Genetic polymorphism of p53, but not GSTP1, is association with susceptibility to esophageal cancer risk - A Meta-Analysis

A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 Arg72Pro was associated with an increased risk of esophageal cancer ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.20, 95%CI=1.06-1.36) without any between-study heterogeneity.In the stratified analysis by ethnicity, we found that the increased esophageal cancer risk associated with p53 Arg72Pro polymorphism was more evident in Asian group ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.35, 95%CI=1.14-1.60, P=0.09 for heterogeneity test), although we still failed to find any significant association between GSTP1 Ile105Val polymorphism and esophageal cancer risk in different ethnicity. These results suggest that p53 Arg72Pro polymorphism, but not GSTP1 Ile105Val, may contribute to esophageal cancer development, especially in Asian. Additional well-designed large studies were required for the validation of this association.     

Association of GSTP1 and XRCC1 gene polymorphisms with clinical outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy

We investigated the association between the clinical outcome and GSTP1 and XRCC1 gene polymorphisms in advanced NSCLC patients with cisplatin-based chemotherapy. We prospectively recruited 325 NSCLC patients between January 2010 and January 2014. Genotypes of GSTP1 A313G, XRCC1 Arg194Trp, Arg280His and Arg399Gln were conducted using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. AG and GG genotypes of GSTP1 A313G were correlated with a higher CR + PR when compared with AA genotype. Furthermore, GA and AA genotypes of XRCC1 Arg399Gln were associated with more CR + PR when compared with GG genotype. In the Cox proportional hazards model, GG genotype of GSTP1 A313G was significantly correlated with a longer median survival time when compared with AA genotype, and it is associated with a heavy decreased risk of death from NSCLC. Moreover, GA and AA genotypes of XRCC1 Arg399Gln had a significantly longer median survival time, and GA and AA genotypes were significantly associated with a moderate reduced risk of death from NSCLC. GSTP1 A313G and XRCC1 Arg399Gln gene polymorphisms might influence the response to cisplatin-based chemotherapy and affect the clinical outcome of advanced NSCLC.     

Polymorphisms of Glutathione S-Transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi 1 (GSTP1) Genes and Epithelial Ovarian Cancer Risk

Background: Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development. Objectives: We tested in this study whether the GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms alter the risk of EOC. Materials and methods: Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ² or Fisher’s exact test. Results: The frequencies of GSTP1 Ile/Ile (57.6% versus 45.5%, P = 0.03), GSTM1 null plus GSTP1 Ile/Ile (43.5% versus 25.8%; P = 0.03) and GSTM1 null plus GSTT1 null plus GSTP1 Ile/Ile (30.3% versus 7.7%; P = 0.007) genotypes were higher in patients than in controls. Individuals with the respective genotypes had a 1.80 (95% CI: 1.06–3.06), 2.38 (95% CI: 1.08–5.24) and 11.28 (95%CI: 1.95–65.30)-fold increased risks of EOC than those with the remaining genotypes. Conclusions: Our data present preliminary evidence that GSTM1, GSTT1 and GSTP1 polymorphisms, particularly in combination, constitute important inherited EOC determinants in individuals from Southeastern Brazil.     

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.     

Association of GSTs polymorphisms with risk of gestational diabetes mellitus

We conducted a case-control study to investigate the association between GSTM1, GSTT1 and GSTP1 IIe105Val polymorphisms and development of gestational diabetes mellitus in a Chinese population. A total of 320 patients with gestational diabetes mellitus and 358 pregnancy subjects were consecutively collected between January 2013 and December 2014. Genotyping for detection of GSTM1, GSTT1 and GSTP1 IIe105Val was conducted by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphisms) method. By Fisher’s exact test, we found that the genotype distributions of GSTP1 IIe105Val were in line with the Hardy-Weinberg equilibrium in control subjects (P=0.57). By Chi-square test, we found significant differences in the genotype distributions of GSTM1 (χ²=11.49, P=0.001) and GSTT1 (χ²=18.50, P<0.001). Using unconditional logistic analysis, individuals carrying the null genotypes of GSTM1 and GSTT1 were associated with an increased risk of gestational diabetes mellitus when compared with the present genotype, and the adjusted Ors (95% CI) were 1.71 (1.24-2.36) and 2.00 (1.44-2.79), respectively. However, the GSTP1 IIe105Val polymorphism was not associated with an elevated risk of gestational diabetes mellitus. In conclusion, we suggest that the GSTM1 null genotype and GSTT1 null genotype are correlated with an increased risk of gestational diabetes mellitus in a Chinese population.     

