GSTM1 Polymorphisms Research Articles

Analysis of deletion polymorphism of xenobiotics detoxication system genes in patients with tuberculosis and diabetes mellitus

An analysis of the occurrence of alleles and genotypes of GSTM1 gene in patients with pulmonary tuberculosis and diabetes mellitus regarding the MBT resistance version allowed to establish that under the conditions of pulmonary tuberculosis infection GSTM1 gene deletion mutation can be found in one out of five (21.87% of cases), and the occurrence due to the MBT resistance version is: with NDTB - 17.39%, with MDR-TB 35.0% and - PRTB 20.0% respectively. According to the nature of the distribution of allelic gene GSTM1 a favorable functional 1 allele prevails (73.29%) in the normal inbreeding among patients and deficiency of heterozygosity among healthy people, which generally forms a normal population distribution for the European race. Material and methods. The study involved 100 patients with newly diagnosed pulmonary TB and diabetes mellitus who had been hospitalized in Chernivtsi Regional TB Dispensary. The control group consisted of 50 healthy individuals. Genomic DNA was isolated from the whole venous blood. GSTM1 polymorphic areas were isolated by means of multicomplex polymerase chain reaction, according to the protocol for instantaneous analysis of polymorphism by M. Arana et all (1996). Deletion of gene corresponds to the lack of appropriate strips in the electropherogram. Results and discussion. Despite the fact that the activity of the enzyme glutathione-S-transferase of class M is encoded by five GST genes of class M (M1-M5), the dominant cause of genetically caused dysregulation of antioxidant activity is deletion (null) polymorphism of the gene GSTM1. Conclusion. Among the patients with pulmonary tuberculosis and diabetes mellitus one out of five persons (21,87 % of cases) was diagnosed with deletion mutation of GSTM1 gene; and the occurrence due to MBT resistance variation is: in NDTB-17,39 %, in MDR-TB - 35,0 % and in PRTB- 20,0 % respectively.

GSTT1 and GSTM1 polymorphisms with human papillomavirus infection in women from southern Brazil: a case-control study.

BackgroundImportant risk factors for the most common sexually transmitted infection (STI) in the world, human papillomavirus (HPV), include early sexual activity, use of contraceptives, tobacco smoking, and immunological and genetic factors. This study aimed to investigate the relationship between GSTM1 and GSTT1 polymorphisms and HPV infection and associated risk factors in a group of women assisted in the public health system of southwestern Paraná, Brazil.Methods and resultsA case–control study was designed with 21 women with HPV matched by age in the case group and 84 women without the virus in the control group. Viral detection was conducted via polymerase chain reaction (PCR) and GSTM1 and GSTT1 genotyping by Multiplex PCR. The results showed that the GSTT1 null allele was a protective factor against infection (ORadj 0.219; 95% CI 0.078–0.618; p = 0.004). No relationship was observed for the GSTM1 gene. Smoking was defined as a risk factor (ORadj 3.678; 95% CI 1.111–12.171; p = 0.033), increasing the chances of HPV by up to 3.6 times.ConclusionThis study showed, for the first time, the relationship between GSTM1 and GSTT1 genetic polymorphisms and HPV. We found that this relationship protected women from southern Brazil from viral infection, but not from susceptibility.

Genetic Polymorphism of Carcinogen Metabolic Enzymes in Oral Submucous Fibrosis

Background: Biotransformation plays a crucial role in carcinogen activity. Genetic polymorphisms in xenobiotic-metabolizing enzymes crucial to a carcinogen and drug metabolism lead to variations in their activity. These enzymes increase cancer risk by an altered action on environmental carcinogens. The objective of this study was to analyze the significance of genetic polymorphisms in CYP1A1 and GSTM1 (carcinogen-metabolizing enzymes) genes in patients with oral submucous fibrosis (OSMF). Method: The study subjects included 50 patients. Twenty-five were diagnosed with OSMF, 5 with malignant transformation in OSMF, and 20 age and sex-matched healthy controls. Genotypes of CYP1A1 and GSTM1 were determined by polymerase chain reaction-restricted frequency length polymorphism. Results: 10%, 40%, and 60% GSTM1 null genotype were observed in normal subjects, OSMF patients, and OSMF patients with malignancy, respectively. 15%, 48%, and 40% CYP1A1 polymorphism were noted in normal subjects, OSMF patients, and OSMF with malignancy, respectively. Conclusion: Polymorphism in CYP1A1 and GSTM1 null genotype may increase the risk of OSMF. Combined polymorphisms may be an increased risk factor than single-gene polymorphism.

