Correlation between LSP1 polymorphisms and the susceptibility to breast cancer

Objective: The present study aimed at assessing the relationship between Leukocyte-specific protein 1 gene (LSP1) polymorphisms (rs569550 and rs592373) and the pathogenesis of breast cancer (BC). Methods: 70 BC patients and 72 healthy subjects were enrolled in the study. Rs569550 and rs592373 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) with 95% confidence interval (CI) were calculated by the chi-squared test to assess the relationship between LSP1 polymorphisms and BC risk. Linkage disequilibrium (LD) and haplotypes were also analyzed by HaploView software. Results: Genotype distribution of the control was in accordance with Hardy-Weinberg equilibrium (HWE). The homozygous genotype TT and T allele of rs569550 could significantly increase the risk of BC (TT vs. GG: OR=3.17, 95% CI=1.23-8.91; T vs. G: OR=1.63, 95% CI=1.01-2.64). For rs592373, mutation homozygous genotype CC and C allele were significantly associated with BC susceptibility (CC vs. TT: OR=4.45, 95% CI=1.38-14.8; C vs. T: OR=1.70, 95% CI=1.03-2.81). LD and haplotypes analysis of rs569550 and rs592373 polymorphisms showed that T-C haplotype was a risk factor for BC (T-C vs. G-T: OR=1.74, 95% CI=1.04-2.92). Conclusion: LSP1 rs569550 and rs592373 polymorphisms are both risk factors for BC.     

中国人群细胞色素P4501A1基因MSPⅠ位点联合GSTM基因多态性与肺癌易感性的荟萃分析

目的 用荟萃(Meta)分析探讨中国人群细胞色素P4501A1 (CYP1A1)基因MSP Ⅰ位点联合GSTM基因位点多态性对肺癌的形成作用。方法 制定文献纳入和排除标准,双人独立全面检索相关文献,根据纳入标准列出不同基因型组合的个体发生肺癌的优势比（OR）值和95％可信区间(CI),进行异质性检验并根据异质性检验结果采用不同的模型（固定效应模型、随机效应模型）合并OR值、95％CI和P值。结果共纳入12篇文献,涉及13个人群,以CYP1A1基因(w/w)、GSTM基因(+)为参照,CYP1A1基因(w/m)、GSTM基因(+),CYP1A1基因(m/m)、GSTM基因(+),CYP1A1基因(wlw)、GSTM基因（-）,CYP1A1基因(w/m)、GSTM基因（-）,CYP1A1基因(m/m)、GSTM基因（-）的发生肺癌的风险合并值OR及95％CI分别为(1.22,0.95～1.57),(1.24,0.88～1.76),(1.51,1.07～2.12),(1.82,1.30～2.54),(2.06,1.56～2.72)。结论 CYP1A1基因突变型（杂合子和纯合子）联合GSTM基因缺失型可显著增加个体的肺癌发生风险,在肺癌筛检过程中要重视对基因型的筛查,做好一级预防。     

Genetic polymorphisms of CYP2D6, GSTM1, and GSTT1 genes and bladder cancer risk in North India

The study consisted of 100 patients (97 males and 3 females) suffering from bladder cancer and 76 matching controls. The maximum number of patients in this study was in the age group of 61-70 years. The prevalence of genetic polymorphism in the CYP2D6, GSTM1, and GSTT1 genes has been investigated to find their association with risk of bladder cancer. While there was no association between the heterozygous (HEM) genotype of the CYP2D6 gene with the risk of bladder cancer [odds ratio (OR)=1.00; 95% confidence interval (CI)=0.46-2.16], it was 1.5-fold with poor metabolizers (PM) genotype. When stratified according to different grades of bladder cancer, a significant association was found with an OR=3.54 (95% CI=0.89-13.98) in grade II, 3.3 (95% CI=0.12-20.6) in grade III, and 1.67 (95% CI=0.15-18.45) in grade IV. When stratified in relation to smoking status, significant association of the disease was found in heavy smokers with an OR=2.13 (95% CI=0.71-6.43). Subjects with the null genotype for GSTM1 had a slightly significant association with the bladder cancer risk and the risk increased to 2-fold with the GSTT1 null genotype. Smoking status also revealed an impact on the prevalence of bladder cancer in the individuals with GSTM1 and GSTT1 null genotypes. The results indicated that there is a 3-fold increase in risk of developing this cancer in the presence of one copy of the variant CYP2D6 (HEM) allele and null GSTT1.     

Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia

Infection with high-risk human papillomavirus (HPV) plays a major role in the etiology of cervical cancer (CC). However, most infected women do not develop cancer. Therefore, exposure to other carcinogenic agents may be a contributing risk factor for CC. We investigated the hypothesis that environmental exposure to cigarette smoke and inheritance of polymorphic chemical metabolizing genes (CYP2E1, GSTM1, and mEH) significantly increase the risk for neoplasia. We selected 76 cases with high-grade cervical neoplasia or with invasive CC and 75 matched healthy controls. The collected data support the well-established observation that infection with high-risk HPV is the major risk factor for CC (OR = 75; 95% CI = 26-220). In addition, our data show that women who smoked more than 15 "pack-year" had a significant 6.9-fold increase in risk (95% CI = 1.2-40.3) after adjustment for HPV infection. The CYP2E1 variant genotype did not significantly increase the risk for neoplasia. A significant increase in risk for neoplasia was observed for the low-activity mEH 113 His allele after adjustment for smoking (OR = 3.0; 95% CI = 1.4-6.3). The GSTM1 null genotype was associated with a significant 3.3-fold increased risk for neoplasia (95% CI = 1.0-11.8) compared to women who were GSTM1-positive after adjustment for smoking and HPV infection. Our study suggests that genetic differences in the metabolism of cigarette smoke, particularly GSTM1, may confer susceptibility to CC. Further studies using larger populations will be needed to confirm our observations and to validate data for disease prevention.     

Tankyrase 1 polymorphism associated with an increased risk in developing non-small cell lung cancer in a Chinese population: a proof-of-principle study

Objectives: Tankyrase 1 (TNKS1), a poly (ADP-ribose) polymerase, regulates telomere length and apoptosis in cells, overexpression of which occurred in non-small cell lung cancer (NSCLC). This study investigated TNKS1 single-nucleotide polymorphisms (SNPs) for association with a risk in NSCLC development in a Chinese population. Methods: NSCLC cases and healthy controls of 500 each were recruited for genotyping of 24 TNKS1 SNPs. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Haploview software was to analyze association between haplotypes and NSCLC risk. Results: TNKS1 rs6601328 A allele was associated with a lower risk in developing NSCLC and adenocarcinoma (ADC) (OR=0.71; 95% CI, 0.51-0.99 and OR=0.70; 95% CI, 0.50-0.99), whereas TNKS1 rs11991621 C allele (OR=1.44; 95% CI, 1.03-2.03), rs11991621 C/C (OR=1.44, 95% CI, 1.03-2.35; P=0.03), and rs10503380 G/G (OR= 1.56, 95% CI, 1.09-2.50, P=0.02) were associated with a higher risk in developing NSCLC or ADC in females and rs6601328 A/A major allele (OR=1.39; 95% CI, 1.00-1.92; P=0.047) and rs7015700 G/G (OR= 1.51, 95% CI, 1.04-2.21) was associated with an increased NSCLC or ADC risk in males but a reduced NSCLC risk (OR=0.63; 95% CI, 0.42-0.96) and ADC risk (OR=0.64; 95% CI, 0.42-0.97) in females. Haploview showed that there were three Haplotype Blocks associated with NSCLC risk. However, TNKS1 rs12541709 C/C was associated with protective effect against ADC (OR=0.75; 95% CI, 0.56-0.99; P=0.04) in this Chinese population. Conclusion: TNKS1 SNPs (rs11991621 rs10503380, and rs7015700) were associated with NSCLC risk, whereas rs6601328 and rs12541709 inversely associated with NSCLC or ADC risk in this Chinese population.     

