Synergistic effects of metformin and curcumin on cytotoxicity of chemotherapy drugs using a gastric cancer cell line model.

Gastric cancer has a weak prognosis and its usual treatments depend on surgery and chemotherapy. These treatments suffer from some drawbacks such as high rates of local recurrence and metastasis, low survival rates, and significantly decreased life quality. Therefore, new therapeutic methods for improved gastric cancer care with minimal side effects seem necessary. Currently, combinatorial treatments for cancer are preferred and recently, metformin (Met) and curcumin (Cur) have been interesting options for this type of therapy. The aim of the present study was to investigate anticancer effects of metformin and curcumin in both single and combinatorial treatment forms on AGS gastric cancer cell line. In comparison to single treatments with each substance, the results of co-treatments with metformin and curcumin indicated synergistic inhibitory effects on cell viability, wound healing, cell migration and invasion, and primary tumor formation. To determine the selective effect of combination of "Met + Cur" on cancerous cells, very low doses of 8 anticancer drugs (cisplatin, carboplatin, oxaliplatin, epirubicin, doxorubicin, docetaxel, paclitaxel, and methotrexate) used in MTT assay were comparatively tested on AGS cancer cells and normal HDF cells for 48 and 72 hours. The results indicated that the combination of "Met + Cur" significantly increased cytotoxic effects of all anticancer drugs of AGS cells. It is while in normal HDF cells, combination of "Met + Cur" along with anticancer drugs had no effect. This can be inferred as selectively additive effect.

Association between Genetic Polymorphisms in Superoxide Dismutase Gene Family and Risk of Gastric Cancer.

To determine the association between the SOD1 (Ins/Del), SOD2 (rs2758339, rs5746136), and SOD3 (rs2536512) polymorphisms and the risk of gastric cancer the present study performed. This is a case-control study, including 159 patients with gastric cancer and 242 healthy controls. All subjects were Persian Muslims living in Shiraz (south west Iran). Frequency matching by age and gender was performed. Genomic DNA was extracted from whole blood. Genotypes of the study polymorphism were determined using polymerase chain reaction based methods. The SOD1 Ins/Del and SOD3 rs2536512 polymorphisms did not appear to have relationship with gastric cancer risk. Both SOD2 polymorphisms (rs2758339, rs5746136) showed significant association with the risk of gastric cancer, under assumption that the variant alleles act as dominant alleles. There was significant association between smoking habit and the risk of gastric cancer (OR = 2.54, 95% CI = 1.61-4.02, P < 0.001). Smoker individuals having two putative high-risk genotypes showed elevated risk of gastric cancer compared with nonsmokers without high-risk genotypes, (OR = 5.75, 95% CI = 1.59-20.6, P = 0.007). Assuming that smoking habit and the genotypes are independent risk factors, there was a significant linear trend for the numbers of risk factors and gastric cancer risk (χ2 = 22.9, P < 0.001). This study indicates that the SOD2 polymorphism (rs2758339, rs5746136) is associated with increased risk of gastric cancer, especially in smoker individuals.

Gene Expression Profile of Toll-Like Receptor/Adaptor/Interferon Regulatory Factor/Cytokine Axis During Liver Regeneration After Partial Ischemia-Reperfusion Injury.