Association between GSTM1, GSTT1 gene polymorphisms and asthma in adult patients from Tikrit population of Iraq

Introduction and Aim: Asthma is known as a polygenic and multifactorial disease. The underlying debate about the role of genetics in the development of asthma is still unclear. The objectives of this research are to examine whether the GSTM1 and GSTT1 gene polymorphisms are associated with asthma susceptibility. Materials and Methods: A total of 70 patients with asthma and 20 healthy individuals were investigated in this study. Genotyping was carried out by using PCR protocol for analysis of GSTM1 and GSTT1 null/positive genotypes. Results: Patients with asthma (34.285%) demonstrated a greater prevalence of the GSTM1, GSTT1 (-) genotype than the healthy subject (10%, P-value 0.012). A positive correlation was found between GSTT1, GSTM1 (+) genotype and healthy individuals (40%) compared with asthmatic patients (24.285%). Conclusion: The results of this research support the idea that GSTM1, GSTT1 (-) genotype may play critical roles in asthmatic inflammatory response. Further experimental investigations are needed to estimate the role of GSTM1 and GSTT1 polymorphisms in asthma.

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism.

PurposeGlutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.Patients and MethodsThis case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.ResultsThe genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42–29.74, P < 0.001).ConclusionIrrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.

Polymorphisms in DNA Repair and Xenobiotic Biotransformation Enzyme Genes and Lung Cancer Risk in Coal Mine Workers.

Background: Currently coal mining employs over 7 million miners globally. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons and radioactive radon, significantly increasing the risk of lung cancer (LC). The susceptibility for LC is modified by genetic variations in xenobiotic detoxification and DNA repair capacity. The aim of this study was to investigate the association between GSTM1 (deletion), APEX1 (rs1130409), XPD (rs13181) and NBS1 (rs1805794) gene polymorphisms and LC risk in patients who worked in coal mines. Methods: The study included 639 residents of the coal region of Western Siberia (Kemerovo region, Russia): 395 underground miners and 244 healthy men who do not work in industrial enterprises. Genotyping was performed using real-time and allele-specific PCR. Results: The results show that polymorphisms of APEX1 (recessive model: ORadj = 1.87; CI 95%: 1.01–3.48) and XPD (log additive model: ORadj = 2.25; CI 95%: 1.59–3.19) genes were associated with increased LC risk. GSTM1 large deletion l was linked with decreased risk of LC formation (ORadj = 0.59, CI 95%: 0.36–0.98). The multifactor dimensionality reduction method for 3-loci model of gene–gene interactions showed that the GSTM1 (large deletion)—APEX1 (rs1130409)—XPD (rs13181) model was related with a risk of LC development. Conclusions: The results of this study highlight an association between gene polymorphism combinations and LC risks in coal mine workers.

Genetic profiles of different ethnicities living in Karachi as regards to tobacco-metabolising enzyme systems and the risk of oral cancer.

To detect polymorphisms of CYP1A1, GSTM1 and GSTT1 gene loci among various tobacco-consuming ethnicities in an urban centre, and to relate these with susceptibility to oral cancer. The cross-sectional, case-control study was conducted at Ziauddin University, Karachi, and the Dow University of Health Sciences, Karachi, from 2011 to 2016, and comprised patients having oral squamous cell carcinoma in group A, with oral precancerous lesions in group B, and tobacco habit-matched controls in group C. Routine histopathology was followed by molecular analysis through polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism techniques. Data was analysed using SPSS 20. Of the 358 subjects, 150(42%) were in group A, 100(28%) in group B, and 108(30%) in group C. There were 190(53.1%) Urdu-speaking subjects, 42(11.7%) Memoni-speaking, 37(10.3%) Sindhi-speaking, 34(9.5%) Balochi-speaking, 25(7%) Pashto-speaking, 15(4.2%) Punjabi-speaking, and 15(4.2) of other ethnicities. Among the Urdu-speaking ethnicity, CYP1A1 MspI heterozygous variant was the most prevalent genotype ingroup A 50(66.7%), group B 37(62.7%) and group C 36(64.3%). The homozygous variant was equally distributed in group A 8(13.5%) and group B 10(13.3%), while it remained quite low in group C 4(7.1%). Homozygous genotype was most common in Pashto-speaking subjects in group A 4(57.1%). In Urdu-speaking subjects, GSTM1-null genotype was mostly found in group B 19(32.2%), while GSTT1-null genotype was most common in group A 12(16%). Other than Urdu-speaking, GSTM1-null variant was most frequent in Sindhi-speaking subjects in group B 8(80%). Intra-ethnic distribution of tobacco-metabolising enzyme genes can be considered an important contributor to oral cancer risk in the population of Karachi.

