GSTM1 Null Polymorphism Research Articles

Glutathione S-transferase polymorphisms in varicocele patients: a meta-analysis

The glutathione S-transferase (GST) family represents a major group of detoxification and antioxidant enzymes. Studies have shown that high oxidative stress levels are associated with varicocele. The objective of this study was to assess the relationship between GSTM1 and GSTT1 null polymorphisms and varicocele using a study group of 497 varicocele patients and 476 control subjects. A systematic literature search (for articles published up to September 2014) utilizing Google Scholar and PubMed was conducted. The chi-square-based Q test and I(2) index were used to evaluate data from retrieved studies. The possible publication bias was evaluated by Begg funnel plot and the Egger test. No statistically significant association was found between GSTM1 or GSTT1 null genotypes and varicocele in the overall data analysis. In a subgroup analysis, only the null GSTM1 genotype was observed at a significantly higher frequency in Caucasian varicocele patients. In the Chinese subgroup, no association was established between the GSTM1 and GSTT1 null genotypes and this condition. More attention should be drawn to oxidative stress-related pathological manifestations for Caucasian varicocele patients.

Association of the GSTM1 null polymorphism with breast cancer in a Mexican population.

The glutathione S transferase (GST) family plays an important role in the processing of carcinogens. Data on the null GSTM1 genotype has revealed associations with cancer, and has been suggested to affect carcinogen metabolism and to contribute to tumor promotion in the mammary gland. We examined the role of the null GSTM1 genotype by comparing the genotypes of 276 healthy Mexican women with those of 558 Mexican women with breast cancer (BC). The genotype frequencies observed in the controls and patients with BC were 38 and 45% for the null GSTM1 genotype, respectively. The obtained odds ratio (OR) was 1.36, with a 95% confidence interval (95%CI) of 1.02-1.8, P = 0.04. The protective association was also evident upon analysis of the distributions of the null GSTM1 genotype in patients with positive chemotherapy response who had high plasma levels of glucose (OR 0.56, 95%CI = 0.33-0.94, P = 0.03). This study suggested that the null GSTM1 genotype is associated with BC susceptibility in the Mexican population analyzed.

Polymorphisms of GSTM1, GSTT1, and p53 in Goiânia, Goiás.

Genetic polymorphisms are defined as changes within the DNA sequences of genes that have frequencies in the population higher than 1%. The glutathione S-transferases play an important role in the cellular detoxification systems involved in oxidative stress that can lead to accumulation of reactive oxygen species. Epidemiological studies have suggested that individuals with homozygous deletion of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) are at higher risk of developing several types of neoplasias. The p53 protein is highly expressed in tumors and transformed cells, and the p53 is a classical tumor suppressor gene involved in regulating cell growth and development. In this study, we investigated the prevalence of polymorphisms in the p53, GSTM1, and GSTT1 genes in a population from Goiânia. We evaluated the polymorphisms of these genes in peripheral blood samples. The null or present polymorphism of GSTM1 and GSTT1 genes and Arg/Pro of the p53 gene were analyzed. Our results revealed a higher frequency of the GSTM1-null polymorphism (72.4%) than the GSTM1-present genotype (27.6%). For GSTT1, we observed higher frequency for the null genotype (65.5%) compared to the present genotype (34.5%). Analysis of p53 gene polymorphisms showed a higher frequency for the genotype Arg/Pro (66%) and a lower frequency for the Arg/Arg (23%) and Pro/Pro (11%) genotypes. It is essential to understand polymorphism frequencies in different populations and to evaluate the role of genetic polymorphisms and their effects on health.

Analysis of the GSTM1-null polymorphism in patients with pterygium from Goiânia, Goiás Brazil.