OBJECTIVES: Toll-like receptors and downstream signal transduction pathways play pivotal roles in induction of inflammation, which is crucial for liver injury and regeneration. MATERIALS AND METHODS: Using a mouse model of partial hepatic ischemia-reperfusion injury followed by a 28-day time course for liver repair and regeneration, we assessed gene expression levels for Toll-like receptors, myeloid differentiation primary response 88, TIR-domain-containing adapter-inducing interferon-ß, nuclear factor κB, interferon regulatory factors, tumor necrosis factor-α, and interleukins 1ß and 6 at days 1, 4, 7, 14, and 28 after reperfusion in liver and blood cells by quantitative polymerase chain reaction. RESULTS: Mouse liver was gradually injured until 24 hours after reperfusion, and necrotic areas remained for 7 days. Concurrent with liver necrosis, overexpression of hepatocyte growth factor in blood cells (days 1-14), transient overexpression of cyclin D1 at day 7 in hepatic cells, and overexpression of transforming growth factor-ß1 at days 7 and 14 in blood cells were used to characterize the priming, proliferative, and termination phases of liver regeneration. Liver regeneration was associated with significant up-regulation of Toll-like receptor 4, p65, interferon regulatory factors 1, 3, 9, tumor necrosis factor-α, and interleukin 1ß at 24 hours. Liver regeneration was also associated with persistent overexpression of MyD88 (days 1-28) and with delayed TIR-domain-containing adapter-inducing interferon-ß (days 4-28) in hepatic cells. In peripheral blood cells, Toll-like receptor 2 and MyD88 were up-regulated at 24 hours and Toll-like receptor 4 (days 1-14) and interferon regulatory factor 1 (days 1-7) showed persistent overexpression concomitant with interferon regulatory factor 5 (days 7-14); interleukin 1ß (days 1-28) and interleukin 6 (day 4-28) also showed persistent expression. CONCLUSIONS: We depict for the first time a prospective view of cooperative transcriptional activation of Toll-like receptors/adaptors/interferon regulatory factors/cytokines in both liver and blood cells during different phases of liver repair after ischemia-reperfusion injury.

A new simple method for estimation of allelic frequencies using pooled samples.

Today several millions polymorphic sites in human genome are well described. Many investigators are studying the association between these polymorphisms and susceptibility to multifactorial traits. These polymorphisms are also used for studying the population's genetic structures. Here, we introduce a new simple one step method for estimating the allelic frequency of polymorphic sites in pooled samples. The method is based on measurement of the intensity of polymorphic bands on agarose gel electrophoresis. This method is very simple, rapid, inexpensive, and is more sensitive compared to the chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method.

Association between polymorphisms of Xeroderma pigmentosum complementation group C gene (XPC) and susceptibility to schizophrenia.

Previous studies revealed that polymorphisms in several DNA repair genes are associated with the risk of schizophrenia. The relationship between three polymorphisms (Ala499Val, PAT, and Lys939Gln) of the XPC (MIM: 613208) and the risk of schizophrenia is investigated. A total of 361 schizophrenia cases and 360 healthy controls were included in the study. Statistical analysis revealed that the Ala/Val genotype (OR = 0.62, P = 0.004) and the carriers of the Val allele (OR = 0.64, P = 0.006) were negatively associated with the risk of schizophrenia. The other two examined polymorphisms did not reveal significant association. The "Val - Lys" haplotype was associated with decrease risk of schizophrenia (OR = 0.71, P = 0.020). It has been showed that the haplotype "Val - Lys" had the lowest DNA damages, indicating that has higher DNA repair capacity. Here we found that this haplotype is associated with lower risk for schizophrenia.

Evaluating mRNA Expression Levels of the TLR4/IRF5 Signaling Axis During Hepatic Ischemia-Reperfusion Injuries.