N-Acetyltransferase 2, Glutathione S-transferase gene polymorphisms and susceptibility to hepatocellular carcinoma in an Algerian population

ABSTRACT This study was conducted to investigate the potential association of genetic polymorphisms of glutathione S-transferase M1/T1 (GSTM1, GSTT1), and N-acetyltransferase 2 (NAT2) genes and epidemiological parameters with the risk of HCC in the Algerian population. A case-control study including 132 confirmed HCC patients and 141 cancer-free controls was performed. Genotyping analysis was performed using conventional multiplex PCR and PCR-RFLP. Statistical analysis was performed using the Chi-square test. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (95% CI). GSTM1 null and NAT2 slow acetylator genotypes confer an increased risk to HCC (OR =1.88, 95% CI 1.16–3.05; OR =2.30, 95% CI 1.26–4.18, respectively). This association was prevalent in smokers (OR =2.00, 95% CI 1.05–3.8 and OR =2.55, 95% CI 1.22–5.34, respectively). No significant association was observed for GSTT1 null genotype in the contribution to HCC risk (OR =0.76, 95% CI 0.46–1.27). In conclusion, the GSTM1 and NAT2 gene polymorphisms are positively associated with the risk of HCC in older men and especially in smokers.

Genetic Polymorphisms and Toxicities of First-Line Antituberculosis Drugs: Systematic Review of the Literature

Introduction: Polymorphisms are the main genetic factors associated with toxicities of antituberculosis drugs. This literature review summarizes the polymorphisms of the genes that code for the enzymes of the metabolism of antituberculosis drugs and their transmembrane transporters. Some mechanisms of drug-associated toxicities and strategies for their management have also been described in this review. Methods: The bibliographic searches were exclusively carried out in PubMed, over a period of ten years (2010-2020). The search terms were the words “toxicity + antituberculosis drug + one or two word(s) among the following: polymorphism, genetics, mutation, SNP, HLA or haplotype”. Publications in English or French, relating to the various toxicities associated with first-line anti-tuberculosis drugs (Rifampicin, Isoniazid, Ethambutol and Pyrazinamide) administered to patients with pulmonary tuberculosis, extrapulmonary tuberculosis or co-infected with TB/HIV were included in this review. Duplicates, in vitro, in silico or drug-induced toxicity studies other than antituberculosis drugs and genetic mutations of Mycobacteria strains were not included. Results: The studies selected and included were case reports, cohort studies, original research, systematic reviews and meta-analyses on human subjects of different ethnic origins. Hepatotoxicity is the most common toxicity associated with NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms in patients on antituberculosis drugs. Other forms of toxicity, less frequent, occurring in certain patients under concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), antiretrovirals (ARVs), antibiotics or antiepileptics have also been identified. Conclusion: The genetic polymorphisms associated with the toxicities of antituberculosis drugs concern both the main enzymes of the metabolic pathways (NAT2, CYP2E1, GST) and the transmembrane transporters (SLCO1B1 and ABCB1). Other genetic polymorphisms (TXNRD1, SOD2, TYMP) have been suspected but their mechanisms are not yet well understood.

Desloratadine Efficacy in Relation to GSTM1 and GSTT1 Polymorphic Genes in Chronic Spontaneous Urticaria.

