Table 1 Proteins PKC inhibitor differentially expressed in ovariectomized rat livers after isoflavone intake and exercise

using MALDI-TOF MS/MS Spot number Accession number Official symbol Protein identification Theoretical MW(kDa)/pI Measured MW(kDa)/pI Score a Coverage 8203 NP_058797 PPIA Peptidyl-prolyl cis-trans isomerase A 18.1/8.34 17.5/9.0 86 71 9401 P81178 ALDH2 Aldehyde dehydrogenase, mitochondrial 54.8/5.83 46.4/6.6 298 12 3607 NP_001101972 BUCS1 Butyryl Coenzyme A synthetase 1 27.8/5.57 50.1/5.1 39 13 5701 BAA08207 PSME2 Proteasome activator rPA28 subunit beta 27.1/5.52 30.1/5.3 75 13 8002 AAB19918 AKR1C3 3 alpha-hydroxysteroid dehydrogenase 37.6/7.03 36.1/7.4 121 9 9801 AAA41769 OTC Ornithine carbamoyltransferase 39.9/9.1 52.1/7.8 220 14 5503 NP_001102492 INMT Indolethylamine buy AZD6738 N-methyltransferase 30/5.7 29.3/5.4 99 12 6601 NP_036925 GAMT Guanidinoacetate N-methyltransferase 26.7/5.69 28.2/5.8 48 16 a Score is −10xlog(P), where P is the probability that the observed match is a random event, based on the NCBInr database using the MASCOT searching program as MS/MS data. Comparison of hepatic protein expressions between sham-operated and ovariectomized rats Hepatic protein profiles for each SHAM and OVX group are shown in Figure  1A and B. Spot number 5503 (INMT)

was detected in the SHAM but not in any of the other ovariectomized groups (Figure  2). On the other hand, when compared to the SHAM, ovariectomized rats demonstrated an increase in protein levels, which were spot

numbers 8203 (PPIA, 2.83 fold up), 3607 (BUCS1, 5.86 fold learn more up), 5701 (PSME2, 3.93 fold up), 8002 (AKR1C3, 3.61 fold up), and 6601 (GAMT, 2.57 fold up). Two protein spots were down-regulated in ovariectomized rats when compared to the SHAM group, which include spot numbers 9401 (ALDH2, 1.54 fold down) and 9801 (OTC, 5.26 fold down). Effects of isoflavone supplementation on the levels of hepatic protein expression in ovariectomized rats We also determined if isoflavone supplementation could affect protein expression patterns in ovariectomized rats. The expression of hepatic proteins in ovariectomized rats on an isoflavone-supplemented diet (ISO) was compared with that of the OVX group (Figure  1B and C). Isoflavone-supplementation resulted in the down-regulation of spot number 3607 (BUCS1, a 1.82 fold down) and the up-regulation of spot numbers 8203 see more (PPIA, 1.61 fold up), 8002 (AKR1C3, a 1.57 fold up), and 9801 (OTC, 2.95 fold up) compared to the rats without isoflavone supplementation (Figure  2). Spot numbers 9401 (ALDH2), 5701 (PSME2), 6601 (GAMT), and 5503 (INMT) did not change after isoflavone supplementation (Figure  2). Effects of exercise on the levels of hepatic protein expressions in ovariectomized rats The influence of physical exercise was also examined in ovariectomized rats (Figure  1B and D). The animals that underwent regular exercise (EXE) demonstrated an up-regulation of spot numbers 5701 (PSME2, 2.

Respiration 72(4):431–446CrossRef Torres Costa J, Sá R, Cardoso MJ, Silva R, Ferreira J, Ribeiro C, Miranda M, Plácido JL, Nienhaus (2009) Tuberculosis screening in Portuguese healthcare workers using the tuberculin skin test and the Interferon-γ release assay. Eur Resp J 34:1423–1428CrossRef van Zyl-Smit R, check details Pai M, Peprah K, Meldau R, Meldau R, Kieck J, Juritz J, Badri M, Zumla A, Sechi LA, Bateman ED, Dheda K (2009) Within-subject variability and boosting of T-cell

Interferon-γ responses after tuberculin skin testing. Am J Respir Crit Care Med 180:49–58CrossRef Yoshiyama T, Harada N, Higuchi K, Nakajima Y, Ogata H (2009) Estimation of incidence of tuberculosis infection in health-care workers using repeated interferon-gamma