Assoication of XRCC1 gene polymorphisms with risk of non-small cell lung cancer

DNA repair genes is a key factor for cancer susceptibility, and we conducted a case-control study to investigate the association of XRCC1 codons 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln) with risk of NSCLC. 210 NSCLC patients and 210 health control subjects were randomly selected from Huaihe Hospital between January 2012 and June 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to assess the genotyping of XRCC1 Arg194Trp, Arg280His and Arg399Gln. By multivariate logistic regression analysis, we found individuals carrying with Trp/Trp and Arg/Trp + Trp/Trp genotypes were associated with a significantly increased risk of NSCLC compared with Arg/Arg genotype, and the OR (95% CI) were 3.15 (1.32-8.09) and 1.52 (1.02-2.28), respectively. The potential association of Arg/Trp+ Trp/Trp genotype of XRCC1 Arg194Trp with the risk of NSCLC is more evidence in smokers, and the OR (95% CI) was 1.78 (1.01-3.24). In conclusion, we found that XRCC1 Arg194Trp polymorphism may be associated with NSCLC risk, especially in smokers.     

Association of GSTs gene polymorphisms with treatment outcome of advanced non-small cell lung cancer patients with cisplatin-based chemotherapy

We evaluated the association of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms with the clinical response to chemotherapy and treatment outcome of NSCLC. Between October 2009 and October 2012, a total of 282 patients with advanced NSCLC were enrolled into our study, and they were followed up until October 2014. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val were performed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By logistic regression analysis, our study found that the Val/Val genotype of GSTP1 IIe105Val was associated with more CR+PR response to chemotherapy when compared with the IIe/IIe genotype, and the OR (95% CI) was 2.18 (1.16-4.12). By multivariate Cox proportional hazards regression analysis, we found the Val/Val genotype of GSTP1 was correlated with lower risk of death in advanced NSCLC (HR, 0.48; 95% CI, 0.25-0.93). However, no association was found between GSTT1 and GSTM1 polymorphisms and response to chemotherapy and overall survival of advanced NSCLC. Moreover, the IIe/Val + Val/Val genotypes of GSTP1 were associated with lower risk of death in never smokers, and the adjusted HR (95% CI) was 0.34 (0.12-0.93). In conclusion, we found that the GSTP1 polymorphism was correlated with better response to chemotherapy and lower risk of death in advanced NSCLC patients.     

Association between polymorphisms in the XRCC1 and GST genes, and CpG island methylation status in colonic mucosa in ulcerative colitis

CpG island hypermethylation (CIHM) is frequently observed in the colonic mucosa in ulcerative colitis (UC) and is deeply involved in UC-associated colorectal carcinogenesis. We evaluated the influence of common polymorphisms related to DNA repair or xenobiotic pathway (XRCC1, GSTP1, GSTT1, and GSTM1) on the individual susceptibility to CIHM status in the non-neoplastic rectal mucosa in UC patients. XRCC1 Arg399Gln and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 84 UC patients without neoplastic lesions, in relation to CIHM in the rectal mucosa of three candidate CpG loci (p14, p16, and CDH1) assessed by methylation-specific polymerase chain reaction. XRCC1 codon 399 Arg/Gln genotype (odds ratio (OR) = 0.31, 95%CI = 0.12–0.81, p = 0.017) and 399 Gln carrier (GlnGln+Arg/Gln: OR = 0.30, 95%CI = 0.12–0.76, p = 0.01) were significantly associated with reduced susceptibility to CIHM of the CDH1 promoter. GSTP1 Val carrier (Ile Val+Val/Val) also held a significantly lower susceptibility to CIHM of the p16 promoter (OR = 0.26, 95%CI = 0.08–0.86, p = 0.028). In contrast, GSTT1 present genotype (OR = 3.16, 95%CI = 1.27–7.89, p = 0.01) was significantly associated with increased susceptibility to CIHM of the same gene. XRCC1 codon 399 Gln/Gln genotype was significantly associated with lower mean number of CIHM when compared to the Arg/Arg genotype (1.53 ± 1.01 vs. 0.63 ± 1.06, p = 0.024). In addition, the GSTP1 Ile/Val carrier (Ile/Val+Val/Val) was also significantly associated with lower mean number of CIHM (1.43 ± 1.03 vs. 0.84 ± 1.07, p = 0.03). XRCC1 Arg399Gln and GSTP1 Ile104Val polymorphisms may influence the CIHM status in the rectal mucosa of UC patients and may be substantially involved in UC-associated carcinogenesis.     