The etiopathogeny of chronic spontaneous urticaria (CSU) is not well defined. Allelism in glutathione S-transferase GSTM1 and GSTT1 has been suggested as a risk factor. Desloratadine is the first-line treatment for this disease. This study aimed to investigate the efficacy of a first-line treatment: desloratadine 5 mg/day on antioxidant status and clinical assessment in Tunisian patients with CSU and to identify possible associations between GSTT1 and GSTM1 genotypes and susceptibility to CSU. Sixty patients with CSU and 60 age- and gender-matched healthy controls were included in the study. We calculated the urticaria activity score (UAS) and assessed the antioxidant parameters (total antioxidant status [TAS], glutathione S-transferase [GST], SOD, CAT, GPx]). Multiplex PCR was performed to find the relationship between GSTM1 and GSTT1 polymorphisms with CSU susceptibility. At baseline, GST, GPx, CAT, SOD activities, and TAS were significantly lower in CSU patients compared to healthy controls (P < 0.05). After treatment, GST, GPx, CAT, SOD activities and TAS were significantly increased in patients compared to those before treatment (P < 0.001). We observed a significant association in null alleles of GSTM1. Before treatment, GST activity was significantly lower in patients having GSTM1+ genotype than those having GSTM1- genotype (P = 0.001). After treatment, TAS and antioxidant enzymes GST, GPx, SOD, and CAT were significantly elevated in patients having GSTM1- genotype than those having GSTM1+ genotype (P < 0.05). These results suggest the impact of GSTM1 and GSTT1 on CSU susceptibility and desloratadine efficacy in Tunisian patients.

Association of deletion polymorphisms GSTT1 and GSTM1 with increased activity of hepatic transaminases in the blood of patients receiving anti-tuberculosis drug therapy

Association of deletion polymorphisms GSTT1 and GSTM1 with increased activity of hepatic transaminases in the blood of patients receiving anti-tuberculosis drug therapy

Role of Glutathione S-transferase Mu 1 and Glutathione S-transferases Theta 1 Polymorphism in the Risk of Developing Type 2 Diabetes Mellitus at Universitas Sumatera Utara Hospital, Medan

BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. Glutathione S-transferases (GSTs) is group of multifunction antioxidant enzyme can be used as important biomarkers for DM.. GSTM1, T1 genes variant polymorphism result in decreased or loss of enzyme activity.&#x0D; AIM: The study aimed to evaluate the role of GSTM1 and GSTT1 gene polymorphism in the risk of developing T2DM.&#x0D; METHODS: GSTM1 and GSTT1 polymorphisms were genotyped in 87 T2DM patients and 87 healthy control group to analyze their association with T2DM susceptibility by using multiplex Polymerase Chain Reaction (PCR). PCR products were electrophoresed using agarose 2%. Odds ratio (OR) with 95% confidence interval (CI) and P value were calculated using SPSS software (version 21.0).&#x0D; RESULTS: The genotype distribution of GSTM1 and GSTT1 were not different between T2DM patients and healthy control group (p = 0.542, OR= 0.780, CI 95%=0.350-1.737 and p=0.879, OR=1.047, CI 95%=0.577-1.903). The genotype distribution of combination of GSTM1 and GSTT1 were also not not different between T2DM patients and healthy control group (p = 0.640, OR= 0.640, CI 95%=0.224-1.83 and p=0.551, OR=0.721, CI 95%=0.245-2.120.&#x0D; CONCLUSION: In summary, this study showed that GSTT1 null, GSTM1 null, the combination of GSTM1 null and GSTT1 null genotype or combination of GSTM1 null and GSTT1 positive (or contrary) did not have any risk of developing T2DM at Universitas Sumatera Utara Hospital, Medan.&#x0D;

Features of GSTM1, GSTT1 and GSTP1 Genetic Polymorphism in Nizhny Tagil Metallurgical Plant Workers with Cardiovascular Diseases