The first reports about pterygium date back to Hippocrates, and this disease still threatens vision health around the world. Pterygium is a formation of fibrous tissue consisting of highly vascularized epithelial and subepithelial tissue that grows excessively and with an abnormal shape on the cornea. Many physical and biological factors are associated with the pathogenesis of pterygium, including heat, dust, and other particles in the atmosphere, and immunological mechanisms, mechanisms involving extracellular matrix reorganization, growth factors, cytokines, apoptosis, and angiogenesis. The aim of this study was to further investigate the association between polymorphisms in GSTM1 and the formation of pterygium. We collected peripheral blood samples from 90 patients diagnosed with pterygium and from 23 subjects with-out the disease in order to perform molecular analysis of the GSTM1 gene. Subjects with one or two copies of the GSTM1 allele had a normal genotype while those without any copies of the allele had a null geno-type. The chi-square test or the Fisher exact test was performed in order to investigate possible associations between the molecular analysis and the risk of pterygium. A significant difference between the frequency of the GSTM1-null genotype in patient and control groups was identified. However, sub-group analysis found that the GSTM1-null genotype was statistically significant in men, but not in women, and in Caucasians, but not in Brown or Black groups. Furthermore, the GSTM1-null geno-type was not related to any of the risk factors analyzed: cases in family, occupational exposure, smoking, hypertension, and diabetes.

Abstract B20: Polymorphism analyses in specific xenobiotic-metabolizing genes of Hispanic farmworkers from the San Joaquin Valley with hormone-dependent cancer

Abstract Organochlorines (OC) are a common class of pesticides known as endocrine disruptors in humans. OC pesticides are known to modify the effects of estrogen and testosterone and may act as agonists or antagonists or have mixed effects in the microenvironment of tissues. The pathway to pesticide (xenobiotic) elimination from the body is a multi-step process resulting in excretion of contaminants through the urine or bile. The first step involves oxidation which is primarily carried out by the Phase I enzyme family, cytochrome P450 (CYP), and is typically an activating reaction creating a more polar byproduct. The second step involves conjugation with an endogenous ligand through a Phase II enzyme family, glutathione-S-transferase (GST), and is typically a detoxifying reaction. The goals of this study have been to determine the association between exposure to OC pesticides and risk of a hormone-dependent cancer (breast or prostate) in the Hispanic population of the intensely agricultural San Joaquin Valley of California. Our case-control study involves the use of DNA samples consented from 42 Hispanic female participants and 180 Hispanic male participants and assesses single nucleotide polymorphisms (SNPs) in select xenobiotic-metabolizing genes utilizing three different molecular strategies. For female samples, we found no association between the GSTM1 null polymorphism and breast cancer risk in this sample (O.R. = 0.99, 95% CI=0.28, 3.51), but did find a doubling in breast cancer risk among those women who carried the null polymorphism for GSTT1 (O.R. = 2.21, 95% CI=0.39, 12.63). In females, two CYP1B1 polymorphisms (codon 119 Ala/Ser and codon 432 Val/Leu) were also genotyped. While no association in breast cancer risk for codon 119 (O.R. = 0.77, 95% CI=0.14, 3.70) was found, we did find elevated risk of breast cancer (O.R. 2.33, 95% CI= 0.64, 8.54) at codon 432 (Val>Leu) suggesting that women carrying the Val CYP1B1 allele had higher risk than those women with the Leu/Leu genotype. Due to the small sample population, Odds Ratios are deemed statistically unstable and thus one must be prudent in drawing firm conclusions. Analyses of male samples are ongoing. This study indicates that it is feasible to identify, trace, consent and recruit female and male Hispanic participants in the San Joaquin Valley of California who have recently been diagnosed with breast cancer or prostate cancer for future interventional studies. Citation Format: Yesenia Ibarra, Malika Sahni, Kathryn Patterson, Jessica Borba, Jason A. Bush, Paul K. Mills. Polymorphism analyses in specific xenobiotic-metabolizing genes of Hispanic farmworkers from the San Joaquin Valley with hormone-dependent cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B20. doi:10.1158/1538-7755.DISP13-B20

GSTM1 polymorphism and lung cancer risk among East Asian populations: a meta-analysis

GSTM1 gene encodes a key enzyme involved in the metabolism of xenobiotics, and its polymorphisms have been related to individual susceptibility to several malignancies. Many molecular epidemiological studies were performed to investigate the association between the GSTM1 null polymorphism and lung cancer susceptibility in East Asia. However, the results were inconsistent. In order to derive a more precise estimation, we conducted this meta-analysis involving 5,909 lung cancer cases and 7,067 controls from 35 studies. We used crude odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the association between GSTM1 null genotype and the risk of lung cancer. Our study found that the GSTM1 null genotype appeared to be a significant risk factor for lung cancer in East Asia population (OR = 1.30, 95 % CI = 1.17-1.45, P heterogeneity < 0.0001, and I (2) = 54.0 %).