Polymorphisms of the genes encoding the GSTM1, GSTT1 and GSTP1 in Korean women: no association with endometriosis

Endometriosis, one of the most common gynaecologic disorders, shows significantly elevated prevalence in industrial areas and there is also a possible genetic predisposition. Glutathione-S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing carcinogens and mutagens that are present in human environments. An association between the incidence of endometriosis and the GST genotypes of patients has been suggested. The objective of the present study was to investigate whether the polymorphisms of GSTM1, GSTT1 and GSTP1 are related to endometriosis. Blood samples were available from 259 controls and 194 patients with advanced endometriosis diagnosed by both pathology and laparoscopic findings. The proportion of the GSTM1, GSTT1 and GSTP1 genotypes of the control group were comparable to other populations. There was no significant evidence that the distribution of the GSTM1 and GSTT1 genotype differed between the patients and the controls, with an allelic odds ratio (OR)=1.074 [95% confidence interval (CI)=0.737-1.564] and 1.239 (95% CI = 0.853-1.799), respectively. Also, there was no significant difference in the proportion of GSTP1 genotypes between the women with endometriosis and the control group with the OR = 0.823 (95% CI = 0.536-1.264). The higher risk alleles were contended as GSTM1, GSTT1 null mutation and GSTP1 Ile105Ile polymorphism. There was no significant increase in the risk of endometriosis as the number of higher risk alleles of the GST family increased. In conclusion, our findings suggest that the GSTM1, GSTT1 and GSTP1 genetic polymorphisms are not associated with the development of endometriosis in Korean women.     

Effect of EME1 exon variant Ile350Thr on risk and early onset of breast cancer in southern Chinese women

Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the recognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME1 (i.e.,Ile350Thr: rs12450550T > C and Glu69Asp: rs3760413T > G) and breast cancer risk. We found that compared to the common Ile/Ile genotype, the Thr variant genotypes (Thr/Ile + Thr/Thr) conferred a 1.47-fold increased risk of breast cancer (OR=1.47, 95% CI=1.13-1.92). The variant Ile350Thr was also associated with early onset of breast cancer (r = -0.116, P = 0.002). The mean age of onset was 44.4 years for Thr/Thr genotype carriers and 46.5 years for Thr/Ile genotype carriers, which was significantly lower than that (49.4 years) for Ile/Ile genotype carriers (P = 0.006). Moreover, no significant association was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.     

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.     

Polymorphism of XRCC1 predicts overall survival of gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population

Pharmacogenetic advances in cancer chemotherapy have the potential to predict clinical benefit to particular regimens. Platinum agents have shown to be effective in the treatment of gastric cancer. We assessed whether single nucleotide polymorphisms (SNPs) in xeroderma pigmentosum group D (XPD), X-ray repair cross complementing group 1 (XRCC1) and glutathione S-transferase P1 (GSTP1) predicted overall survival in gastric cancer patients receiving oxaliplatin-based chemotherapy in Chinese population. SNPs of XPD-751, XRCC1-399 and GSTP1-105 in 62 gastric cancer patients were evaluated using the TaqMan 5' nuclease assay. Genotypes were correlated to survival. The median overall survival time was 322 days (range: 56-2058 days). The median survival times for patients with Arg/Arg or Arg/Gln genotypes of XRCC1 gene were significantly longer than others (P=0.03). For 58 patients with ECOG PS (Eastern Cooperative Oncology Group performance status)相似文献   

