Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: An updated meta‐analysis of case–control studies

Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta‐analyses have reported inconclusive results. Therefore, an updated meta‐analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant ‘null’ genotype was compared with wild‐type ‘present’ in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case–control studies were suitable for inclusion in the meta‐analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192–1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293–2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051–1.781) and adults (OR = 1.859; 95% CI: 1.183–2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204–4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018–1.667), Africa (OR = 2.175; 95%CI: 1.560–3.031) and Latin America (OR = 2.265; 95%CI: 1.375–3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101–4.025) and Russian (OR = 2.747; 95% CI: 1.071–7.046) populations. This meta‐analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma.     

Phase I and II enzyme polymorphisms as risk factors for Barrett's esophagus and esophageal adenocarcinoma: a systematic review and meta‐analysis

Although several studies have examined the association between phase I/II enzyme polymorphisms and esophageal adenocarcinoma (EAC) and/or Barrett's esophagus (BE), their overall findings remain unclear. We performed a systematic review and meta‐analysis to determine whether phase I/II polymorphisms are independent risk factors for either BE or EAC. We employed keyword searches in multiple databases to identify studies published before October 1, 2007. Single‐nucleotide polymorphisms (SNPs) examined in ≥3 studies were meta‐analyzed to obtain a pooled estimate of effect. Meta‐analysis suggested the minor allele for GSTP1 Val¹⁰⁵ conveys modest excess risk (odds ratio [OR]_BE= 1.50, 95% confidence interval [CI] 1.16–1.95; OR_EAC= 1.20, 95% CI 0.94–1.54). No excess risk was observed with GSTM1 null (OR_BE= 0.77, 95% CI: 0.56–1.08; OR_EAC= 1.08, 95% CI: 0.79–1.48), GSTT1 null (OR_BE= 1.35, 95% CI: 0.91–2.01; OR_EAC= 0.84, 95% CI: 0.48–1.49), or CYP1A Val⁴⁶² (OR_EAC= 0.89, 95% CI: 0.40–1.97). Insufficient data existed to meta‐analyze remaining SNPs. Our review identified GSTP1_Ile105Val as a possible risk factor for BE and EAC in Caucasian males. No excess risk was observed for other phase I/II polymorphisms with sufficient data to meta‐analyze. Additional studies are needed to determine if GSTP1 conveys excess risk in females or non‐Caucasians and to evaluate other phase I/II polymorphisms.     

Influence of glutathione S‐transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug‐induced hepatotoxicity in a Caucasian population

Objectives: Genetic variations in enzymes of isoniazid metabolism confer an increased risk for antituberculosis drug‐induced hepatotoxicity in Asian populations. The present study was aimed at investigating the possible association of antituberculosis drug‐induced hepatotoxicity with polymorphisms at the glutathione S‐transferase (GST) gene in a Caucasian population. Methods: A prospective case–control study was nested in a cohort of patients with active tuberculosis who were treated with a combination of isoniazid, rifampicin and pyrazinamide. Cases constituted patients with antituberculosis drug‐induced hepatotoxicity (n=35), and controls constituted patients without any evidence of this complication (n=60). Homozygous null polymorphisms at GST loci M1 and T1 were analysed from genomic DNA from all participants. Results: The GSTT1 homozygous null polymorphism was significantly associated with antituberculosis drug‐induced hepatotoxicity [odds ratio (OR) 2.60, 95% confidence interval (CI) 1.08–6.24, P=0.03]. No significant association was observed between the GSTM1 homozygous null polymorphism and antituberculosis drug‐induced hepatotoxicity (OR 0.73, 95% CI 0.31–1.73, P=0.48). Conclusion: The GSTT1 homozygous null polymorphism may be a risk factor of antituberculosis drug‐induced hepatotoxicity in Caucasians.     