Background: The development of cardiovascular diseases is determined not only by working conditions but also by genetic characteristics of employees. Genetic GSTM1, GSTT1 and GSTP1 variations contribute to individual differences in responses to industrial chemicals and carcinogens. Objective: To study the features of the genetic polymorphism of the GSTM1, GSTT1, and GSTP1 genes in metallurgical plant workers with diseases of the cardiovascular system in the town of Nizhny Tagil, Sverdlovsk Region, Russian Federation. Materials and methods: The case cohort included 61 men aged 33 to 61 years (mean: 48.15 ± 7.50 years), working in the converter shop and suffering from heart diseases. The control cohort consisted of 29 conditionally healthy male employees, aged 23–56, of the same iron and steel works having no signs of a cardiovascular disease. The DNA was isolated from peripheral blood using a standard technique. Deletion polymorphism of GSTM1 and GSTT1 genes was determined by quantitative PCR; Ile105Val polymorphism of the GSTP1 gene was established by qPCR using a commercial test kit. Results: We observed no statistically significant differences between the cohorts for any of the studied genes. The frequency of occurrence of the combination of GSTM1 (0/0) and GSTT1 (0/0) in the cases and controls was 14 % and 11 %, respectively, but the difference was negligible. Conclusions: Our findings demonstrate that the presence of null genotypes of GSTM1, GSTT1, as well as the mutant GSTP1 allele and the associated loss of enzyme activity contribute little to the development of cardiovascular diseases in workers exposed to occupational hazards.

Influence of GSTM1, GSTT1, and GSTP1 genetic polymorphisms on disorders in transplant patients: a systematic review.

The glutathione-S-transferase (GST) enzymes are phase II isoenzymes responsible for protection against free radicals and xenobiotics. Since these proteins are described as polymorphic, polymorphisms in genes that encode them may alter enzymatic function and contribute to oxidative stress. In this context, such polymorphisms were already associated with several diseases and multiple therapeutic outcomes. A systematic review was performed to evaluate studies regarding the association between polymorphisms in three genes encoding enzymes of the GST family- GSTM1, GSTT1, and GSTP1- and disorders in transplant patients. A total of 125 articles on which inclusion and exclusion criteria were applied were identified at PubMed database. Thirty-two studies met the target criteria and were included in the review. The mechanisms by which GST genotypes influence the development of disorders in transplant patients differ by disorder: they may participate in it by decreasing metabolism of drugs administered to patients undergoing transplantation, then exposing them to greater toxicity; by decreasing the repair ability against oxidative stress; or by encoding proteins that may be recognized as foreign, setting of an alloimmune reaction. Although some results are better established- such as GSTM1 null genotype's role in the development of toxicity events in transplant patients- others require further evidences, as GST influence on the development of pulmonary decline and posttransplant diabetes mellitus (PTDM). The importance of investigating these associations lies in a personalized medicine, in which the high-risk genotype patient has its treatment individualized and its care for prophylaxis and surveillance increased, potentially reducing this population's morbimortality.

Combined GSTT1 Null, GSTM1 Null and XPD Lys/Lys Genetic Polymorphisms and Their Association with Increased Risk of Chronic Myeloid Leukemia.

PurposeGlutathione S-transferases (GSTT1 and GSTM1) are instrumental in detoxification process of activated carcinogens. Nucleotide excision repair is carried out by DNA helicase encoded by xeroderma pigmentosum group D (XPD) genes and aberrations in the XPD gene predisposes to increased risk of cancer. The present study aimed to investigate GSTT1, GSTM1 and XPD polymorphisms in newly diagnosed chronic myeloid leukemia (CML) patients and to examine the association of these polymorphisms with the risk of developing CML.Patients and MethodsThis case–control study was carried out from June 2019 to August 2021 involving 150 newly diagnosed patients with CML and an equal number of randomly selected age- and sex-matched healthy individuals. A multiplex-PCR assay was used to genotype GSTT1 null and GSTM1 null polymorphisms. XPD gene polymorphism was detected by PCR-RFLP using predesigned gene-specific primers.ResultsGSTT1 and GSTM1 null polymorphisms were detected in 42.7% and 61.3% of cases, respectively, compared to 18% and 35.3% for controls. The combination of both GST null polymorphisms revealed a significant association with CML. Frequencies of XPD Lys751Gln genotypes in cases were 62.7% heterozygous Lys/Gln, 24% homozygous Lys/Lys and 13.3% homozygous Gln/Gln, while in the controls were 74.7%, 20%, and 5.3%, respectively. Significant differences were also noted regarding the combination of GSTT1/GSTM1 null with XPD Lys/Lys, and GSTM1 null with XPD Lys/Lys.ConclusionIn conclusion, GSTT1 null, GSTM1 null and XPD polymorphisms showed positive association with the risk of development of CML. Furthermore, age and gender did not exhibit any association with the studied polymorphisms, while CML phases were associated with GSTT1 null polymorphism.