Association between the c.910A>G genetic variant of the XRCC1 gene and susceptibility to esophageal cancer in the Chinese Han population

Esophageal cancer (EC) is a common malignancy worldwide. The X-ray repair cross-complementing 1 gene (XRCC1) is one of the most important candidate genes for influencing susceptibility to EC. This study aimed to investigate the effect of XRCC1 genetic variants on susceptibility to EC. A total of 383 EC patients (males: 239, females: 144, mean age: 56.62) and 387 cancer-free controls (males: 251, females: 136, mean age: 58.23) were enrolled in this study. The c.910A>G genetic variant of the XRCC1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The allele and genotype frequencies indicated statistical differences between EC patients and cancer-free controls. The c.910A>G genetic variant was statistically associated with increased susceptibility to EC [GG vs AA: odds ratio (OR)=1.79, 95% confidence interval (CI)=1.12-2.86, P=0.014; GG vs AG/AA: OR=1.76, 95%CI=1.13-2.75, P=0.013; G vs A: OR=1.25, 95%CI=1.01-1.55, P=0.041]. The allele G and genotype GG could contribute to the increased susceptibility to EC. Our findings suggest that the c.910A>G genetic variant is associated with susceptibility to EC in the Chinese Han population, and might be used as a molecular marker for detecting susceptibility to EC.     

Gene-gene interactions among CX3CL1, LEPR and IL-6 related to coronary artery disease in Chinese Han population

Objective: The purpose of this study was to investigate the impact of the interactions among CX3CL1 (rs170364 and rs614230), LEPR (rs6700896), and IL-6 (rs2066992) polymorphisms on the risk of coronary artery disease (CAD) in Chinese Han population. Methods: 120 CAD patients and 109 healthy controls were enrolled in the study. Polymerase chain reaction (PCR) and direct sequencing methods were used to analyze the genotypes of CX3CL1, LEPR, and IL-6 polymorphisms. Multifactor dimensionality reduction (MDR) software was utilized to analyze gene-gene interactions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used for evaluating the association between gene polymorphisms or gene-gene interactions and CAD risk. Results: In the study, TT genotype of rs170364 in CX3CL1 might decrease the CAD risk (OR=0.39, 95% CI=0.16-0.98). No significant correlation was found between T allele of rs170364 and CAD risk (P>0.05). CC genotype and C allele in rs614230 (CX3CL1) were significantly related with decreased risk of CAD (OR=0.38, 95% CI=0.17-0.86; OR=0.66, 95% CI=0.45-0.97). For IL-6 rs2066992 polymorphism. GG genotype could increase the risk of CAD (OR=2.32, 95% CI=1.04-5.17). Whereas, no significant correlation was observed between LEPR rs6700896 and CAD susceptibility. MDR analysis showed that CX3CL1, LEPR and IL-6 genes might jointly promote the occurrence of CAD. Conclusions: The interactions of CX3CL1, LEPR and IL-6 genes might increase the risk of CAD.     

Association between COX-2 polymorphisms and non-small cell lung cancer susceptibility

Aim: To explore the association between COX-2 polymorphisms and non-small cell lung cancer (NSCLC) susceptibility. Methods: We collected fasting peripheral venous blood from 60 cases with NSCLC and 62 healthy controls through physical examinations, and applied PCR-RFLP to analyze COX-2 polymorphisms of two groups. Results: With respect to detecting COX-2 rs689466 and rs5275 polymorphisms, the distribution frequency of mutant genotype AA of COX-2 rs689466 in case group was higher than that in control group, which possessed significant difference between two groups (P < 0.05). Carriers with AA genotype were 4.05 times at risk of NSCLC than those with GG genotype (P = 0.04, OR=4.05, 95% CI = 1.14-14.43). The distribution of mutant genotype CC of COX-2 rs5275 was different between two groups, and carriers with genotype CC were at 5.70 times higher risk of NSCLC than those with genotype TT. After corrected by sex, gender, smoking and drinking factors, AA genotype of COX-2 rs689466 and CC genotype of COX-2 rs5275 still contributed to increased risk of NSCLC (OR=4.22, 95% CI=1.10-16.17, OR=6.95, 95% CI=1.27-38.11). After analyzed of linkage disequilibrium (LD) and haplotypes of alleles in two SNPs, the distribution frequency of A-C haplotype in case group was higher than that in control group, with significant difference between two groups (P < 0.05). After corrected by sex, gender, smoking and drinking factors, statistical difference was still found in the total distribution of A-C haplotype between two groups (P = 0.03, OR=6.11, 95% CI=1.16-32.2). Conclusions: COX-2 rs689466 and rs5275 polymorphisms may be related to NSCLC susceptibility. And A-C haplotype might be a susceptibility haplotype for NSCLC.     