Glutathione-S-transferase （GSTM1, GSTrl） and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, large-scale case-control study including 2213 GCs, 1829 CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using real-time PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls. Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Common polymorphic deletion of glutathione S‐transferase theta predisposes to acquired aplastic anemia: Independent cohort and meta‐analysis of 609 patients

Acquired aplastic anemia (AA) is a rare life‐threatening bone marrow failure syndrome, caused by autoimmune destruction of hematopoietic stem and progenitor cells. Epidemiologic studies suggest that environmental exposures and metabolic gene polymorphisms contribute to disease pathogenesis. Several case–control studies linked homozygous deletion of the glutathione S‐transferase theta (GSTT1) gene to AA; however, the role of GSTT1 deletion remains controversial as other studies failed to confirm the association. We asked whether a more precise relationship between the GSTT1 null polymorphism and aplastic anemia could be defined using a meta‐analysis of 609 aplastic anemia patients, including an independent cohort of 67 patients from our institution. We searched PubMed, Embase, and the Cochrane Database for studies evaluating the association between GSTT1 null genotype and development of AA. Seven studies, involving a total of 609 patients and 3,914 controls, fulfilled the eligibility criteria. Meta‐analysis revealed a significant association of GSTT1 null genotype and AA, with an OR = 1.74 (95% CI 1.31–2.31, P < 0.0001). The effect was not driven by any one individual result, nor was there evidence of significant publication bias. The association between AA and GSTT1 deletion suggests a role of glutathione‐conjugation in AA, possibly through protecting the hematopoietic compartment from endogenous metabolites or environmental exposures. We propose a model whereby protein adducts generated by reactive metabolites serve as neo‐epitopes to trigger autoimmunity in aplastic anemia. Am. J. Hematol. 88:862–867, 2013. © 2013 Wiley Periodicals, Inc.     

Glutathione-S-transferase (GSTM1, GSTT1) and the risk of gastrointestinal cancer in a Korean population

AIM: To evaluate the association of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) null genotypes with the risk of gastric cancer (GC) and colorectal cancer (CRC) in a South Korean population.METHODS: We conducted a population-based, largescale case-control study including 2213 GCs, 1829CRCs, and 1699 controls. Null and non-null genotypes of GSTM1 and GSTT1 were determined using realtime PCR.RESULTS: The null genotypes of GSTM1 and GSTT1 were not significantly associated with elevated risk of gastric (OR = 1.070, 95% CI = 0.935-1.224; OR = 1.101, 95% CI = 0.963-1.259, respectively) or colorectal cancer (OR = 1.065, 95% CI = 0.923-1.228; OR = 1.041, 95% CI = 0.903-1.200, respectively). The frequency of the combined null GST genotype was not different between the two cancer groups and controls.Moreover, smoking, drinking, and age did not modify the association between these genotypes and the risk of gastric or colorectal cancer.CONCLUSION: GSTM1 and GSTT1 null genotypes were not associated with increased risk of GC or CRC in Koreans.     

Potentially functional COX‐2 −1195G>A polymorphism increases the risk of digestive system cancers: A meta‐analysis

Background and Aim: Three potentially functional polymorphisms: ?765G>C, ?1195G>A, and 8473T>C in the cyclooxygenase‐2 (COX‐2) gene were identified and proposed to be associated with cancer susceptibility. The aim of this meta‐analysis was to evaluate the association between these three polymorphisms and the risk of cancer in diverse populations. Methods: All case‐control studies published up to November 2009 on the association between the three polymorphisms of COX‐2 and cancer risk were identified by searching PubMed. The cancer risk associated with the three polymorphisms of the COX‐2 gene was estimated for each study by OR together with its 95% confidence interval (CI), respectively. Results: A total of 47 case‐control studies were included, and variant genotypes GA/AA of ?1195G>A were associated with a significantly increased cancer risk (GA/AA vs GG: odds ratio [OR], 1.29; 95% CI, 1.18–1.41; P_{heterogeneity} = 0.113), and this significant association was mainly observed within cancers of the digestive system (e.g. colorectal, gastric, esophageal, oral, biliary tract, gallbladder, and pancreatic) without between‐study heterogeneity (GA/AA vs GG: OR, 1.36; 95% CI; 1.23–1.51; P_{heterogeneity} = 0.149). Furthermore, a stratification analysis showed that the risk of COX‐2?1195G>A associated with cancers in the digestive system was more evident among Asians than Caucasians. However, for COX‐2?765G>C and 8473T>C, no convincing association between the two polymorphisms and risk of cancer or cancer type was observed. Conclusions: The effect of three potentially functional polymorphisms (?765G>C, ?1195G>A, and 8473T>C) in the COX‐2 gene on cancer risk provided evidence that the COX‐2?1195G>A polymorphism was significantly associated with increased risk of digestive system cancers, especially among Asian populations.     

