Zurich Open Repository and Archive. Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population
|
|
- Jesse Carson
- 6 years ago
- Views:
Transcription
1 University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich Year: 2010 Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population Kurzwelly, D; Knop, S; Guenther, M; Loeffler, J; Korfel, A; Thiel, E; Hebart, H; Simon, M; Weller, M; Linnebank, M; Herrlinger, U Kurzwelly, D; Knop, S; Guenther, M; Loeffler, J; Korfel, A; Thiel, E; Hebart, H; Simon, M; Weller, M; Linnebank, M; Herrlinger, U (2010). Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population. Journal of Neuro-Oncology, 100(2): Postprint available at: Posted at the Zurich Open Repository and Archive, University of Zurich. Originally published at: Kurzwelly, D; Knop, S; Guenther, M; Loeffler, J; Korfel, A; Thiel, E; Hebart, H; Simon, M; Weller, M; Linnebank, M; Herrlinger, U (2010). Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population. Journal of Neuro-Oncology, 100(2):
2 Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population Abstract Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-hodgkin's lymphoma. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight genetic polymorphisms affecting methionine metabolism for potential association with the development of PCNSL. We observed underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine S-methyltransferase (MTR) c.2756a > G (D919G) missense polymorphism among PCNSL patients (P = 0.045; odds ratio (OR) = 0.65; ). Furthermore, for the methylenetetrahydrofolate reductase (MTHFR) c.1298a > C (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients than among population controls (P = 0.026; OR = 1.57; ). There were no associations of the other polymorphisms investigated (MTHFR c.677c > T, transcobalamin 2 (Tc2) c.776c > G, cystathionin beta-synthase (CBS) c.844_855ins68, reduced folate carrier-1 (RFC-1) c.80g > A, thymidylate synthase (TYMS) 28-bp repeat, and dihydrofolate reductase (DHFR) c del19 bp) and the presence of PCNSL. This analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant to susceptibility to PCNSL.
3 Running head: Folate metabolism and PCNSL Genetic variants of folate and methionine metabolism and PCNSL incidence in a German patient population Delia Kurzwelly 1, Stefan Knop 2, Markus Guenther 3, Juergen Loeffler 2, Agnieszka Korfel 4, Eckhard Thiel 4, Holger Hebart 5, Matthias Simon 6, Michael Weller 7, Michael Linnebank 7, Ulrich Herrlinger 1 1 Division of Clinical Neurooncology, Department of Neurology, University of Bonn, Sigmund-Freud-Str. 25, D Bonn, Germany 2 Department of Hematology and Oncology, Wuerzburg University Hospital, Josef-Schneider- Straße 2, D Wuerzburg, Germany 3 Department of Internal Medicine, Klinikum Stuttgart, Prießnitzweg 24, Stuttgart, Germany 4 Department of Hematology and Oncology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, D Berlin, Germany 5 Department of Internal Medicine, Klinikum Schwaebisch Gmuend Stauferklinik, Wetzgauer Straße 85, D Mutlangen, Germany 6 Department of Neurosurgery, University of Bonn, Sigmund-Freud-Str. 25, D Bonn, Germany 7 Department of Neurology, University Hospital Zurich, Frauenklinikstraße 26, CH-8091 Zurich, Switzerland
4 Correspondence to: Ulrich Herrlinger, MD, Division of Clinical Neurooncology, Department of Neurology, University of Bonn, Sigmund-Freud-Str. 25, D Bonn, Germany. Tel.: ; Fax: ; Abstract Functional genetic polymorphisms involved in folate and methionine metabolism play an important role in both DNA synthesis and methylation, and affect the risk of various malignancies including lymphoproliferative disorders such as systemic non-hodgkin s lymphoma. In a retrospective analysis of 185 immunocompetent patients with primary central nervous system lymphoma (PCNSL) and 212 population controls we therefore investigated eight genetic polymorphisms influencing methionine metabolism for a potential association with the development of PCNSL. We observed an underrepresentation of the G-allele of the methyltetrahydrofolate homocysteine S-methyltransferase (MTR) c.2756a>g (D919G) missense polymorphism among PCNSL patients (p=0.045; odds ratio [OR]=0.65; ). Furthermore, for the methylenetetrahydrofolate reductase (MTHFR) c.1298a>c (E429A) polymorphism the mutated C-allele was found more frequently among PCNSL patients in comparison to population controls (p=0.026; OR=1.57; ). There were no associations of the other polymorphisms investigated [MTHFR c.677c>t, transcobalamin 2 (Tc2) c.776c>g, cystathionin beta-synthase (CBS) c.844_855ins68, reduced folate carrier-1 (RFC-1) c.80g>a, thymidylate synthase (TYMS) 28-bp repeat, and dihydrofolate reductase (DHFR) c del19bp] and the presence of PCNSL. 2
5 The present analysis is the largest to date to evaluate associations between genetic variants of folate and methionine metabolism and PCNSL. Our results suggest the hypothesis that folate and methionine metabolism is relevant for the susceptibility to PCNSL. Keywords: Genetic polymorphism - Folate - Methionine - DNA methylation - PCNSL 3