OBJECTIVES: Hepatic ischemia and reperfusion during liver transplant surgery result in hepatocellular damage. Toll-like receptors, especially TLR4, have a fundamental basic role in the inflammatory phase of ischemia-reperfusion injuries. The effect of the TRIF-dependent signaling pathway downstream of TLR4 in hepatic ischemia-reperfusion injury has been well established. However, the role of TLR4-MyD88-dependent signal transduction in hepatic ischemia-reperfusion injury has not yet been clarified. The interferon regulatory factor 5 was introduced as the main regulator of the TLR4-MyD88 signaling pathway for activating proinflammatory cytokines. The present study was carried out to investigate the functional impact of the TLR4/IRF5 signaling axis in hepatic ischemia-reperfusion injury. MATERIALS AND METHODS: mRNA expression levels of TLR4, IRF5, tumor necrosis factor α, interleukin 1ß, and interleukin 6 were measured using real-time polymerase chain reaction after short (3 h) and long (168 h) reperfusion periods in a hepatic mouse model of ischemia-reperfusion injury in the presence and absence of N-acetylcysteine. Liver damage was evaluated by plasma levels of alanine aminotrans-ferase and histopathology. RESULTS: Our results show that mRNA levels of TLR4/IRF5 and its downstream cytokines were significantly elevated 3 hours after reperfusion and had drastically fallen to baseline levels 168 hours after reperfusion. Plasma levels of alanine aminotransferase showed the same pattern. Histopathologic study of the samples revealed significant hepatic cell infiltration and necrosis 168 hours after reperfusion. Pretreatment with N-acetylcysteine significantly decreased the mRNA levels of TLR4/IRF5 and its downstream cytokines 3 hours after reperfusion and subsequently improved the previously mentioned hepatic damages 168 hours after reperfusion. CONCLUSIONS: This study suggests a possible role for the TLR4/IRF5 signaling pathway in hepatic ischemia-reperfusion injury. Furthermore, it reveals that N-acetylcysteine may suppress this inflammatory axis and consequently improve hepatic injuries.

Genetic polymorphisms of superoxide dismutase-1 A251G and catalase C-262T with the risk of colorectal cancer.

Oxidative stress is significant in numerous types of disease including cancer. To protect cells and organs against reactive oxygen species (ROS), the body has evolved an antioxidant protection system that involved in the detoxification of ROS. Single nucleotide polymorphisms (SNP) of anti-oxidative enzymes may dramatically change the activity of the encoded proteins; therefore, certain alleles can be established as risk factors for some kind of multi-factorial diseases including cancer. In present study we investigate the possible association between polymorphisms of superoxide dismutase 1 (SOD1, OMIM: 147450) and catalase (CAT, OMIM: 115500) genes and the risk of colorectal cancer (CRC). The study included 204 colorectal cancer patients and 239 healthy control group matched for gender and age. Genotyping of SOD1 A251G and CAT C-262T were done by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. There was no significant association between CAT C-262T polymorphism and susceptibility to CRC (P>0.05). The carries of the G allele of SOD1 significantly showed higher prevalence in CRC patients compared with the control group (OR=1.84, 95% CI=1.13-2.98, P=0.013). We assessed the effect of combination of genotypes of the study polymorphisms on the risk of CRC. We found that the combination of AG+GG (SOD1) and CC (CAT) increases the risk of developing CRC (OR=2.38, 95% CI=1.25-4.52, P=0.008).

Effect of Sodium Arsenite on the Expression of Antioxidant Genes (SOD2 and CAT) in MCF-7 and Jurkat Cell Lines.

BACKGROUND: Sodium arsenite (NaAsO2) has potent cytotoxic activity in human cancer cells. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. The purpose of the present study was to evaluate the alteration of mRNA levels of catalase (CAT) and superoxide dismutase 2 (SOD2) in MCF-7 and Jurkat cells after exposure to NaAsO2. METHODS: Methylthiazol tetrazolium (MTT) viability assay was performed to evaluate cytotoxicity of NaAsO2 in MCF-7 and Jurkat cells. For evaluating the expression levels of the CAT and SOD2, we used two concentrations of NaAsO2 (5 and 15 µM), lower than the concentrations at which 50% of cell viability were lost. The cells were treated with co-treatment of NaAsO2 (15 µM) and N-acetyl-cysteine (NAC; 5 µM) in the media for 24 h. The control cells were maintained in sodium arsenite free growth medium. The experiments were done triplicate. Using quantitative real-time PCR, the expression levels of CAT and SOD2 were quantified. One sample student's t test was performed for comparisons of mRNA levels between treatment groups and their corresponding untreated control cells. RESULTS: CAT mRNA level decreased significantly in both cell lines following exposure to NaAsO2 (P<0.05). Expression levels of SOD2 decreased in Jurkat cells and increased in MCF-7 cells after treatment with NaAsO2 (P<0.05). CONCLUSION: After cells exposure to NaAsO2, CAT mRNA level decreased in both examined cell lines but the alterations of SOD2 mRNA level is cell specific. The NAC modulated the NaAsO2 associated alterations of CAT and SOD2 mRNA levels, therefore, the NaAsO2 might act through inducing reactive oxygen species.