Tideglusib mw assays. Epidemiol Infect 1–8 Yoshiyama T, Harada N, Higuchi K, Sekiya Y, Uchimura K (2010) Use of the QuantiFERON-TB gold test for screening tuberculosis contacts and predicting active disease. Int J Tuberc Lung Dis 14(7):819–827″
“Introduction An ad hoc working group at the International Agency for Research on Cancer (IARC) considered dry-cleaning of textiles to entail exposures that are possibly carcinogenic to humans (Group 2B; IARC 1995a). Among these exposures, perchloroethylene (PER; also recognised as tetrachloroethylene) has been of special interest, and the substance has been upgraded from unclassifiable with regard to carcinogenic risk to humans (Group 3; IARC 1982) through possibly carcinogenic to humans (Group 2B; IARC 1987) to probably carcinogenic to humans (Group 2A; IARC 1995b). In their most recent evaluation, the IARC found consistently positive associations in studies of PER-exposed cohorts for cancer of the oesophagus, cervix and non-Hodgkin’s lymphoma (IARC 1995b). In a similar analysis, the US National PIK3C2G Toxicology Program (NTP) also found PER “reasonably anticipated to be a human carcinogen” (NTP 2005). Other scientific bodies have,

however, adhered to more conservative risk estimates pertaining to PER. The American Conference of Governmental Industrial Hygienists (ACGIH) for instance has labelled PER an animal carcinogen of unknown human relevance (Group A3; ACGIH 2003), and an equally cautious position has been adopted by the Deutsche Forschungsgemeinschaft (DFG) (Group 3B; “a cause for concern but lack of data”; DFG 2007). In a recent critical review, Mundt et al. (2003) ARRY-438162 mouse specifically noted the ubiquitous lack of valid exposure estimates in the epidemiological literature on PER and cancer, and they concluded that there was no epidemiological support for linking PER to cancer of any specific site. A joint Dutch-Swedish literature review found the epidemiology on PER carcinogenicity to humans inconclusive (de Raat 2003).

Eukaryot Cell 2008, 7:177–186.PubMedCrossRef 5. Cyert MS: Genetic analysis of calmodulin and its targets in Saccharomyces cerevisiae . Annu Rev Genet 2001, 35:647–672.PubMedCrossRef 6. Cruz MC, Fox DS, Heitman J: Calcineurin is required for hyphal elongation SB431542 mouse during mating and haploid fruiting in Cryptococcus neoformans . EMBO J 2001,

20:1020–1032.PubMedCrossRef 7. Kontonyannis DP, Lewis RE, Osherov N, Albert ND, May GS: Combination of caspofungin with inhibitors of the calcineurin pathway attenuates growth in vitro in Aspergillus species. J Antimicrob Chemother 2003, 51:313–316.CrossRef 8. Steinbach WJ, Singh N, Miller JL, Benjamin DK Jr, Schell WA, Heitman J, Perfect JR: In vitro interactions between antifungals and immunosuppressants

against Aspergillus fumigatus isolates from transplant and nontransplant patients. Antimicrob Agents Chemother 2004, 48:4922–4925.PubMedCrossRef 9. da Silva Ferreira ME, Heinekamp T, Härt A, Brakhage AA, Semighini CP, Harris SD, SB202190 mw Savoldi M, de Gouvêa PF, de Souza Goldman MH, Goldman GH: Functional characterization of the Aspergillus fumigatus calcineurin. Fungal Genet Biol 2007, 44:219–230.PubMedCrossRef 10. Odom A, Muir S, Lim E, Toffaletti DL, Perfect J, Heitman J: Calcineurin is required for virulence of Cryptococcus neoformans . EMBO J 1997, 16:2576–2589.PubMedCrossRef 11. Cruz MC, Sia RA, Olson M, Cox GM, Heitman J: Comparison of the roles of calcineurin in physiology and virulence in serotype D and serotype A strains of Cryptococcus neoformans . Infect Immun 2000, 68:982–985.PubMedCrossRef 12. Cruz MC, Goldstein AL, Blankenship JR, Del Poeta M, Davis D, Cardenas ME, Perfect JR, McCusker Go6983 cell line JH, Heitman J: Calcineurin is essential for survival during membrane stress in Candida albicans . EMBO J 2002, 21:546–559.PubMedCrossRef 13. Fox DS, Cruz MC, Sia RA, Ke H, Cox GM, Cardenas ME, Heitman J: Calcineurin regulatory subunit is essential for virulence and mediates interactions with FKBP12-FK506 in Cryptococcus neoformans of . Mol Microbiol 2001, 39:835–849.PubMedCrossRef 14. Sanglard