Association between Promoter Polymorphisms of TFF1, TFF2, and TFF3 and the Risk of Gastric and Diffuse Gastric Cancers in a Korean Population

Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.

Graphical Abstract

相似文献   

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South 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. As the incidence of lung cancer is known to differ according to ethnicity, we have conducted a case-control study of 146 South Indian lung cancer patients along with 146 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. The current weight of evidence from our study indicated that the frequency of CYP1A1 MspI homozygous variant alleles was significantly higher in cases (OR=3.178). We observed a considerable difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=2.472, 95% CI: 1.191–5.094, P=0.014). There was no relative risk in GSTM1 null genotype when analysed singly (P=0.453). Considering genotype combinations, risk of lung cancer increased remarkably significantly in individuals having one variant allele of CYP1A1, GSTM1, or GSTT1, suggesting gene–gene interactions. Rare genotypic combinations (such as CYP1A1 wild GSTM1 or GSTT1 either null; CYP1A1 variant both GSTM1 and GSTT1 present; CYP1A1 variant GSTM1 or GSTT1 either null), were at higher risk compared to the reference group. Moreover, patients who had smoked <20 pack years and harboured the CYP1A1 variant allele or the GSTT1 null genotype also had a significant risk of lung cancer. Hence our study—the first to analyse a South Indian population—suggests the importance of combined CYP1A1, GSTM1 and GSTT1 polymorphisms in the development of smoking-induced lung cancer.     

Genetic and environmental interactions on oral cancer in Southern Thailand

Many countries are interested in understanding the relationship between genetic susceptibility and their prevalent environmental cancers for disease prevention. In Thailand we conducted a population-based case-control study of 53 matched pairs to assess the risk of oral cancer in relation to genetic polymorphism of the glutathione-S-transferase genes (GSTM1 and GSTT1) in cigarette smokers, alcohol drinkers, and betel quid chewers. Interaction of the genes with other potential risk factors such as local bean consumption were also elucidated. Homozygous deletion of GSTM1 has a frequency of 56.6% (n = 30 over 53) among the patients and 30.2% (16/53) among the controls. This gene is associated with a 2.6-fold higher risk for development of oral cancer (95% CI 1.04-6.5). Among the null GSTM1 individuals, those who smoke, consume alcohol, and/or chew betel quid have a significantly increased risk for oral cancer with an odd ratio (OR) = 4.0 (95% CI = 1.2-13.7), OR = 7.2 (95% CI = 1.5-33.8), and OR = 4.4 (95% CI = 1.1-17.8), respectively. Interactions between any two of the lifestyle habits for oral cancer risk, however, are not found. The frequency of the GSTT1 null genotype is 34.0% (18/53) among the patients and 47.2% (25/53) among our controls. There is no association between the GSTT1 null allele and oral cancer risk. In conclusion, our study provides data to indicate that individuals who have homozygous deletion of the GSTM1 gene have increased risk for oral cancer. The risk increases further when these individuals are exposed to environmental toxicants such as chemicals in cigarette smoke, alcohol, and betel quid. These baseline data can be applied to a larger population-based study, both to verify the observation and to conduct mechanistic investigations.     

Correlation between survivin genetic polymorphisms and lung cancer susceptibility