Effects of extremely low frequency electromagnetic field and cisplatin on mRNA levels of some DNA repair genes.

AIMS: It has been shown that exposure to extremely-low frequency (˂300Hz) oscillating electromagnetic field (EMF) can affect gene expression. The effects of different exposure patterns of 50-Hz EMF and co-treatment of EMF plus cisplatin (CDDP) on mRNA levels of seven genes involved in DNA repair pathways (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4) were evaluated. MAIN METHODS: Two 50-Hz EMF intensities (0.25 and 0.50mT), three exposure patterns (5min field-on/5min field-off, 15min field-on/15min field-off, 30min field-on continuously) and two cell lines (MCF-7 and SH-SY5Y) were used. The mRNA levels were measured using quantitative real-time PCR. KEY FINDINGS: The examined genes had tendency to be down-regulated in MCF-7 cells treated with EMF. In the pattern of 15min field-on/15min field-off of the 0.50mT EMF, no increase in mRNA levels were observed, but the mRNA levels of GADD45A, XRCC1, XRCC4, Ku80, Ku70, and LIG4 were down-regulated. A significant elevation in IC50 of CDDP was observed when MCF-7 and SH-SY5Y cells were co-treated with CDDP+EMF in comparison with the cells treated with CDDP alone. GADD45A mRNA levels in MCF-7 and SH-SY5Y cells co-treated with CDDP+EMF were increased and at the same time the mRNA levels of XRCC4, Ku80, Ku70 and DNA-PKcs were down-regulated. SIGNIFICANCE: Present study provides evidence that co-treatment of CDDP+EMF can enhance down-regulation of the genes involved in non-homologous end-joining pathway. It might be suggested that co-treatment of CDDP+EMF could be more promising for sensitizing cancer cells to DNA double strand breaks.

Influence of A-21T and C-262T genetic polymorphisms at the promoter region of the catalase (CAT) on gene expression.

OBJECTIVE: Catalase (CAT, OMIM: 115500) is one of the major antioxidant enzymes, which plays an important role in the clearance of reactive oxygen species. Three genetic polymorphisms of A-21T (rs7943316), C-262T (rs1001179), and C-844T (rs769214) in the promoter region of the CAT have been reported. It has been suggested that these polymorphisms may alter the recognition sites of transcriptional factors, therefore it might be concluded that these polymorphisms may alter the expression levels of the gene. The aim of the present study is to evaluate the associations between these genetic variations and the CAT mRNA levels in human peripheral blood cells. METHODS: The present study consisted of 47 healthy students of Shiraz University (south-west Iran). Genotypes of the CAT polymorphisms were determined by PCR based method. The quantitative CAT mRNA expression levels were investigated using quantitative real-time PCR. RESULTS: Analysis of variance revealed significant differences between the study genotypes (For A-21T polymorphism: F = 7.45; df = 2, 44; P = 0.002; For C-262T polymorphism: F = 15.17; df = 2, 44; P < 0.001). The studied polymorphisms showed linkage disequilibrium (D' = 1.0, r 2 = 0.1813, χ 2 = 17.03, P < 0.0001). The mRNA levels of CAT in the AC/TT, TC/TC, TC/TT, and TC/TC diplotypes significantly were higher than the mRNA levels in AC/AC diplotype. There was a significant difference between the study genotypes (F = 9.24; df = 5, 41; P < 0.001). The TC/TC and TT/TT diplotypes showed about 2 and 4 folds CAT mRNA levels compared with the AC/AC diplotype. CONCLUSIONS: The present findings indicated that these polymorphisms were significantly associated with the gene expression.