Association between the tumour necrosis factor-α-308G/A polymorphism and chronic obstructive pulmonary disease: an update

Background and objective: Previous studies have suggested that the ?308A allele in the tumour necrosis factor‐α (TNF‐α) gene promoter (rs1800629) may be a potential risk factor for COPD. However, more recent findings have been inconsistent. In the present study, a meta‐analysis was performed to assess the association between the TNF‐α?308G/A single nucleotide polymorphism (SNP) and the risk of COPD. Methods: Published studies were retrieved from PubMed, EMBASE and other databases. All studies assessing the association between the TNF‐α?308G/A SNP and the risk of COPD were assessed. Pooled ORs with 95% CIs were calculated. Results: In the 36 studies that met the inclusion criteria, 4975 patients and 6518 control subjects had been genotyped. The overall results showed that the association between the TNF‐α?308G/A SNP and the risk of COPD was statistically significant for Asians (OR = 2.36, 95% CI: 1.84–3.02, P < 0.0001) but not for Caucasians (OR = 1.07, 95% CI: 0.91–1.25, P = 0.438). As smoking is one of the most important risk factors for COPD, a second meta‐analysis that included only smokers (3018 patients and 2749 control subjects) was performed. This analysis confirmed that the association between the TNF‐α?308G/A SNP and COPD was statistically significant for Asians (OR = 1.72, 95% CI: 1.14–2.61, P = 0.011) but not for Caucasians (OR = 1.16, 95% CI: 0.86–1.56, P = 0.33). Conclusions: This meta‐analysis suggests that the TNF‐α?308A genotype is associated with an increased risk of COPD in Asian but not Caucasian populations. Further studies are necessary to evaluate the relationship between TNF‐α polymorphisms and the risk of COPD.     

Association between combinations of glutathione‐S‐transferase M1, T1 and P1 genotypes and non‐alcoholic fatty liver disease

Background/Aims: Glutathione‐S‐transferases (GSTs) play a crucial role in antioxidant defence mechanisms, by detoxifying xenobiotics and by inactivating endogenous byproducts of oxidative stress. Functional failure, as a sequel of an altered GST genotype, may thus aggravate non‐alcoholic fatty liver disease (NAFLD). This study investigated whether the GSTs genotypes could affect the risk for NAFLD. Methods: A cross‐sectional case–control analysis included 253 Japanese participants in a health screening programme. The GSTM1 null, GSTT1 null and GSTP1 Ile105Val variant genotypes were determined as putative high‐risk genotypes. Results: The incidence of NAFLD was 27.3%. The frequency of the GSTM1 null genotype was higher in NAFLD than in the control [adjusted odds ratio (OR), 2.00; 95% confidence intervals (CI), 1.01–3.95]. Moreover, any combination of two putative high‐risk genotypes exhibited a higher risk for NAFLD with an adjusted OR from 3.52 (95% CI, 1.08–11.43)–4.01 (95% CI, 1.28–12.56). However, the significance for the combination of GSTM1 null and GSTT1 null genotypes only remained after Bonferroni's correction. In addition, the risk for NAFLD increased as the number of high‐risk genotypes, and the OR among three high‐risk genotypes carriers was 9.67 (95% CI: 1.61–58.26). Conclusion: This is the first report to show the impact of the GSTs genotypes on the development of NAFLD. This finding, which should be confirmed in further studies in larger populations, may help to develop a more targeted prevention programme at an early stage for subjects with an increased risk for NAFLD.     

Association between maternal body mass index and congenital heart defects in infants: A meta‐analysis

We conducted this meta‐analysis to address the open question of a possible association between maternal body mass index (BMI) and congenital heart defects (CHDs) in infants. We conducted a comprehensive computerized search of PubMed, Web of Science, Medline, and Embase databased (January 1980 through August 2017). We assessed the association between maternal BMI and the risk for congenital heart defects in their offspring. Study‐specific relative risk estimates were polled according to random‐effect or fixed‐effect models. From 2567 citations, a total of 13 case‐control studies and 4 cohort studies were selected for a meta‐analysis, including more than 1 150 000 cases. The pooled odds radio (OR) of 1.065 (95% confidence interval [CI], 1.021‐1.100; P = .001; I²= 60.1%) indicated a positive effect of maternal overweight status (BMI 25.0–29.9 kg/m²) on the risk for congenital heart defects in infants. Moreover, we observed a significant association between maternal obesity (BMI ≥ 30 kg/m²) and congenital heart defects in their offspring (OR: 1.174; 95% CI, 1.146–1.203, P = 0.161; I² =25.5%). However, there was little significant evidence of an association between maternal underweight status (BMI < 18.5 kg/m²) and offspring with congenital heart defects, and the pooled OR was 1.015 (95% CI, 0.980–1.052; P = 0.085; I²=34.0%). Our meta‐analysis provides robust evidence of the positive association between maternal BMI and the risk for fetal congenital heart defects.     