Analysis of the influence of glutathione S-transferase (GSTM1 and GSTT1) genes on the risk of essential hypertension

Background Essential hypertension (EH) results from a complex interaction between environmental factors and an individual’s genetic background. Aim To assess the relationship between polymorphisms in GSTM1 and GSTT1 and the risk of EH. Subjects and methods A multiplex-PCR was used to identify the genotypic profiles of GSTM1 and GSTT1 in 160 patients and 210 controls. Results The frequency of GSTM1-null genotype was higher in patients younger than 61 years when compared to those over 61 years. Interestingly, GSTT1-null was significantly associated with the risk of EH (OR 4; 95% CI 2.6–6.3; p < 0.0001). While GSTM1-null showed no trend (OR 0.7; 95% CI 0.5–1.1, p = 0.12). Individuals carrying the combined GSTT1-null/GSTM1-null were 2.4 times more at risk for hypertension compared to those harbouring the combined GSTT1-present/GSTM1-present genotype (OR 2.4; 95% CI 1.3–4.4; p = 0.005). Additionally, the presence of the combined GSTT1-null/GSTM1-present was associated with an increased risk of EH compared to GSTT1-present/GSTM1-present carriers (OR 6.75; 95% CI 3.4–13.2; p < 0.0001). Conclusion This study showed that the GSTT1-null alone or in interaction with GSTM1-present or GSTM1-null was associated with a higher risk of hypertension. Moreover, the GSTM1-null seems to be associated with the age of onset of hypertension.

Evaluation of molecular markers GSTM1 and GSTT1 and clinical factors in breast cancer: case-control study and literature review

The study was conducted to evaluate the frequency of polymorphisms in GSTM1 and GSTT1 genes in patients with breast cancer compared with individuals without history of cancer, and the association of these polymorphisms with clinical/epidemiological parameters. There were evaluated 752 women (219 patients and 533 controls). Molecular analysis was performed by the Polymerase Chain Reaction (PCR). Statistical analysis was used multiple logistic regression and descriptive statistics. Age ≥ 50 years (OR = 3.22, 95% CI = 2.30–4.51, p < 0.001) and alcohol consumption (OR = 1.60, 95% CI = 1.13–2.27, p = 0.008) were associated to the development of breast cancer, while smoking and null genotypes GSTM1 and GSTT1 presented no association. GSTM1 and GSTT1 polymorphisms presented no relationship with the clinical and histopathological parameters or molecular subtypes of breast cancer. Ninety-two percent of tumours were invasive ductal, 66% were grade II, 65% were larger than 2 cm, the stages II (35.3%) and III (31.2%) were the most prevalent, and 47.7% were molecular subtype luminal B. Individuals aged ≥ 50 years and alcohol consumers have more chance to developing breast cancer. GSTM1 and GSTT1 polymorphisms are not associated to the risk of breast cancer.

Cytokinesis-block micronucleus cytome (CBMN-CYT) assay and its relationship with genetic polymorphisms in welders

Fumes generated in the welding process are composed of micrometric and nanometric particles that form when metal fumes condense. The International Agency for Research on Cancer established that many compounds derived from the welding process are carcinogenic to humans. Still, there are few studies related to the role of genetic polymorphisms. This work aimed to analyze the influence of OGG1 Ser326Cys, XRCC1 Arg280His, XRCC1 Arg194Thr, XRCC1 Arg399Gln, XRCC3 Thr241Met, GSTM1, and GSTT1 gene polymorphisms on DNA damage of 98 subjects occupationally exposed to welding fumes and 100 non exposed individuals. The results showed that individuals exposed to welding fumes with XRCC3 Thr241Thr, XRCC3 Thr241Met, and GSTM1 null genotypes demonstrated a significantly higher micronucleus frequency in lymphocytes. In contrast, individuals with XRCC1 Arg399Gln and XRCC1 Gln399Gln genotypes had significant levels of NPBs. OGG1 326 Ser/Cys, OGG1 326 Cys/Cys, XRCC1 194Arg/Thr, XRCC1 194Thr/Thr, and GSTT1 null genotypes exhibited significantly higher apoptotic values. Also, XRCC1 194Arg/Trp, XRCC1 194Thr/Thr, and GSTM1 null genotype carriers had higher necrotic levels compared to XRCC1 194Arg/Arg and GSTM1 nonnull carriers. Compositional analysis revealed the presence of iron, manganese, silicon as well as particles smaller than 2 μm that adhere to each other and form agglomerates. These results may be associated with a mixture of components, such as nitrogen dioxide, carbon monoxide, and metallic fumes, leading to significant DNA damage and cell death processes. These findings demonstrated the importance of the association between individual susceptibility and DNA damage levels due to occupational exposure to welding fumes; and constitute one of the first studies carried out in exposed workers from Colombia.