GSTM1 null polymorphism – a possible key for oral carcinogenesis

Carcinogenesis is a multistep process and individual risk to development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on genetic susceptibility of an individual. In head and neck cancer, tobacco exposure and alcohol consumption are predominantly the most significant external factors for tumor formation. Individual’s susceptibility to cancer may be partly explained by variability in enzymatic activities of metabolic genes. Mutations in genes concerned with production of enzymes for metabolism of tobacco products may lead to increased risk of carcinogenesis with respect to oral mucosa. Therefore variations in the expression of these genes due to heritable genetic polymorphisms might modulate the process of carcinogenesis by altering the exposure levels of tobacco derived carcinogens. Objective: This non systematic review summarizes current data available on the role of environment gene interaction in form of GSTM1 null polymorphism and oral carcinogenesis. Literature review: Relevant data was selected in order to summarize the studies conducted on GSTM1 null polymorphism and oral cancer. Conclusion: Relationship between GSTM1 null polymorphism in oral cancer needs to be established to confirm the role of environment gene interaction in oral carcinogenesis.

Glutathione S-Transferase T1 and M1 Polymorphisms Are Associated with Lung Cancer Risk in a Gender-Specific Manner

Background: Glutathione S-transferase (GST) T1 and M1 are detoxification enzymes which neutralize various carcinogenic compounds. Polymorphisms of the GSTT1 and GSTM1 genes which encode the enzymes could be associated with cancer risk. Patients and Methods: We investigated the association of GSTT1 and GSTM1 null polymorphisms with lung cancer risk in a tightly matched, considerably large sample in China. Genotyping was performed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing, and associations were measured by using logistic regression analysis. Results: We found that the null genotypes of both polymorphisms resulted in an increased lung cancer risk, with an odds ratio (OR) of 1.57 (95% confidence interval (CI) 1.23-2.00) for GSTT1 and OR 1.87 (95% CI 1.46-2.39) for GSTM1 (p < 0.01). Significant associations remained after stratification by histopathology (p < 0.01) and smoking status (p < 0.05). When gender-stratified association was performed, we found that the GSTT1 null genotype resulted in an increased risk among males (adjusted OR 2.95, 95% CI 2.07-4.20; p < 0.01) but not females (p > 0.05), while the GSTM1 null genotype resulted in an increased risk among females (adjusted OR 2.18, 95% CI 1.54-3.10; p < 0.01) but not males (p < 0.05). Conclusion: Polymorphisms in GSTT1 and GSTM1 are associated with the risk of lung cancer in a gender-specific manner.

GSTM1 null polymorphisms is associated with laryngeal cancer risk: a meta-analysis

Many studies have examined the association between the GSTM1 (null or non-null genotype) polymorphism and laryngeal cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. PubMed was searched for case-control studies published up to December 2013. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 23 studies, comprising 2,562 laryngeal cancer cases and 4,091 controls, were included. Overall, for null versus present, the pooled OR was 1.22 (95 % CI = 1.10-1.36), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR = 1.71; 95 % CI = 1.34-2.19; P = 0.011 for heterogeneity) and in Caucasians (OR = 1.13, 95 % CI = 1.00-1.27; P = 0.036 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism is an increased risk of laryngeal cancer in Asians and Caucasians.