6 Introduction Primary central nervous system lymphoma (PCNSL) is an aggressive subtype of non- Hodgkin s lymphoma (NHL) arising within the central nervous system (CNS). The vast majority are diffuse large B-cell lymphomas (DLBCL) derived from germinal center B cells [1], and pathogenic factors are largely unclear, so far. In a recent retrospective analysis no association between PCNSL and human leukocyte antigens (HLA) was found [2]. PCNSL characteristically reveals genetic instability with chromosomal imbalances [3]. Thus, metabolic factors and conditions contributing to the maintenance of DNA integrity may be influential for the development and growth of PCNSL cells via altered DNA synthesis and methylation of oncogenes and tumor suppressor genes. Aberrant folate and methionine metabolism could interfere with both processes. Genetic variants that functionally influence enzymes, transporter proteins or receptor proteins involved in folate and methionine metabolism are associated with different types of extracranial human cancer, such as systemic NHL, acute leukemia, and colorectal cancer [4-8]. In immunocompetent patients, an association of PCNSL with the methyltetrahydrofolate homocysteine S-methyltransferase (MTR) c.2756a>g variant has been reported [9], and this polymorphism has also been described to alter susceptibility to other intracranial tumors including glioblastoma and anaplastic meningioma [10, 11]. In the present explorative study we aimed to analyze the frequency of eight functional genetic variants of folate and methionine metabolism in a collective of 185 patients with PCNSL compared with 212 healthy controls, making this study the largest to date to evaluate this association. 4
7 Materials and methods Study population We investigated 185 consecutive immunocompetent PCNSL patients of Caucasian origin recruited for the German multicenter phase IV trial (G-PCNSL-SG-1) between 08/2000 and 12/2004 (43.8% female; median age at diagnosis 60.4 years, range years). The aim of the G-PCNSL-SG-1 study is to analyze the value of whole brain radiotherapy after 6 courses of high-dose methotrexate (MTX) in newly diagnosed PCNSL. Inclusion criteria for the G- PCNSL-SG-1 study were a newly diagnosed and histologically or cytologically (in the cerebrospinal fluid) confirmed PCNSL in an immunocompetent patient and adequate renal and bone marrow function. Exclusion criteria were systemic manifestation of NHL and additional malignancies as well as immunodeficiency or concomitant immunosuppressive therapy. 212 apparently healthy Caucasian Bonn area residents (45.8% female; median age 63.0 years, range years) without a history of cancer, recruited as control population for an ongoing study on atherosclerosis, served as controls [12, 13]. The same collective had already been used as control group for a small case-control study analyzing folatemetabolizing pathway polymorphisms in patients with PCNSL [9]. Characteristics of the study population have also been summarized in Table 1. The study was approved by the respective local ethics committees, and all participants gave written informed consent. DNA extraction and genotyping Blood samples were collected prospectively upon enrollment onto the G-PCNSL-SG-1 trial before treatment was started. Genomic DNA was extracted from mononuclear cells using the QIAamp DNA Blood Mini Kit (Qiagen, Hilden, Germany). Genotyping of eight polymorphisms [methylenetetrahydrofolate reductase (MTHFR) c.677c>t (A222V), MTHFR c.1298a>c (E429A), MTR c.2756a>g (D919G), transcobalamin 2 (Tc2) c.776c>g (P259R), 5
8 cystathionin beta-synthase (CBS) c.844_855ins68 (change of transcript levels), reduced folate carrier-1 (RFC-1) c.g80a (R27H), thymidylate synthase (TYMS) 28bp rep (2R>3R), dihydrofolate reductase (DHFR) c del19bp (change of transcript levels)] was performed by amplification of genomic DNA applying polymerase chain reaction (PCR) and subsequent restriction enzyme digestion or by allele specific PCR, followed by agarose gel electrophoresis [14-20]. Statistical analysis The distribution of age and gender in the patient and the control collective was compared applying t-test for two independent samples and Pearson`s Chi 2 test, respectively. For the tested genotypes the Hardy-Weinberg equation was calculated for all PCNSL patients and controls together with a Chi 2 goodness-of-fit test (df=2). The two-sided Pearson`s Chi 2 test was used to analyze the distribution of the respective genotypes in the patient and the control group for statistical significance. Threshold was defined with alpha <0.05. Due to the low frequencies of the MTR c.2756gg and the MTHFR c.1298cc homozygous variants, we additionally evaluated the presence of at least one mutant allele (AG/GG or AC/CC) versus homozygosity for the wildtype allele (AA) in the patient and the control sample (Pearson`s Chi 2 test; df=1). All analyses were purely explorative, so that correction for multiple testing was not regarded necessary, and all findings require reevaluation in future studies. Odds ratios (OR) together with 95% confidence intervals (CI) were calculated for the combined MTR c.2756ag/gg and MTHFR c.1298ac/cc genotypes, respectively. Furthermore, multinominal regression analysis with alpha=0.05 was applied to test the independent association of the respective polymorphisms with PCNSL and to exclude confounding effects of age, gender, or multiple testing. All statistical calculations were performed using the Statistical Package for the Social Sciences ( SPSS ) software version 16.0 (SPSS, Chicago, IL, USA). 6