GSTT1 (rs4025935) null genotype is associated with increased risk of sickle cell disease in the populations of Tabuk—Northwestern region of Saudi Arabia

Background: Glutathione system plays an important role in the protection of cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphism of GST genes may increase the risk and severity of sickle cell disease (SCD). Present study was, therefore, undertaken to examine the relative impact of the genetic polymorphism of GSTT1 and GSTM1 (rs4025935 and rs71748309) on susceptibility and hematological aspects of the patients with SCD.

Methods: Present study included 100 patients with SCD and 200 healthy controls from northwestern region of Saudi Arabia. GSTM1 and GSTT1 (rs4025935 and rs71748309) genotypes were investigated by using single-tube multiplex PCR technique.

Results: It was observed that patients with SCD possessed significantly higher frequency of GSTT1 null genotype (26%) than healthy controls (15%), (P?=?0.00001). Compared to the presence of GSTT1 genotype, the OR for the GSTT1 null genotype were estimated to be 4.3 (2.17–8.64, P?=?0.00001). However, such association was not observed with respect to the presence of GSTM1 null genotype. In addition, it was observed that SCD in patients with GSTT1 genotype, the mean percentage levels for HbF and HbS were 0.48 and 35.4%, respectively; however, among SCD patients with GSTT1 null genotype, the mean percentage levels were significantly higher 1.62% (P?=?0.004) and 39.38% (P?=?0.02), respectively.

Conclusion: GSTT1 null genotype is significantly associated with increased risk of SCD among the population of northwestern region of Saudi Arabia. In addition, it may be one of the important factors responsible for hematological manifestations of SCD.     

Body weight gain and risk of colorectal cancer: a systematic review and meta‐analysis of observational studies

While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta‐analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between‐study heterogeneity was assessed using I² statistics. Overall, the summary RR (95% CI) was 1.22 (1.14–1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I² = 21.2%). In a dose‐response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%–5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.     

Meta‐analysis of alcohol consumption and risk of extrahepatic bile system cancer

Aim: Alcohol consumption increases the risk of liver cancer. However, there is still controversy regarding alcohol consumption and the risk of extrahepatic bile system cancer (EBSC). We performed a meta‐analysis to provide an overview of the relevant studies and gain more robust estimates of the relationship between alcohol consumption and risk of EBSC. Methods: Relevant studies published between January 1966 and October 2010 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between alcohol consumption and risk of EBSC was assessed by adjusted odds ratio (OR). Results: A total of 113 767 participants from 10 studies (nine case–control studies and one cohort study) were identified in this meta‐analysis. The studies provided adjusted overall OR estimates for drinkers versus non‐/low drinkers, leading to a pooled adjusted OR of 0.82 (95% confidence interval [CI] = 0.72–0.94, P for heterogeneity = 0.194, I² = 27.2%). The overall adjusted OR of hospital‐based studies and population‐based studies were 0.80 (95% CI = 0.65–0.99, P = 0.260) and 0.79 (95% CI = 0.64–0.98, P = 0.119), respectively. For the heavy drinkers, the adjusted OR significance increased to 1.58 (95% CI = 0.97–2.57, P for heterogeneity = 0.055, I² = 65.4%), but it had no statistical significance. Conclusion: There is evidence that moderate alcohol consumption lowers the risk of EBSC compared with non‐/low alcohol consumption, but not heavy alcohol consumption. Further multicenter and better controlled studies are required to confirm these findings.     