Genetic Polymorphism of GSTP1: Prediction of Clinical Outcome to Oxaliplatin/5-FU-based Chemotherapy in Advanced Gastric Cancer

The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile¹⁰⁵Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile¹⁰⁵Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were ¹⁰⁵Ile/¹⁰⁵Ile 52%, ¹⁰⁵Ile/¹⁰⁵Val 41% and ¹⁰⁵Val/¹⁰⁵Val 7%. For patients with ¹⁰⁵Ile/¹⁰⁵Ile and those with at least one ¹⁰⁵Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two ¹⁰⁵Ile alleles (P=0.005). In conclusion, patients with at least one ¹⁰⁵Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.     

Haplotype analysis of XRCC1 (at codons 194 and 399) and breast cancer risk, a case–control study

DNA in most cells is regularly damaged by endogenous and exogenous mutagens. Among DNA repair systems, the base excision repair pathway is responsible for the repair of oxidative DNA damage and single-strand breaks. The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. Several polymorphisms in the XRCC1 gene have been described, including Arg194Trp (db SNP rs. 1799782). Since it has been suggested that the XRCC1 codon 194 polymorphism might be associated with significant alterations in the DNA repair capacity, the present study was undertaken. Blood samples from 186 females with breast cancer and 187 age- and sex-matched healthy individuals were collected. The genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism method. Allele frequency of 194Trp was low in both cancer patients and controls (0.0968 and 0.0802, respectively) and exhibited a similar distribution within both groups (odd ratio = 1.22, 95% confidence interval: 0.74–2.04, P = 0.426). The association between Arg194Trp polymorphism and breast cancer risk was not significant neither in Trp/Trp (P = 1.0) nor Arg/Trp (P = 0.273) genotypes compared with the Arg/Arg genotype. The close physical proximity of the polymorphisms at codons 194 and 399 of XRCC1 place them in linkage disequilibrium (patients: D′ = 0.8386, P < 0.001; controls: D′ = 1.0, P < 0.001). However, no significant difference between frequencies of the four types of haplotypes among cases and controls (P > 0.05) was noted.     

Genetic variability of ERCC1 genes in NER pathway influences the treatment outcome of gastric cancer

We conducted a prospective study to analyze whether six SNPs in ERCC1 gene could serve as potential biomarkers for prognosis of gastric cancer. Between January 2010 and December 2012, 270 patients with pathologically proven gastric cancer and receiving platinum-based chemotherapy were recruited in our study. Genotyping of the ERCC1 rs11615, rs2298881, rs3212955, rs3212961, rs3212986 and rs735482 were carried out using the Sequenom MassARRAY platform. By logistic regression analysis, patients carrying the GT and TT genotypes of rs3212986 showed a significantly poorer response to chemotherapy than did those carrying the GG genotype, and the ORs (95% CI) were 0.47 (0.25-0.88) and 0.18 (0.08-0.41), respectively. By Cox proportional hazards models, the GT and TT genotypes of rs3212986 were correlated with increased risk of death when compared with the GG genotype, and the adjusted HRs (95% CIs) were 1.79 (1.01-3.16) and 2.57 (1.18-5.62), respectively. However, we did not find significant association between ERCC1 rs11615, rs2298881, rs3212955, rs3212961 and rs735482 and response to chemotherapy and overall survival in patients with gastric cancer. In conclusion, the results of the present retrospective study indicate that there is a significant difference in biological behavior between ERCC1 rs3212986 gene polymorphism and treatment outcome of gastric 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.     

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.