D, Ischer F, Marchetti O, Entenza J, Bille J: Calcineurin A of Candida albicans : involvement in antifungal tolerance cell morphogenesis and virulence. Mol Microbiol 2003, 48:959–976.PubMedCrossRef 15. Blankenship JR, Wormley FL, Boyce MK, Schell WA, Filler SG, Perfect JR, Heitman J: Calcineurin is essential for Candida albicans survival in serum and virulence. Eukaryot Cell 2003, 2:422–430.PubMedCrossRef 16. Soriani FM, Malavazi I, da Silva Ferreira ME, Savoldi M, Von Zeska Kress MR, de Souza Goldman MH, Loss O, Bignell E, Goldman GH: Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA. Mol Microbiol 2008, 67:1274–1291.PubMedCrossRef 17. Stathopoulos-Gerontides A, Guo JJ, Cyert MS: Yeast calcineurin regulates nuclear localization of the Crz1p transcription factor through dephosphorylation. Genes Dev 1999, 13:798–803.PubMedCrossRef 18.

Two major abiotic factors affect alpine BSC algae in particular. The first is the periods of dehydration, which slow metabolic processes. Dehydration is followed by desiccation, leading to a total cessation of metabolic processes. The second prominent abiotic factor is exposure to UVR. In the Alps, water availability frequently fluctuates, from fluid droplets after rain or snow, to extended periods of dryness or freezing. Water availability, which PD0332991 supplier includes precipitation, condensation and water vapor,

is therefore the key ecological prerequisite for long-term survival of aeroterrestrial algae, because only fully hydrated and ultrastructurally intact cells are physiologically functional (for summary see Holzinger and Karsten 2013). Comparisons with, e.g., Antarctic wetlands could be drawn, where low subzero temperatures lead to annual winter freezing. These extreme cold periods caused little harm to cyanobacteria, but were fatal to 50 % of the algal population (Šabacká and Elster 2006). The Alps are among the regions with the highest UVR levels recorded for Europe. Solar Tariquidar radiation entering the Earth’s atmosphere exhibits a typical spectrum characterized by UVR (190–400 nm), photosynthetically active radiation (PAR: 400–700 nm) and infrared radiation (IR: >700). UVR is differentiated

according to the CIE check details definition into three wavebands—UV-C: 190–280 nm, UV-B: 280–315 nm, and UV-A: 315–400 nm. Due to the absorption features of stratospheric ozone, the intensity of radiation in the UV-B range is globally increasing, because of the destruction of the stratospheric ozone. Besides clouds, atmospheric particles and snow-covered surfaces, changes in day length, season, latitude and altitude produce wide variability in the radiation conditions of terrestrial ecosystems. Particularly, the altitude effect is very well documented for the European Alps Molecular motor (Blumthaler et al. 1996; Blumthaler 2012). These authors showed

that under a clear sky in summer, UV-A increases by about 9 % per 1,000 m and UV-B by 18 % per 1,000 m. In addition, Blumthaler and Ambach (1990) found evidence for an increasing trend of UV-B in the Alps, due to stratospheric ozone depletion. Consequently, high-alpine ecosystems and their communities such as BSCs experience seasonally fluctuating enhanced desiccation and UVR conditions. While adaptive strategies in higher plants of the Alps and other mountains have been intensively studied (Larcher 2003; Körner 2003; Holzinger et al. 2007; Lütz and Engel 2007, and references therein), corresponding data on BSC algae from these areas are still very limited (Türk and Gärtner 2001; Karsten et al. 2010, 2013; Karsten and Holzinger 2012), but particularly interesting, as UVR can act as a destructive factor on exposed green algae (Holzinger and Lütz 2006).