Meta-analysis of association between GSTM1 gene polymorphism and cervical cancer

ObjectiveTo investigate association between glutathione S-transferases (GSTs) and cervical cancer.MethodsPublished literature from PubMed, EMBASE, and other databases were retrieved. All studies evaluating the association between GSTM1/GSTT1 polymorphisms and cervical were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model.ResultsA total of 15 case-control studies were included in the meta-analysis of GSTM1 genotypes (1 825 cases and 2 104 controls). The overall result showed that the association between GSTM1 null genotype and risk for cervical cancer was statistically significant (OR=1.53, 95%CI=1.18–2.00). Great heterogeneity was found between studies. Subgroup analysises were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had higher risk of cervical cancer (OR=1.56, 95%CI=1.01–2.41). For the ethnicity stratification, significant increased risk of null GSTM1 genotype was found in Chinese and Indian population, but no increased risk in other population.ConclusionsThis meta-analysis provides strong evidence that the GSTM1 null genotype is associated with the development of cervical cancer, and especially in Chinese and Indian population, and smoking shows a modification on the association between GSTM1 null genotype and cervical cancer.     

APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ² tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m² (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m² (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.     

GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis

Glutathione S-transferases (GSTs) contribute to the metabolism of different xenobiotics and anticancer drugs and confer protection against oxidative stress thus may influence the treatment outcome of acute myeloid leukemia (AML). Studies regarding the association between GSTT1 and GSTM1 polymorphisms and treatment outcome in AML patients showed an inconsistent result. A systematic review and meta-analysis were performed to further explore this association. PubMed, Hartford User Group Exchange (HUGE), and China National Knowledge Infrastructure (CNKI) databases were searched for all related publications. Statistical analyses were analyzed by using RevMan 5.0 and Stata 9.0 softwares. A total of 1,837 patients in 11 studies were included. GSTT1 null genotype was found to be significantly associated with a reduced response after first course of induction chemotherapy (odds ratio (OR)?=?0.894, 95 % confidence interval (CI)?=?0.818–0.977, P?=?0.013), progression-free survival (PFS; hazard ratio (HR) = 0.698, 95 % CI?=?0.520–0.937, P?=?0.017), and overall survival (OS; HR?=?0.756, 95 % CI?=?0.618–0.925, P?=?0.007) in Asian population. GSTM1/GSTT1 double-null genotype was also identified to be significantly associated with response after the first course of induction chemotherapy (OR?=?0.40, 95 % CI?=?0.24–0.67, P?=?0.0003). Our study suggested that GSTT1 null genotype and GSTT1/GSTM1 double-null genotype were associated with a worse treatment outcome for AML patients, especially in Asian population.     

Polymorphisms of drug‐metabolizing genes and risk of non‐Hodgkin lymphoma

Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug‐metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non‐Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population‐based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)_AG = 0.67, 95% confidence interval (CI) = 0.55–0.82; OR_AG/GG = 0.66, 95% CI = 0.54–0.80) and DLBCL (OR_AG = 0.63, 95% CI = 0.49–0.82; OR_AG/GG = 0.64, 95% CI = 0.50–0.82). For T‐cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (OR_AG/GG = 0.65, 95% CI = 0.44–0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (OR_AG = 1.28, 95% CI = 1.07–1.54; OR_AG/GG = 1.26, 95% CI = 1.06–1.51) and DLBCL (OR_AG = 1.32, 95% CI = 1.04–1.66; OR_AG/GG = 1.30, 95% CI = 1.03–1.63), but not T‐cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Lack of association of Toll-like receptor 9 polymorphisms with susceptibility to systemic lupus erythematosus in an Asian population: a meta-analysis

Abstract

The association of Toll-like receptor 9 (TLR9) gene polymorphisms with systemic lupus erythematosus (SLE) risk remains controversial and ambiguous. To more precisely estimate the relationship between TLR9 gene polymorphisms and the susceptibility to SLE, a meta-analysis was performed. A total of seven independent studies were involved in this analysis. Meta-analysis was performed for three TLR9 gene polymorphisms (rs187084, rs352139, and rs352140). We have compared allele or genotype frequencies of the polymorphisms in SLE patients and controls. When available studies were pooled into the meta-analysis, there was no evidence showing a significant association between rs187084 and SLE risk in an Asian population (for C vs. T: OR = 0.81, P = 0.117; for CC vs. TT: OR = 0.71, P = 0.158; for CT vs. TT: OR = 0.86, P = 0.085; for CC + CT vs. TT: OR = 0.78, P = 0.093; for CC vs. CT + TT: OR = 0.81, P = 0.285). Similar results were found between rs352139 and SLE. No significant association was detected in any genetic model in the Asian population either (for G vs. A: OR = 1.11, P = 0.095; for GG vs. AA: OR = 1.32, P = 0.238; for GA vs. AA: OR = 1.17, P = 0.084; for GG + GA vs. AA: OR = 1.17, P = 0.073; for GG vs. GA + AA: OR = 1.17, P = 0.404). We found no association between TLR9 gene rs352140 polymorphism and SLE in the Asian population (for A vs. G: OR = 1.02, P = 0.728). In conclusion, there is still not enough evidence to indicate an association between TLR9 gene rs187084, rs352139, and rs352140 polymorphisms and the development of SLE in the Asian population.     