Effect of polymorphic metabolizing genes on micronucleus frequencies among benzene-exposed shoe workers in China

It is well-known that metabolism of benzene is required for the induction of toxicity and consequent health problems. Therefore, genetic variation in benzene (BZ) metabolism genes can influence health outcomes. However, large population studies are needed to provide more evidence for such relationship. We have conducted a large population investigation (385 BZ-exposed shoe workers and 197 matched healthy controls) on the association between inheritance of certain BZ metabolizing genes and the expression of micronuclei (MN). The latter was based on the cytokinesis-blocked MN assay. We analyzed the polymorphisms of GSTM1, GSTT1, GSTP1 (rs1695), CYP2E1 (rs3813867), CYP2E1 (rs2031920), CYP2E1 (rs6413432), mEH exon 3 (rs1051740), mEH exon 4 (rs2234922). Univariate Poisson regression analysis demonstrated that the BZ-exposed workers had significantly increased MN frequency compared with the controls (FR=1.84, 95% CI: 1.56-2.18; P<0.001), and showed a cumulative exposure dose-response relationship. The CYP2E1 rs3813867 mutant allele (CC+GC) (FR 1.15, 95% CI 1.02-1.29; P=0.020) and rs2031920 variant allele (CT+TT) (FR=1.23, 95% CI: 1.09-1.37, P<0.01) was associated with higher MN frequency significantly compared with the wild genotype separately. Furthermore, the MN frequency in rs2031920 variant allele (CT+TT) (FR=1.17, 95% CI: 1.04-1.31, P<0.01) was also higher than the wild genotype when the age, gender and cumulative exposure dose was adjusted in Poisson regression. In addition, the CYP2E1, however, GSTM1null, GSTT1null, GSTP1 rs1695, rs6413432, rs1051740 and rs2234922 polymorphisms showed no association with MN frequency. Our results indicate that two promoter polymorphisms in the CYP2E1 gene, especially the rs2031920 variant allele, were involved with the BZ-induction of MN and may contribute to risk of cancer among exposed workers.

Polymorphisms in the GSTT1 and GSTM1 genes are associated with increased risk of preeclampsia in the Mexican mestizo population

Preeclampsia is a pregnancy-specific disorder in humans and a major cause of maternal and neonatal morbidity and mortality. Increasing evidence suggests that oxidative stress plays an important role in the pathogenesis of preeclampsia. The aim of this study was to investigate the relationship between null alleles of the glutathione S-transferases (GST) M1 and T1 genes and the risk of preeclampsia. This case-control study involved 112 preeclamptic and 233 normoevolutive pregnant women. The null polymorphisms were genotyped by multiplex polymerase chain reaction (PCR). Our results showed an increased risk of preeclampsia in patients with the GSTT1 null genotype [odds ratio (OR) = 2.21; 95% confidence interval (CI) = 1.14-4.27; P = 0.018]. Our data further showed that a combination of deletion genotypes of the GSTM1 and GSTT1 genes conferred an even higher risk of preeclampsia (OR = 4.56, 95%CI = 1.59-13.09; P = 0.005). Our results provide the first evidence suggesting that a GSTT1 null polymorphism might be associated with preeclampsia in the Mexican mestizo population, and that this risk increases with the combination of both GSTT1 and GSTM1 null polymorphisms.

Association of glutathione S-transferase M1, T1, and P1 polymorphisms with renal cell carcinoma: evidence from 11 studies

The glutathione S-transferases (GSTs) are a gene superfamily of phase II metabolic enzymes that has attracted a considerable attention as a candidate gene for renal cell carcinoma (RCC) based on its enzyme function as a key factor in biotransformation pathways. In the past decade, a number of case-control studies were conducted to investigate the association of GST genetic polymorphisms and RCC risk. However, studies on the association between GST (GSTM1, GSTT1, and GSTP1) polymorphisms and RCC remain to be conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 2,189 cases and 3,817 controls from 11 case-control studies was performed. Overall, the summarized odds ratio for RCC of the GSTM1 null and GSTT1 null polymorphisms was 1.02 (95% confidence interval (CI) 0.91-1.15, P = 0.70) and 1.28 (95% CI 0.96-1.72, P = 0.09), respectively. No significant results were observed in heterozygous and homozygous genotypes when compared with wild-type genotype for GSTP1 I105V polymorphism. However, the GSTM1-GSTT1 interaction analysis showed that the dual null genotype of GSTM1/GSTT1 was significantly associated with an increased RCC risk (odds ratio (OR) = 1.42, 95% CI 1.14-1.76, P = 0.001). In the stratified analyses by ethnicity, significant gene-disease association was obtained among Asians for GSTT1 and GSTP1 polymorphisms. In our meta-analysis, the associations between variations of GSTs and RCC may vary in different ethnic populations, and the interaction between unfavorable GST genotypes may exist.

Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo

BackgroundSome studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo. AimsThe purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo. MethodsWe carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0. ResultsSix case–control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR=1.59, 95% CI: 1.21–2.08, P=0.001; GSTT1: OR=1.30, 95% CI: 1.12–1.51, P=0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR=1.71, 95% CI: 1.12–2.63, P=0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR=1.76, 95% CI: 1.15–2.71, P=0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans. ConclusionThe GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion.

Correction: Corrigendum: GSTM1 and GSTT1 null polymorphisms and male infertility risk: an updated meta-analysis encompassing 6934 subjects

Published data on the association between the GST genes polymorphisms and male infertility risk are inconclusive. We investigated GST genes polymorphisms in a large sample size case-control study, and conducted a literature-based meta-analysis of 6934 individuals. Our case-control study showed the GSTM1 null genotype was significantly associated with idiopathic oligozoospermia, while the null genotype of GSTT1 was significantly associated with normozoospermia and azoospermia. Additionally, significantly elevated GSTT1 expression levels were observed in present genotype compared with null genotype. In the meta-analysis, the null genotype of GSTM1 was associated with a significantly increased risk of male infertility. Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism was associated with male infertility in both Asian and Caucasian groups. Further studies of GSTM1 and GSTT1 with their biological functions are needed to understand the role of these genes in the development of male infertility.

Impact of glutathione-S-transferases (GST) polymorphisms and hypermethylation of relevant genes on risk of prostate cancer biochemical recurrence: a meta-analysis.

IntroductionAccurate prediction of the biochemical recurrence (BCR) is critical for patients after intended curative therapy like radical prostatectomy (RP) or definitive radiotherapy for prostate cancer. Glutathione-S-transferases polymorphisms as well as hypermethylation of GSTP1 and functional genes in carcinogenesis, including tumor suppression gene (APC), hormone receptor that regulates cell growth and differentiation gene (RARbeta) were reported to be associated with BCR. Nevertheless, the reported results are inconsistent. To evaluate the relationship between glutathione-S-transferases polymorphisms and hypermethylation of these genes and the risk of prostate cancer BCR, we carried out a meta-analysis of the published studies.Methods and MaterialsWe performed a search in Medline, Embase and CNKI database with GST, APC, RARbeta in combination with single nucleotide polymorphism, hypermethylation, prostate cancer and recurrence. Languages were restricted to English and Chinese.ResultsOur study included 4 case-control studies and 7 cohort studies including 12 data sets and 3,037 prostate cancer patients. We confirmed that APC hypermethylation is associated with a modest hazard for biochemical recurrence after RP (HR = 1.85, 95%CI = 1.12–3.06). We also suggest GSTP1 polymorphism and CpG hypermethylation tested in serum are associated with BCR (HR = 1.94, 95%CI = 1.13–3.34). We also identified a possible association between GSTM1 null polymorphism and prostate cancer biochemical recurrence risk with borderline significance (HR = 1.29, 95%CI = 0.97–1.71).ConclusionTo our knowledge, this is the first meta-analysis evaluating the relationship of polymorphisms and hypermethylation in GSTs and biochemical recurrence. GSTM1, GSTP1 polymorphisms and hypermethylation of GSTP1, APC may be potential biomarkers for the evaluation of the probability of BCR. Further studies are warranted to validate these findings in larger cohorts with longer follow-up.