The length and width of the LGK-974 purchase tumors were measured using a caliper every PXD101 other day. The tumor size was calculated according to the following formula: Tumor volume (mm3) = (length × width2)/2. Tumor growth curves were drawn based on tumor size. All TA2 mice were sacrificed on the 18th day after injection of the cells and the tumor masses were removed. Parts of the tumor without necrosis were collected and stored at −80°C and the remainder of the tumors were fixed with 10% formalin

and embedded in paraffin for H&E and immunohistochemical staining. Immunohistochemical staining Four μm thick paraffin-embedded tissue sections were cut and stained immunohistochemically. The sections were deparaffinized with xylene and rehydraded through graded alcohols. Endogenous peroxidase was blocked with 3% hydrogen peroxide in 50% methanol at room temperature for 10 min. The primary antibodies were diluted to 1:100. Torin 2 molecular weight The tissue sections were heated in a microwave oven in citrate buffer for about 20 min. The slides were incubated with primary antibodies MMP9 (goat polyclonal, Santa Cruz, sc-6840,1:100) and PCNA (goat polyclonal, Santa Cruz, sc-9857,1:100) overnight at 4°C, washed with PBS, and incubated with the biotinylated secondary antibody and preformed

avidin-biotinylated peroxidase complex. The color was developed with DAB. Finally, all of the sections were counterstained with hematoxylin. Human breast cancer was used as a positive control and PBS was used in place of primary antibody to serve as a negative control. Real-time PCR to detect Methane monooxygenase MMP9 mRNA expression levels Total RNA from the fresh TA2 tumor samples was extracted with Trizol reagent according to the manufacturer’s instructions. The integrity and purity of isolated RNA were confirmed with

1% agarose gel electrophoresis and OD260/OD280 ratio. Complementary DNA (cDNA) was synthesized and amplified from total RNA using the Access real time PCR system (TaKaRa One Step RNA PCR Kit). The primer sequences used in the reaction are listed in Additional file 1: Table S1. The resultant cDNA products of MMP9 and β-actin were 86 and 174 base pairs, respectively. The products of RT PCR were purified with TaKaRa Agarose Gel DNA Purification Kit Ver.2.0. Real time PCR products were analyzed with the Gene AMP PCR System 5700 Sequence Detector. The size of the real-time PCR products was validated with 1.5% agarose gel electrophoresis. The CT value (the cycle number at which the fluorescence crosses the threshold) was determined and the formula 2^(−ΔΔCT) was used to determine the relative quantity of the amplified fragment, where ΔΔCT = ΔCT MMP9-ΔCT β-actin was defined as the relative quantity of the amplified fragment. Every sample was tested in triplicate and the mean value was used.

In this sense, one might also speculate that the hypothetical proteins identified as non variant in the two strains may have functions associated to the general physiology of C. pseudotuberculosis, when grown in minimal medium. The most up-regulated proteins were observed in the extracellular proteome of the C231 strain, including two cell envelope-associated proteins [62], namely the major secreted (mycoloyltransferase) protein

PS1 (10-fold up-regulated), and the S-layer protein A (8-fold up-regulation) (Figure 3). This may be indicative of differences on cell envelope-related activities in the two C. pseudotuberculosis strains, such as nutrient acquisition, protein export, adherence and interaction with the host [63]. Dumas et al. [49] compared the exoproteomes of Listeria monocytogenes strains of different virulence find more groups, and found that altered expression (up- or down-regulation) of a protein related to the bacterial cell wall could be a marker of specific virulence phenotypes.

Additionally, surface associated proteins have been IWR-1 research buy shown to undergo phase and antigenic variation in some bacterial pathogens, and ultimately affect the infectivity potential of different strains [50]. Comparative analyses of corynebacterial exoproteomes Recent studies attempted to characterize the extracellular proteomes of other pathogenic (C. diphtheriae and C. jeikeium) and non-pathogenic (C. glutamicum and C. efficiens) corynebacterial species [17, 37, 64, 65]. All these studies

used 2D-PAGE to resolve the extracellular proteins of the different corynebacteria, and PMF by MALDI-TOF-MS was the method of choice in most of them for protein identification [17, 37, 64, 65]. Figure 4 shows the numbers of proteins identified in the exoproteomes of all strains studied, in comparison to the numbers obtained in the present study for C. pseudotuberculosis. Despite one study with the learn more strain R of C. glutamicum, Interleukin-3 receptor which reports identification of only two secreted proteins [65], all the corynebacterial strains had somehow similar numbers of extracellular proteins identified, ranging from forty-seven in C. jeikeium K411 to seventy-four in C. diphtheriae C7s(-)tox-. Importantly, the fact that we have identified in this study 93 different exoproteins of C. pseudotuberculosis, through the analysis of two different strains, means that our dataset represents the most comprehensive exoproteome analysis of a corynebacterial species so far. Figure 4 Comparative analysis of corynebacterial exoproteomes. Numbers of extracellular proteins identified in previous corynebacterial exoproteome analyses [17, 37, 69, 70] in comparison to those identified in this study with the two strains of C. pseudotuberculosis.