Elevated risk of colorectal cancer associated with the AA genotype of the cyclin D1 A870G polymorphism in an Indian population

Purpose: To investigate whether the common cyclin D1 (CCND1) A870G polymorphism is a risk factor for colorectal cancer (CRC) in an Indian population. Methods: In this study, 301 newly diagnosed CRC patients and 291 healthy control subjects were genotyped by the PCR-RFLP method. Genotype frequencies were compared between cases and controls, and the association of genotypes with CRC was studied. Results: The CCND1 870 A allele was more frequently observed in CRC patients than controls (0.63 vs. 0.56, P=0.01), and after adjustment for age, sex, smoking habits, family history, family income and the consumption of meat, fish, vegetables and fruit, an increased risk was observed for the AA genotype compared to the GG+AG genotype (OR=1.56; 95% CI: 1.10–2.21). The increased risk were also found for colon (OR=1.96; 95% CI: 1.08–3.57) and rectal cancer (OR=1.51; 95% CI: 1.04–2.19). No correlation was observed between genotypes and age of diagnosis of CRC (49.9, 48.7 and 49.4 years for the GG, AG and AA genotypes, respectively; P=0.84). Multivariate analysis also revealed a stronger positive association with the AA genotype among patients with high meat intake (OR=2.67; 95% CI: 1.29–5.51), and particularly significant inverse associations with the GG+AG genotypes were also found for those with high vegetable consumption (OR=0.46; 95% CI: 0.27–0.79 of 2–3 servings/day, and OR=0.31; 95% CI: 0.18–0.53 for >3 servings/day) and fish intake (OR=0.48; 95% CI: 0.28–0.82). Conclusion: These data support the hypothesis that the CCND1 A870G polymorphism may increase the risk of CRC in our Indian population.     

Role of epoxide hydrolase 1 gene polymorphisms in esophageal cancer in a high‐risk area in India

Background and Aim: Microsomal epoxide hydrolase 1 (EPHX1) is involved in the metabolism of environmental and tobacco carcinogens. Tobacco smoking, betel quid chewing, and alcohol consumption are the major known risk factors for esophageal cancer. The present case‐control study evaluated the influence of EPHX1 genetic variations on esophageal cancer susceptibility in 142 patients and 185 healthy controls from a high‐incidence region of India where tobacco use and alcohol consumption are widespread and the users of these two substances are also betel quid chewers. Methods: EPHX1 polymorphic alleles (exon 3, Tyr113His and exon 4, His139Arg) were genotyped by polymerase chain reaction–restriction fragment length polymorphism method and direct sequencing. The results were analyzed using logistic regression to calculate odds ratios (OR) and confidence intervals (CI). Results: Patients with exon 4 genotypes (139His/Arg, 139Arg/Arg) and the 139Arg allele were significantly associated with a risk of esophageal cancer (OR_His139Arg 1.887, 95% CI = 1.112–3.201, P = 0.019; OR_Arg139Arg 7.140, 95% CI = 1.276–393.953, P = 0.025 and OR_Arg 1.83, 95% CI = 1.19–2.82, P = 0.003). The 139His/Arg genotype was a significant risk factor for esophageal cancer in tobacco chewers and betel quid chewers. Patients with the 139Arg/Arg genotype were at significantly higher risk for developing a well‐differentiated and moderately‐differentiated grade of tumor. In contrast, the 113His/His genotype of exon 3 was a significant protective factor for esophageal cancer in tobacco smokers (OR 0.291, 95% CI = 0.138–0.616, P = 0.001), betel quid chewers (OR 0.434, 95% CI = 0.236–0.797, P = 0.007), and alcohol users. Conclusion: EPHX1 exon 4 139His/Arg, and 139Arg/Arg genotypes were associated with a higher risk of esophageal cancer in a high‐risk area of India.