The Cumulative Effect of Gene-Gene Interactions Between GSTM1, CHRNA3, CHRNA5 and SOD3 Gene Polymorphisms Combined with Smoking on COPD Risk.

BackgroundChronic obstructive pulmonary disease (COPD) is a multifactorial disorder which is affected by external and internal risk factors. People with no external risk factors may be significantly affected and develop pulmonary disease. The study aimed to define gene–gene and gene–environmental effects on COPD.MethodsA case control study involved 181 COPD patients and 292 healthy individuals, with peripheral blood sampling and adequate questionnaires. Genotyping was done with various types of PCR design for GSTM1 (null del), GSTT1 (null del), EPHX1 (rs2234922 and rs1051740), GSTP1 (rs1695 and rs1138272), CHRNA3 (rs1051730 and rs12914385), CHRNA5 (rs16969968 and rs17486278), and SOD3 (rs1799895 and rs699473) gene polymorphisms. Gene–gene and gene–environmental interactions were investigated using multidimensional regression analysis.ResultsFrequency of risk alleles of rs1051730 (p = 0.001), rs16969968 (p <0.001), and rs1799895 (p <0.001) polymorphisms were significant in univariate analysis. For gene–gene interaction, GSTM1 null, rs1051730, rs16969968, and rs1799895 polymorphisms independently contributed to risk of COPD and any combinations of the risk genotypes have a higher risk of disease. A cumulative effect of the four risk polymorphisms increased the risk of COPD for the smoking index (cOR = 13.6, p <0.001), cigarettes per day (cOR = 32.08, p <0.01), nicotine dependence (cOR = 12.0, p <0.01), and smoking status (cOR = 17.02, p <0.01) for gene–environmental interaction.ConclusionSeveral pivotal genes showed distinct effects for COPD, and some synergistic effects affected the disease progression. The development of COPD was synergistically increased with gene–gene and gene–environmental risk factors.

Role of Glutathione S-Transferase M1 and Glutathione S Transferase Theta 1 Gene Polymorphism, Histopathological, and Immunohistochemistry in Carcinoma Breast

Background:Breast cancer is the most common invasive cancer in females in developing countries such as India. It is the most common malignancy in females in the Punjab state.Objectives:(1) The purpose of this study was to calculate the prevalence of the four subtypes of breast cancer based on molecular classification and (2) to determine the association of polymorphisms in Glutathione S-Transferase M1 (GSTM1) and Glutathione S transferase theta 1 (GSTT1) gene in carcinoma of the breast with histopathological grading.Materials and Methods:This study analyzed histologically confirmed 100 cases of carcinoma breast; immunohistochemistry and reverse transcription polymerase chain reaction molecular tests were performed for further grading, molecular typing, and gene polymorphism.Results:Out of 24 Grade I tumors, 18 (75.00%) expressed the GSTM1 gene and 6 (25.00%) were negative. Out of 48 Grade II tumors, 30 (62.50%) expressed the GSTM1 gene and 18 (37.50%) were negative. Out of 28 Grade III tumors, 8 (28.57%) expressed the GSTM1 gene and 20 (71.43%) were negative. Out of 24 Grade I tumors, 17 (70.83%) expressed the GSTT1 gene and 7 (29.17%) were negative. Out of 48 Grade 2 tumors, 28 (58.33%) expressed the GSTT1 gene and 20 (41.67%) were negative. Out of 28 Grade III tumors, 8 (28.57%) expressed the GSTT1 gene and 20 (71.43%) were negative.Conclusion:Our study shows that polymorphism of both GSTM1 and GSTT1, either individually or in combination, influences the risk of developing carcinoma due to DNA damage caused by many factors including environmental and genetic.