Down-regulation of antioxidant genes in human SH-SY5Y cells after treatment with morphine.

AIMS: Morphine strongly induces reactive oxygen species (ROS). The deleterious actions of morphine can be countered by antioxidant system. In the present study, we investigated the expression levels of nine antioxidant genes in human SH-SY5Y cells treated with morphine. MAIN METHODS: The cells were treated with three final concentrations of morphine (1, 5, and 10 µmol) for four exposure times (1 h, 24 h, 72 h and 18 days). The mRNA levels were determined using quantitative real-time RCR. KEY FINDINGS: Based on the alterations of mRNA levels, the genes might be categorized into three different groups: In the first group, the mRNA levels of the CAT, SOD1 and GSTM3 genes were significantly down-regulated in all examined experimental conditions. In the second group, the mRNA levels of SOD2, NQO1, GSTM2 and GSTO1 were initially increased and then decreased. In the third group, the mRNA levels of NQO2 and GSTP1, were initially increased and then reached to the control levels. The number of down-regulated genes were significantly increased as a function of exposure time (χ(2)=7.52, P=0.006). We investigated the effect of morphine (10 µmol) in the absence and presence of N-acetyl-cysteine (NAC, 1 mmol). The mRNA levels revealed significant differences between cells exposed to morphine and cells co-treated with morphine plus NAC. In cases that morphine increased the level of mRNAs, morphine plus NAC, result in decreased mRNA levels and vice versa. SIGNIFICANCE: These findings suggested that there are different pathways for regulation of antioxidant genes after SH-SY5Y cells exposed to morphine and morphine might act through inducing ROS.

Association of GSTO2 (N142D), GSTT1, and GSTM1 Polymorphisms With Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Graft-versus-host disease is a major problem after bone marrow transplant. GSTM1, GSTT1, and GSTO2 are important genes that interfere with xenobiotic and drug metabolism. Polymorphisms of these genes may influence the metabolism of immunosuppressive drugs given for inhibition of graft-versus-host disease and may influence their susceptibility to diseases, which bone marrow transplant could alleviate. MATERIALS AND METHODS: We examined the polymorphisms of 2 groups: The first group was composed of 88 patients who had undergone a bone marrow transplant and 100 otherwise healthy persons; the second group was composed of 54 patients without graft-versus-host disease and 34 patients with graft-versus-host disease. We used polymerase chain reaction-restriction fragment length polymorphism method for genotyping GSTO2 and also for multiplexing polymerase chain reactions for GSTT1 and GSTM1 genotypes. RESULTS: No significant association existed between the genotypes GSTO2 (DD: P = .458, OR 0.422), GSTM1 (P = .349, OR 1.52), or GSTT1 (P = .887, OR 1.086), and the incidence of GVHD. Moreover, we saw no association between these polymorphisms and the problems that lead to bone marrow transplant (GSTO2: DD, P = .181, OR 0.465; GSTM1: P = .699, OR 0.892; GSTT1: P = .656, OR 0.845). We showed that men have more bone marrow transplants than do women (P = .019, OR 2.034). CONCLUSIONS: Our results show that these poly-morphisms may have no effect on the metabolism of drugs used to treat graft-versus-host disease and also, may play no significant role in creating the problems that lead to bone marrow transplant.

Susceptibility to Colorectal Cancer and Two Genetic Polymorphisms of XRCC4.