(DOC 703 KB) References 1. Lamont RJ, Jenkinson HF: Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev 1998, 62:1244–1263.PubMed A-769662 cell line 2. Griffen AL, Becker MR, Lyons SR, Moeschberger ML, Leys EJ: Prevalence of Porphyromonas gingivalis and periodontal health status. J Clin Microbiol 1998, 36:3239–3242.PubMed 3. Chun YH, Chun KR, Olguin D, Wang HL: Biological foundation for periodontitis as a potential risk factor for atherosclerosis. J Periodontal Res 2005, 40:87–95.CrossRefPubMed 4. Offenbacher S, Jared HL, O’Reilly PG, Wells SR, Salvi

GE, Lawrence HP, Socransky SS, Beck JD: Potential pathogenic mechanisms of periodontitis associated pregnancy complications. Ann Periodontol 1998, 3:233–250.CrossRefPubMed 5. Shah H, Gharbia S: Batch culture and physiological properties. Biology of the species Porphyromonas gingivalis (Edited by: Shah HN, Mayrand D, Genco RJ). Florida: Boca Raton CRC Press Inc 1993, 85–103. 6. Holt SC, Kesavalu L, Walker S, Genco CA: Virulence factors of Porphyromonas gingivalis. Periodontol 2000 1999, 20:168–238.CrossRefPubMed 7. O’Brien-Simpson N, Veith PD, Dashper SG, Reynolds EC:Porphyromonas gingivalis gingipains: the molecular teeth of a microbial vampire. SAHA HDAC chemical structure Curr Protein Pept Sci 2003, 4:409–426.CrossRef 8. Chen W, Palmer RJ, Kuramitsu

HK: Role of polyphosphate kinase in biofilm selleckchem formation by Porphyromonas gingivalis. Infect Immun 2002, 70:4708–4715.CrossRefPubMed Ixazomib supplier 9. Davey ME, Duncan MJ: Enhanced biofilm formation and loss of capsule synthesis:

deletion of a putative glycosyltransferase in Porphyromonas gingivalis. J Bacteriol 2006, 188:5510–5523.CrossRefPubMed 10. Kuramitsu HK, Chen W, Ikegami A: Biofilm formation by the periodontopathic bacteria Treponema denticola and Porphyromonas gingivalis. J Periodontol 2005, 76:2047–2051.CrossRefPubMed 11. Lin X, Wu J, Xie H:Porphyromonas gingivalis minor fimbriae are required for cell-cell interactions. Infect Immun 2006, 74:6011–6015.CrossRefPubMed 12. Nakao R, Senpuku H, Watanabe H:Porphyromonas gingivalis galE is involved in lipopolysaccharide O-antigen synthesis and biofilm formation. Infect Immun 2006, 74:6145–6153.CrossRefPubMed 13. Capestany CA, Kuboniwa M, Jung IY, Park Y, Tribble GD, Lamont RJ: Role of the Porphyromonas gingivalis InlJ protein in homotypic and heterotypic biofilm development. Infect Immun 2006, 74:3002–3005.CrossRefPubMed 14. Chen W, Honma K, Sharma A, Kuramitsu HK: A universal stress protein of Porphyromonas gingivalis is involved in stress responses and biofilm formation. FEMS Microbiol Lett 2006, 264:15–21.CrossRefPubMed 15. Ang CS, Veith PD, Dashper SG, Reynolds EC: Application of 16 O/ 18 O reverse proteolytic labeling to determine the effect of biofilm culture on the cell envelope proteome of Porphyromonas gingivalis W50. Proteomics 2008, 8:1645–1660.CrossRefPubMed 16.