GSTM1 null polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the GSTM1 null gene polymorphism and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and Embase databases were searched for case-control studies published up to May 2013. Data were extracted and pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 39 studies, comprising of 4,704 oral cancer cases and 7,090 controls, were included. Overall, for null versus present, the pooled OR was 1.29 (95% CI = 1.20-1.40), and the heterogeneity was found in all studies. In the stratified analysis by ethnicity, significant risks were found among Asians (OR = 1.39, 95% CI = 1.27-1.53; P = 0.000 for heterogeneity), but not in Caucasians (OR = 0.99, 95% CI = 0.83-1.18; P = 0.677 for heterogeneity). In conclusion, this meta-analysis demonstrates that the GSTM1 null gene polymorphism may be an increased risk of oral cancer in Asians but not in Caucasians.

GSTM1 and GSTT1 null polymorphisms and male infertility risk: an updated meta-analysis encompassing 6934 subjects

Published data on the association between the GST genes polymorphisms and male infertility risk are inconclusive. We investigated GST genes polymorphisms in a large sample size case-control study, and conducted a literature-based meta-analysis of 6934 individuals. Our case-control study showed the GSTM1 null genotype was significantly associated with idiopathic oligozoospermia, while the null genotype of GSTT1 was significantly associated with normozoospermia and azoospermia. Additionally, significantly elevated GSTT1 expression levels were observed in present genotype compared with null genotype. In the meta-analysis, the null genotype of GSTM1 was associated with a significantly increased risk of male infertility. Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism was associated with male infertility in both Asian and Caucasian groups. Further studies of GSTM1 and GSTT1 with their biological functions are needed to understand the role of these genes in the development of male infertility.

The protective effect of coffee consumption on cutaneous melanoma risk and the role of GSTM1 and GSTT1 polymorphisms

The authors examined the association between coffee consumption and cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms. A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 controls. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected for all subjects. Within the study, individual patterns at two polymorphic genes (GSTM1 and GSTT1) belonging to glutathione S-transferases family were investigated in 188 cases of cutaneous melanoma and 152 controls. Logistic regression was the method used to estimate odds ratio and 95 % confidence intervals. High frequency of coffee drinking (>once daily), compared with low-frequency consumption of coffee (≤7 times weekly) was associated with a protective effect for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age, education, hair colour, common nevi, skin phototype, and sunburn episodes in childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of coffee was extremely high for subjects with both GSTM1 and GSTT1 null polymorphisms (OR 0.01; 95 % CI 0.0003-0.54). Our results show a protective effect of coffee consumption for cutaneous melanoma, in particular for those with homozygous deletion for GSTM1 and GSTT1.

Associations of CYP1A1, GSTM1 and GSTT1 Polymorphisms with Lung Cancer Susceptibility in a Northern Indian Population

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. 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. 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). 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.

English

The Mother and Child Environmental Cohort (MACE) study piloted in South Africa in 2010 to 2011, collected genetic, biochemical and clinical data from pregnant females residing in south and north Durban. We evaluated birth outcomes and the influence of GSTM1pos→GSTM1null and theGSTP1 (Ile105Val; AA→AG/GG) polymorphisms on the extent of DNA damage and with biomarkers [glutathione (GSH) and malondialdehyde (MDA)] related to oxidative stress in mothers with different levels of pollutant exposure. There was no significant difference in adverse birth outcomes or genotype distribution between mothers from the exposed and lower exposed areas. Mean GSH and comet tail length did not differ significantly between GSTM1pos and GSTM1null genotypes. When stratified by genotype, mean MDA levels was higher among GSTM1 null mothers compared to the GSTM1pos mothers (p = 0.01). When each of the genotypes was stratified by exposure, mean GSH concentration was significantly higher in north Durban for theGSTM1pos, GSTM1null and GSTP1AG+GG genotypes (p < 0.05), and mean comet tail length was significantly increased in south Durban among participants with the GSTM1pos, GSTM1null, and the GSTP1AG+GG genotypes. The expression of GSTM1 and GSTP1 polymorphic genotypes may lead to varying susceptibility to the adverse effects of pollutants by modifying the response to oxidative stress. Key words: Glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase pi gene(GSTP1), oxidative stress, birth cohort, glutathione, gene polymorphism, DNA damage.