The X-ray complementing group 4 (XRCC4, OMIM: 194363) plays a key role in non-homologous end-joining DNA repair pathway in mammalian cells. This pathway is believed to help maintain genomic stability. In the present study, it is hypothesized that genetic polymorphisms in the NHEJ repair XRCC4 gene may be associated with an increased risk in developing colorectal cancer (CRC). We genotyped two polymorphisms of XRCC4, G-1394T (rs6869366) and intron 3 insertion/deletion (I/D; rs28360071) in 200 colorectal cancer patients as well as 256 healthy individuals, and evaluated their association with CRC. We found that in G-1394T polymorphism, neither the TG nor the GG genotypes (versus the TT genotype) were associated with the risk of developing CRC. The results of our study indicate that in comparison with the II genotype, ID and DD genotypes had no significant association with the risk of developing CRC. Subjects with TT genotype and positive family history in colorectal cancer were found to be at a much lower risk of developing CRC in comparison with the reference group (OR = 0.31, 95%CI: 0.11-0.85, P = .023). It should be noted that participants having at least one G allele (TG+GG genotypes) were at a significantly higher risk to develop the disease compared with the reference group (OR = 9.10, 95%CI: 2.00-41.3, P = 0.004). In relation to I/D polymorphism, among participants, those with positive family history, either with ID (OR = .78, 95%CI: 2.26-10.0, P < 0.001) or DD genotypes (OR = 5.73, 95%CI: 1.99-16.4, P = 0.001) had a significantly association with the disease. Among participants with a positive family history in CRC, the haplotype GD dramatically increased the risk of developing CRC (OR = 10.2, 95%CI: 2.28-46, P = 0.002). The results of this study indicate that G-1394T and I/D polymorphisms of XRCC4 among individuals with positive family history for colorectal cancer substantially increase the risk factor for developing colorectal cancers.

Effects of teicoplanin on cell number of cultured cell lines.

Teicoplanin is a glycopeptide antibiotic with a wide variation in human serum half-life. It is also a valuable alternative of vancomycin. There is however no study on its effect on cultured cells. The aim of the present study was to test the effect of teicoplanin on cultured cell lines CHO, Jurkat E6.1 and MCF-7. The cultured cells were exposed to teicoplanin at final concentrations of 0-11000 µg/ml for 24 hours. To determine cell viability, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed. At low concentrations of teicoplanin the numbers of cultured cells (due to cell proliferation) were increased in the three cell lines examined. The maximum cell proliferation rates were observed at concentrations of 1000, 400, and 200 µg/ml of teicoplanin for CHO, MCF-7 and Jurkat cell lines, respectively. Cell toxicity was observed at final concentrations over 2000, 6000, and 400 µg/ml of teicoplanin for CHO, MCF-7 and Jurkat cell lines, respectively. A dose-dependent manner of cell toxicity was observed. Our present findings indicated that teicoplanin at clinically used concentrations induced cell proliferation. It should therefore be used cautiously, particularly in children, pregnant women and patients with cancer.

The relationship between NQO1 C609T and CAT C-262Tgenetic polymorphisms and the risk of age-related cataracts.

Cataract is multi-factorial eye disease identified by the disturbance of the transparent ocular lens. There is significant evidence suggesting oxidative damage as a major cause of initiation and progression of numerous diseases including cataracts. NAD(P)H:quinone oxidoreductase 1 (NQO1; OMIM: 125860) and catalase (CAT, OMIM: 115500) are antioxidant enzymes that prevent cells from oxidative stress. The aim of the present study was to investigate the association between NQO1 C609T (Pro189Ser, rs1800566) and CAT promoter C-262T (rs1001179) genetic polymorphisms and the susceptibility to cataracts. A case-control study including 190 cataracts cases and 190 healthy subjects was carried out. Genotype distributions of NQO1 and CAT polymorphisms were examined using polymerase chain reactions and a restriction fragment length polymorphism (PCR-RFLP) approach to investigate the possible role of these polymorphisms as risk factors in the development of cataracts. Variant CT heterozygous and TT genotypes of the NQO1 C609T polymorphism were found to be associated with an increased risk of cataracts (CT vs CC, OR=1.61, 95%CI: 1.02-2.52, P=0.038), (CT/TT vs CC, OR=1.56, 95%CI: 1.02-2.4, P=0.040). In addition, compared to indoor work places and the CC genotype of NQO1, outdoor work places and CT/TT genotypes of NQO1 were found to increase the risk of age-related cataracts (OR=2.75, 95%CI: 1.20-6.33, P=0.017). The analysis did not reveal, however, any statistically significant (P>0.05) difference between CAT C-262T polymorphism and the risk of cataracts.