Aims: The purpose of the study was to analyze the relationship of survivin polymorphisms including -31G/C, -625G/C, 9194A/G and 9809T/C with the susceptibility to lung cancer. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the polymorphisms of -31G/C, -625G/C, 9194A/G and 9809T/C in 104 patients with lung cancer and 104 healthy controls. Then, linkage disequilibrium and haplotypes were analyzed by HaploView software. The differences of genotype, allele and haplotype frequencies in case and control group were assessed via chi-square test. Odds ratio (OR) with 95% CI were used to evaluate the correlation of survivin polymorphisms with lung cancer. Results: Genotype distribution of each polymorphism site in control group was in agreement with Hardy-Weinberg equilibrium (HWE) (P>0.05). The frequency of -31G/C CC genotype and C allele in case group were much higher than that of controls, respectively (CC: 33.6% vs. 22.1%; C: 57.2% vs. 46.6%) and CC genotype as well as C allele were appeared to be risk factors for lung cancer. Meanwhile, 9194A/G GG genotype could increase the risk for lung cancer (OR=2.86, 95% CI=1.14-7.20). The risk of G allele carriers for lung caner was higher than that of A allele (OR=1.63, 95% CI=1.08-2.47). The haplotypes analysis indicated that CGGC and GCAT were associated with the susceptibility to lung cancer (OR=2.79, 95% CI=1.58-4.92; OR=2.36, 95% CI=1.29-4.30). Conclusions: Survivin -31G/C and 9194A/G polymorphisms were associated with the risk of lung cancer. The CGGC and GCAT haplotypes carriers were more likely to develop lung cancer.     

Impact of glutathione S-transferase M1 and T1 gene polymorphisms on the smoking-related coronary artery disease

Glutathione S-transferase (GST) plays a key role in the detoxification of xenobiotic atherogen generated by smoking. To analyze the effect of GSTM1/T1 gene polymorphisms on the development of smoking-related coronary artery disease (CAD), 775 Korean patients who underwent coronary angiography were enrolled. The subjects were classified by luminal diameter stenosis into group A (>50%), B (20-50%), or C (<20%). GSTM1 and GSTT1 gene polymorphisms were analyzed using multiplex polymerase chain reaction (PCR) for GSTM1/T1 genes and CYP1A1 gene for internal control. Of 775 subjects, 403 patients belonged to group A. They had higher risk factors for CAD than group B (N=260) and group C (N=112). The genotype frequencies of null GSTM1 and GSTT1 showed no significant differences among 3 groups. Considering the effect of GSTM1 gene polymorphisms on the smoking-related CAD, smokers with GSTM1 null genotype had more increased risk for CAD than non-smoker with GSTM1 positive genotype (odds ratios [OR], 2.07, confidence interval [CI], 1.06-4.07). Also the effect of GSTT1 gene polymorphism on smoking-related CAD showed the same tendency as GSTM1 gene (OR, 2.00, CI, 1.05-3.84). This effect of GSTM1/T1 null genotype on smoking-related CAD was augmented when both gene polymorphisms were considered simultaneously (OR, 2.76, CI, 1.17-6.52). We concluded that GSTM1/T1 null genotype contributed to the pathogenesis of smoking-related CAD to some degree.     

Gender-specific effects of NAT2 and GSTM1 in bladder cancer

One approach for risk assessment of cancer is the evaluation of polymorphic enzymes involved in cancer using molecular tools. Phase II enzymes are involved in the detoxification of several drugs, environmental substances and carcinogenic compounds. Here, we analyzed enzymes for their putative relevance in urinary bladder cancer. The hereditable enzyme polymorphism of arylamine N-acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) was studied in 157 hospital-based patients and in 223 control subjects. Slow acetylation was not observed to be a significant risk factor of developing bladder cancer (OR: 1.33; 95% CI 0.85-2.09). One genotype responsible for slow acetylation (NAT2*5B/*6A) was observed significantly more frequently in bladder cancer patients compared with control subjects (OR: 1.63; 95% CI 1.03-2.58). Gender-specific effects were observed when patients were divided into subgroups. In male patients, slow acetylators were identified as carrying a significant increased risk of developing bladder cancer, in particular when the genotype NAT2*5B/*6A was combined with the GSTM1 null genotype (OR: 4.39; 95% CI 1.98-9.74). By contrast, the same genotype combination significantly protected female patients from bladder cancer (OR: 0.21; 95% CI 0.06-0.80).     

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.     