In contrast, similarly treated conidia of mutants strain showed significantly

(P < 0.001) higher germination rates (82%, 64% and 56%) (Figure 5B). However, no differences in conidial germination between either of single or double deletion mutants were found in any of the stress condition tested (Figure 5). Figure 5 Abiotic stress tolerances of C . rosea WT and mutant strains. A: Frequency of conidia germination on medium containing NaCl, sorbitol, SDS, or caffeine as abiotic stress agents. Conidia spread on PDA plate were served as control. B: Frequency of conidia germination Cilengitide after cold shock at 4°C for 3 days, 6 days or 9 days. C. rosea WT, mutants and complementation buy CH5424802 strains conidia were spread on agar plates and frequency of conidial germination was determined by counting two hundred to three hundred conidial germ-tubes or conidia under microscope for each treatment. Each experiment was repeated KU55933 cost two times. Error bars represent standard deviation based on 3 biological replicates. Different letters indicate statistically significant differences

(P ≤ 0.05) based on the Tukey-Kramer test. Deletion of Hyd1 and Hyd3 did not affect Hyd2 expression In order to examine whether or not deletion of Hyd1 and Hyd3, individually or simultaneously, affects the expression pattern of Hyd2, RNA was extracted from conidiating mycelium of WT and mutant strains grown on PDA plates. Gene expression analysis revealed no significant difference in Hyd2 expression between WT and either single or double deletion strains (Additional file 1: Figure S5). In vitro assay to test the antagonistic ability of C. rosea strains The ΔHyd1, ΔHyd3, and ΔHyd1ΔHyd3 strains overgrew B. cinerea, F. graminearum and Rhizoctonia solani faster than the WT in plate confrontation assays (Figure 6A).

The complemented strains ΔHyd1+ ΔHyd3+ showed partial restoration of WT behaviour. Furthermore, in order to understand the tolerance of C. rosea strains to the secreted metabolites from the fungal prey, a secretion assay was performed. Growth rates of deletion strains were significantly (P < 0.001) higher than the WT when 4��8C grown on agar plates where B. cinerea, F. graminearum or R. solani were pregrown (Figure 6B). In addition, the double deletion strain ΔHyd1ΔHyd3 showed significantly (P ≤ 0.05) higher growth rate compared to the either single deletion mutant (Figure 6B). Similarly to the plate confrontation assay, ΔHyd1+ and ΔHyd3+ strains showed partial restoration of WT growth rates. Figure 6 Antagonism analyses of C . rosea strains. A: Plate confrontation assay against B. cinerea (Uppar lane), R. solani (middle lane) and F. graminearum (lower lane). Agar plugs of C. rosea (left side in the plate) strains and B. cinerea, R. solani or F.

The

exact mechanism for the inverse association between the HIF-1α 1790 G/A polymorphism and breast cancer was not clear. However, there were two factors that must be considered. First, the frequency of the HIF-1α 1790 A allele was very low and only two studies were included in the breast cancer subgroup. So, the association could be due to chance. Second, our find more meta-analysis suggests that carcinogenic mechanism may differ in different cancers and HIF-1α 1790 G/A polymorphism may exert varying effect. More studies will be required to further examine the association. The current meta-analysis has several limitations which should be noted. First, BI 2536 molecular weight the meta-analysis was based on the aggregation of published case-control studies. 8 studies did not clearly state the use of a matching design for cases during the selection process of controls. The meta-analysis was based on unadjusted estimates. A more precise analysis should be conducted if more detailed individual data were available, which would allow for an adjusted estimate. Second, because of data limitation, we did not perform the stratification analyses by age, smoking, or other variables. Third, several genotyping methods were used in the eligible studies. The quality control of genotyping was not well documented in some studies. Undoubtedly, the limitations

mentioned should affect our final conclusions. Conclusions Our meta-analysis suggests that the HIF-1α 1772 C/T polymorphism is significantly associated with higher cancer risk, and the 1790 G/A polymorphism Torin 1 chemical structure is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and

female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased fantofarone risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance. Acknowledgements This work was supported by National Natural Science foundation of China (Grant No: 30671007) and Natural Science foundation of Zhejiang Province, China (Grant No: Y2081111). Electronic supplementary material Additional file 1: The flow diagram of included/excluded studies. (JPEG 250 KB) Additional file 2: Characteristics of individual studies included in the meta-analysis. (DOC 62 KB) Additional file 3: Genotype and allele distribution of hypoxia- inducible factor -1α 1772 C/T and 1790 G/A polymorphisms of individual studies included in the meta-analysis. (DOC 69 KB) Additional file 4: Funnel plots for publication bias test. A. HIF-1α 1772 C/T: T versus C. B. HIF-1α 1790 G/A: A versus G. Each point represents a separate study for the indicated association. SE(SMD), standard error of the logarithm of the odd ratio. (JPEG 189 KB) References 1.

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