• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7165-7169
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• 2013

Purpose: The aim of this study was to evaluate any association of GSTM1 and GSTT1 null genotypes with the risk of lung cancer in a South Korean population. Methods: We conducted a large-scale, population-based case-control study including 3,933 lung cancer cases and 1,699 controls. Genotypes of GSTM1 and GSTT1 were determined using real-time polymerase chain reaction. Results: In logistic regression analysis adjusted for age and smoking, we did not find any association between GSTM1 or GSTT1 and LC risk in women. However, in men, the GSTM1 and GSTTI null genotypes were borderline associated with risk (OR=1.18, 95% CI=0.99-1.41 for GSTM1, OR=1.18, 95% CI=0.99-1.41 for GSTT1), and combined GSTM1 and GSTT1 null genotypes conferred an increased risk for LC in men (OR=1.39, 95% CI=1.08-1.78). The OR for the GSTT1 null genotype was greater in subjects aged 55 years old or younger (OR=1.45, 95% CI=1.09-1.92 for men; OR=1.36, 95% CI=0.97-1.90 for women), than in those over age 55 (OR=1.03, 95% CI=0.83-1.27 for men; OR=0.86, 95% CI=0.66-1.12 for women) in both genders (p for interaction <0.05). Conclusions: In the Korean population, the GSTM1 and GSTT1 null genotypes are risk factors for LC in men; the GSTT1 null genotype has a more prominent effect on LC risk in younger people (age 55 years and under) than in older individuals.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5019-5022
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• 2012

Objective: To evaluate the predictive value of GST gene polymorphisms with regard to prognosis of breast cancer patients receiving neoadjuvant chemotherapy. Methods: A total of 159 patients were included in our study between January 2005 and January 2007. All the patients were followed up until January 2012. Genotyping was based upon the duplex polymerase-chain-reaction with the PCR-CTPP method. Results: Patients with null GSTM1 and GSTP1 Val/Val genotypes had significantly had better response rates to chemotherapy when compared with non-null GSTM1 and GSTP1 Ile/Ile genotypes (OR=1.96 and OR=2.14, respectively). Patients with the GSTM1 null genotype had a longer average survival time and significantly lower risk of death than did those with non-null genotypes (HR=0.66). Similarly, those carrying the GSTP1 Val/Val genotype had 0.54-fold the risk of death of those with GSTP1 Ile/Ile (HR=0.54). Conclusion: A significant association was found between GSTM1 and GSTP1 gene polymorphisms and clinical outcomes in breast cancer cases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4725-4732
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• 2012

Aim: The incidence of stomach cancer in Mizoram is highest in India. We have conducted a population based matched case-control study to identify environmental and genetic risk factors in this geographical area. Methods: A total of 102 histologically confirmed stomach cancer cases and 204 matched healthy population controls were recruited. GSTM1 and GSTT1 genotypes were determined by PCR and H. pylori infections were determined by ELISA. Results: Tobacco-smoking was found to be an important risk factor for high incidence of stomach cancer in Mizoram. Meiziol (local cigarette) smoking was a more important risk factor than other tobacco related habits. Cigarette, tuibur (tobacco smoke infused water) and betel nut consumption synergistically increased the risk of stomach cancer. Polymorphisms of GSTM1 and GSTT1 genes were not found to be directly associated with stomach cancer in Mizoram. However, they appeared to be effect modifiers. Persons habituated with tobacco smoking and/or tuibur habit had increased risk of stomach cancer if they carried the GSTM1 null genotype and GSTT1 non-null genotype. Conclusion: Tobacco smoking, especially meiziol is the important risk factor for stomach cancer in Mizoram. GSTM1 and GSTT1 genes modify the effect of tobacco habits. This study is a first step in understanding the epidemiology of stomach cancer in Mizoram, India.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6263-6267
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• 2012

Background: Glutathione-S-transferase (GST) is an important phase II xenobiotic compound metabolizing enzyme family, involved in tolerance to a particular drug or susceptibility to a diseasec. This study focused the GSTM1 and T1 null allele frequency in the Gujarat population with a comparison across other Inter- and Intra-Indian ethnic groups to predict variation in the possible susceptible status. Methods: DNA was isolated by a salting out method and GSTM1 and T1 homozygous null genotypes were detected by multiplex polymerase chain reaction in 504 unrelated individuals. The genotype distribution of null alleles was compared with Indian and non Indian ethnics reported earlier in the literature using Fisher's test. Results: The frequencies of the homozygous null genotypes of GSTM1 and GSTT1 were 20% (95%CI 16.7-23.9) and 35.5% (95%CI 31.4-39.9) respectively. GSTM1 null frequency did not deviate from most other Indian ethnic groups but differed from the majority of those of non Indian ethnicity studied. The frequency of homozygous null type of GSTT1 was significantly higher and deviated from all Indian groups and a few of non Indian ethnicity. Conclusions: Gujarat ethnicity, possibly the most susceptible for GSTT1 dependent drug disposition and diseases regarding effects of pollution. Further, the results have implications for GSTT1 dependent drugs used for treatment, a serious problem which needs to be solved by physicians and clinical researchers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2075-2081
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• 2014

The association between glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1) and risk of acute leukemia in Asians remains controversial. This study was therefore designed to evaluate the precise association in 23 studies identified by a search of PubMed and several other databases, up to December 2013. Using random or fixed effects models odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Heterogeneity across studies was assessed, and funnel plots were constructed to test for publication bias. The meta-analysis showed positive associations between GST polymorphisms (GSTM1 and GSTT1 but not GSTP1) and acute leukemia risk [(OR=1.47, 95% CI 1.18-1.83); (OR=1.32, 95% CI 1.07-1.62); (OR=1.01, 95% CI 0.84-1.23), respectively] and heterogeneity between the studies. The results suggested that the GSTM1 null genotype and GSTT1null genotype, but not the GSTP1 polymorphism, might be a potential risk factors for acute leukemia. Further well-designed studies are needed to confirm our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.781-784
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• 2016

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6429-6438
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• 2015

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ${\leq}35$ or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1515-1518
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• 2012

Aim: We conducted a prospective study in an Chinese population to detect the association between GSTM, GSTT and GSTP gene polymorphisms and survival of gastric cancer. Methods: A prospective follow-up study with 317 gastric cancer patients was conducted between January 2003 and January 2005. GSTM1, GSTT1 and GSTP1 genotyping was performed using ABI TaqMan Gene Expression assays. Results: Of 317 patients, 5 were lost to follow-up due to migration, while the remaining 302 patients completed the study. The median follow-up time was 34.2 months (range: 2 to 60 months), during which a total of 120 (39.1%) died of gastric cancer. The GSTT1-null genotype showed a significant increased risk of death from gastric cancer, with an HR (95% CI) of 1.59 (1.04-3.58). Moreover, we found individuals carrying null-GSTM1 and null-GSTT1 had a moderate higher risk of death from gastric cancer, with an HR of 1.92 (1.05-3.65). Conclusion: This study reported the carriage of null GSTT1 and null GSTM1 might be linked to the higher death risk from gastric cancer in Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3345-3349
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• 2013

Background: Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation in lung cancer incidence with ethnicity. Materials and Methods: We conducted a case-control study of 218 northern Indian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lung cancer in our population. Results: We observed a significant difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=1.87, 95%CI: 1.25-2.80-0.73, P=0.002). However, GSTM1 null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Conclusions: Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.