Glutathione S-transferase P1 Ile105Val Polymorphism and Oral Cancer Risk: A Meta-Analysis

Objective The glutathione S-transferase P1 (GSTP1) gene has been suggested to play an important role in the pathogenesis of oral cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of GSTP1 Ile105Val polymorphisms with oral cancer risk.Methods Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.Results 13 studies (1803 oral cancer cases and 2998 controls) for GSTP1 Ile105Val polymorphism were included in the meta-analysis. The results indicated that there was no significant association between GSTP1 Ile105Val polymorphism and oral cancer in the overall population (OR=1.30, 95%CI=0.92-1.38, I²=48.0%, p for heterogeneity=0.027). Further subgroup analysis by ethnicity suggested that GSTP1 Ile105Val polymorphism was significantly associated with oral cancer only in East Asians (OR=1.64, 95%CI=1.16-2.31, I²=0.0%, p for heterogeneity=0.525), but not in Caucasians (OR=1.16, 95%CI=0.73-1.82, I²=7.5%, p for heterogeneity=0.299), Africans (OR=1.10, 95%CI=0.37-3.28), South Asians (OR=1.20, 95%CI=0.69-2.08, I²=74.3%, p for heterogeneity=0.021) and mixed population (OR=0.91, 95%CI=0.70-1.20, I²=39.7%, p for heterogeneity=0.174).Conclusions The present meta-analysis has limited evidence to support the association of GSTP1 Ile105Val polymorphism with HCC risk in the overall population. However, GSTP1 Ile105Val polymorphism might be associated with risk of oral cancer in East Asians.     

CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population.     

Genetic polymorphisms in the cytochrome P450 1A1, glutathione S-transferase M1 and T1, and susceptibility to colon cancer

Several polymorphic cytochrome P-450 and glutathione S-transferase (GST) enzymes are involved in the activation and detoxification of many potential carcinogens and may therefore be important in susceptibility to cancer induction. CYP1A1 MspI, GSTM1, and GSTT1 are polymorphic enzymes and some alleles have been correlated with an increased risk of developing some cancers. In the present study, we examined possible associations between genetic polymorphisms of CYP1A1 MspI, GSTM1, and GSTT1 and colon cancer in a United Kingdom population. An excess of CYP1A1 MspI, and GSTM1 null genotypes was observed amongst colon cancer patients, although this did not reach the level of statistical significance. We found no significant increase in the risk of colon cancer for either CYP1A1 MspI (OR = 1.39; 95%CI: 0.46-4.21) or GSTM1 null (OR = 1.41; 95%CI: 0.76-3.01) genotypes. Individuals with GSTT1 null genotype had no association with colon cancer (OR = 0.42; 95%CI: 0.09-2.02). No significant association was observed in the site of colon cancer (proximal vs. distal). This study suggests that the polymorphisms of CYP1A1 MspI, GSTM1, and GSTT1 are not associated with a significant risk of developing colon cancer in a United Kingdom population.     

Glutathione S-transferase M1 gene polymorphism in bladder cancer patients. a marker for invasive bladder cancer?

The glutathione S-transferase M1 (GSTM1) gene is polymorphic in humans, and the deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous absence of the GSTM1 gene, or the "null" genotype (GSTM1, 0/0). The increased risk of bladder cancer has been shown to correspond with this gene defect. No reports, however, have been found in the literature regarding GSTM1 gene deficiency with superficial and invasive bladder cancer. In this study, we examined the association of the GSTM1-null genotype with superficial and invasive bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the GSTM1 gene defect in Turkish patients with superficial bladder cancer (N = 61), invasive bladder cancer (N = 42), and control subjects (N = 202) who had no history of cancer. The GSTM1 null genotype was observed in 34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR: 2.246; 95% CI: 1.384-3.645, P: 0.00094). In other words, the presence of the GSTM1-null genotype significantly increased the risk of bladder cancer development. Among invasive bladder cancers, the frequency of the GSTM1-null genotype was 64.3% (OR: 0.294, 95% CI: 0.147-0.590, P: 0.0003). This was also significantly higher than control subjects, indicating that patients carrying this genotype were at increased risk for developing invasive bladder cancer. This relationship was not statistically significant in the superficial bladder cancer group (OR: 0.585, 95% CI: 0.327-1.045, P: 0.06). Our results indicate that GSTM1 gene polymorphism should be considered as an important risk modifier in the development of bladder cancer and might be used as a predictive marker for invasive bladder cancer.     

