgroups of publication in English and in Indian populations (OR [95%CI]=1.80 [0.80-4.20], P=0.15). Conclusions: The GSTM1 deletion polymorphism might not have a significant effect on the susceptibility of hepatocellular carcinoma overall.

Genetic Polymorphisms of Glutathione S-transferase M1 and Prostate Cancer Risk in Asians: A Meta-analysis of 18 Studies

  • Hu, Zheng-Hui;Lin, Yi-Wei;Xu, Xin;Chen, Hong;Mao, Ye-Qing;Wu, Jian;Zhu, Yi;Xu, Xiang-Lai;Xie, Li-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.393-398
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    • 2013
  • Background: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1) null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries is still unclear owing to inconsistencies across results. Methods: We searched the PubMed, Web of Science, Scopus, Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostate cancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: A total of 18 case-control studies with 2,172 cases and 3,258 controls were included in this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased risk of prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001). Similar results were found in East Asians (OR=1.41; 95% CI: 1.12-1.78; P=0.004) and Caucasians in Asia (OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. Conclusions: This meta-analysis of available data suggested that the GSTM1 null genotype does contribute to increased risk of prostate cancer in people who live in Asian countries.