Association between VNTR polymorphism in promoter region of prodynorphin (PDYN) gene and heroin dependence.

Within the core promoter region of prodynorphin (PDYN), a 68-bp sequence was found to occur as a polymorphism element, either singular or as tandemly repeated two, three or four times. We report the sequence of a novel allele (5-repeats). Our study revealed the existence of an ancestral nucleotide (A) at 29th position of the VNTR in human. In total, 442 heroin addicts and 799 controls were included in this study. The present findings revealed a male-limited association between VNTR polymorphism and heroin dependence risk.

Association between polymorphisms at promoters of XRCC5 and XRCC6 genes and risk of breast cancer.

Variation in DNA repair genes is one of the mechanisms that may lead to variation in DNA repair capacity. Ku, a heterodimeric DNA-binding complex, is directly involved in repair of DNA double-strand breaks. Ku consists of two subunits, Ku70 and Ku80, which are encoded by the XRCC6 and XRCC5 genes, respectively. In the present study, we investigated whether common genetic variant in variable number of tandem repeats (VNTR) XRCC5 and T-991C XRCC6 was associated with an altered risk of breast cancer. The present study included 407 females with breast cancer and 395 age frequency-matched controls which were randomly selected from the healthy female blood donors. The XRCC5 and XRCC6 polymorphisms were determined using PCR-based methods. For XRCC5 polymorphism, in comparison with the 1R/1R genotype, the 0R/0R genotype increased breast cancer risk (OR 9.55, 95%CI 1.19-76.64, P = 0.034). The 1R/3R genotype compared with 1R/1R genotype decreased the risk of breast cancer (Fisher's exact test P = 0.015). There was no association between T-991C polymorphism of XRCC6 and breast cancer risk. Mean of age at diagnosis of breast cancer for 0, 1, 2, 3, and >4 repeat in XRCC5 were 39.2, 41.9, 44.3, 45.8, and 47.3 years, respectively. The Kaplan-Meier survival analysis revealed that the number of repeat was associated with age at diagnosis of breast cancer (log rank statistic = 13.90, df = 4, P = 0.008). The findings of the present study revealed that either breast cancer risk or age at diagnosis of breast cancer was associated with the VNTR polymorphism at promoter region of XRCC5.

Association of CAT C-262T and SOD1 A251G single nucleotide polymorphisms susceptible to gastric cancer.

Oxidative stress is known to be one of the major factors involved in the development and progression of cancer. Oxidative stress can occur due to an imbalance between concentrations of reactive oxygen species and antioxidant capacities. Catalase (CAT; OMIM 115500) and superoxide dismutase 1 (SOD1; OMIM 147450) play important roles in the primary defense against oxidative stress. In the present study, we investigated possible associations between polymorphisms of CAT C-262T (rs1001179) and SOD1 A251G (rs2070424) with susceptibility to gastric cancer. This case-control study included 160 gastric cancer patients and 241 age and gender frequency-matched healthy controls. Genotyping was done using PCR-RFLP based method. There were no significant differences in T allele frequencies in patients as compared to the controls in the CAT C-262T polymorphism (OR=0.80, 95% CI: 0.52- 1.23, P=0.304). Subjects with AG (OR=0.47, 95% CI: 0.24-0.91, P=0.026) or AG+GG (OR=0.45, 95% CI: 0.23-0.88, P=0.021) genotypes of the rs2070424 polymorphism were at lower risks of developing gastric cancer in comparison with the AA genotype. Our findings showed that there was no significant association between CAT C-262T polymorphism and gastric cancer susceptibility. However, we found that the G allele of the SOD1 A251G polymorphism has protective effects against the risk of gastric cancer.