ABCB1 polymorphisms associated with osteonecrosis of the femeral head

Aims: This case-control study was conducted to investigate the relation of ATP-binding cassette subfamily B member 1 (ABCB1) C1236T and C3435T polymorphisms and non-traumatic osteonecrosis of the femeral head (ONFH). Methods: We gathered 113 ONFH patients and 116 controls in the study. The polymorphisms of ABCB1 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Odds ratio (OR) with 95% confidence interval (CI) were adopted to analyze the correlation between ABCB1 polymorphisms and ONFH. Results: In the study, we found that the frequency of C3435T TT genotype was much lower in case group, compared with that of controls (17.7% vs. 23.3%). Moreover, OR and 95% CI values indicated that C3435T TT genotype served as a protective factor for ONFH (OR=0.34, 95% CI=0.15-0.75). Meanwhile, the risk for the T allele carriers was much lower than C allele (OR=0.60, 95% CI=0.42-0.87). However, C1236T polymorphism showed no significant effects on the pathogenesis of ONFH. In the haplotype analysis, T-T haplotype appeared to be an inhibitor for ONFH (OR=0.45, 95% CI=0.23-0.87). Conclusions: Based on the results, ABCB1 polymorphisms were associated with the risk for ONFH.     

CYP2E1 RsaI/PstI polymorphisms contributed to oral cancer susceptibility: a meta-analysis

Several studies have investigated the associations between CYP2E1 RsaI/PstI polymorphisms and oral cancer risk, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. PubMed and China National Knowledge Infrastructure (CNKI) searches were carried out for relevant studies published before September 2014. Meta-analysis was performed with the Stata, version 11.0. A total of 14 case control studies, including 1,962 cases and 3,271 controls, were selected. Overall, significant association was found between the CYP2E1 RsaI/PstI polymorphisms and oral cancer risk (for c1c1 vs. c1c2, OR=0.72, 95% CI=0.56-0.91; for c1c1 vs. c2c2, OR=0.45, 95% CI=0.25-0.82), while not for the dominant model (c1c1 vs. c1c2+c2c2, OR=0.84, 95% CI=0.69-1.01). In the subgroup analysis by ethnicity, statistically significant association was found in Caucasian, East Asian and South Asian. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphisms are a risk factor for developing oral cancer.     

The role of glutathione transferases M1 and T1 in individual susceptibility to bladder cancer in a Tunisian population

BACKGROUND: Susceptibility to bladder cancer is thought to depend on interplay between genetic factors and environmental chemical carcinogens. AIM: This study seeks to determine the role of the glutathione transferases M1 and T1 null genotypes (GSTM1*0 and GSTT1*0) in individual susceptibility to bladder cancer in a Tunisian population. METHOD: Sixty-two patients with transitional cell carcinoma of the bladder cancer and 79 controls were examined with respect to the frequency of GSTM1 and GSTT1 null genotypes. RESULTS: The frequencies of the GSTT1 null in the total group of bladder cancer cases vs. controls did not differ statistically. The proportion of GSTM1 null genotype in patients was 63% compared to 45% in controls group (OR = 2.03; 95% CI 0.97-4.24; p = 0.04). A significantly higher incidence of GSTM1 deletion genotype was found in smokers with bladder cancer compared to the controls (65.38% vs. 45.5%). Smokers lacking the GSTM1 gene are at an approximately 2.2-fold higher risk of bladder cancer (OR= 2.23, 95% CI 1-5.15; p = 0.03). CONCLUSION: This study suggests that in Tunisian subjects the GSTM1 null genotype may be associated with an increased risk of bladder cancer. This association appears to depend upon smoking status.     

Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer

Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case–control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455→G), and GSTP1 (A313→G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case–controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76–2.41 and OR = 0.75; 95% CI = 0.41–1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01–3.12 and OR = 1.99; 95% CI = 1.07–3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.