9 Results There were no significant differences concerning age and gender between the patient and the control cohort. Genotype distributions in all PCNSL patients and controls are shown in Table 2. The distribution of allelotypes of the polymorphisms did not significantly deviate from the Hardy-Weinberg equilibrium (data not shown). Allelic frequencies of the MTHFR c.677c>t, MTHFR c.1298a>c, MTR c.2756a>g, Tc2 c.776c>g, CBS c.844_855ins68, RFC-1 c.80g>a, TYMS 28-bp repeat, and the DHFR c del19bp polymorphism in the control group are similar to those found in another independent healthy German population [21] and those reported for other Caucasian populations [15, 16, 22]. The MTR c.2756a>g polymorphism (G-allele) was less frequent in PCNSL patients than in controls (patients AA/AG/GG: 71.3/24.9/3.8 and controls AA/AG/GG: 61.8/34.0/4.2; Chi 2 =4,17 (Pearson), p=0.125 for trend, df=2). In Pearson`s Chi 2 test of the pooled genotypes MTR c.2756aa versus AG/GG without correction for multiple testing, the MTR c.2756g allele was significantly underrepresented in the patient sample; at least one mutant allele (the MTR c.2756ag and GG genotypes) was detected in 28.7% of PCNSL patients compared to 38.2% of controls (Chi 2 =4.04, p=0.045, df=1; Table 3). Overall, multinominal logistic regression analysis with simultaneous analysis of all eight polymorphisms together with age and gender as co-variables reproduced the above findings (Chi 2 =4.449, p=0.035 for pooled genotypes, df=1). Furthermore, for the MTHFR c.1298a>c polymorphism, the mutated C-allele was observed more frequently among PCNSL patients than in controls (patients AA/AC/CC: 38.8/52.1/9.1 and controls AA/AC/CC: 50.5/42.0/7.5; Chi 2 =5.38 (Pearson), p=0.068 for trend, df=2). This trend was significant in the uncorrected explorative analysis (MTHFR c.1298aa versus AC 7
10 and CC genotypes: Chi 2 =5.00, p=0.026, df=1; Table 3) as well as in multinomial logistic regression analysis of the pooled genotypes (Chi 2 =5.179, p=0.023). A reduced risk estimate was found for the MTR c.2756ag/gg genotype when MTR c.2756aa was the referent group (OR=0.65; ; Table 3), whereas a small increased risk estimate for PCNSL was associated with the MTHFR c.1298ac/cc genotype versus homozygosity for the wildtype allele AA (OR=1.57; ; Table 3). There were no significant associations of the other polymorphisms investigated (MTHFR c.677c>t, Tc2 c.776c>g, CBS c.844_855ins68, RFC-1 c.80g>a, TYMS 28-bp repeat, and DHFR c del19bp; Table 2) and the development of PCNSL. Discussion The findings presented here suggest an association between the MTR c.2756a>g (D919G) as well as the MTHFR c.1298a>c (E429A) polymorphisms and the presence of PCNSL, with the MTR c.2756g allele being less frequent, and the mutated MTHFR c.1298c allele more common in patients than in population controls. As for the MTR c.2756a>g polymorphism these data confirm the results of a previous casecontrol study on 31 German PCNSL patients which found significantly fewer carriers of the MTR c.2756a>g missense polymorphism among the patients [9]. Of note, control samples of both studies overlap, so the observed effect could have been due to a coincidental overrepresentation of the G-allele in the control group. However, this seems unlikely, as allelic frequencies of the MTR c.2756a>g polymorphism in this control group are similar to those of another independent healthy German population [21]. Interestingly, in this population 8
11 sample the presence of the MTR c.2756g allele has been correlated with disease-free longevity. MTR catalyzes the remethylation of homocysteine to methionine. The G-allele of MTR c.2756a>g has been suggested to lead to a higher MTR activity, supposedly changing the kinetics of nucleic acid and S-adenosylmethionine (SAM) synthesis. SAM is necessary for DNA methylation. Thus, the MTR variant may influence both DNA synthesis and methylation, whereas any concrete influence of the variant on tumorigenesis remains speculative. Our results showing a reduced frequency of the MTR c.2756g allele in patients with PCNSL are in line with previous studies on the MTR missense dimorphism c.2756a>g which found a lower frequency in patients with colorectal cancer [7], cervical intraepithelial neoplasia [23] and follicular NHL [8], and (among primary brain tumors) with GBM and anaplastic meningioma [10, 11]. The second genetic variant in this study, MTHFR c.1298a>c, with a significant positive association with PCNSL in explorative data analysis has previously been reported to be associated with some types of human cancer [4-6, 24]. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which acts as a methyl donor for the transformation of homocysteine to methionine. Both polymorphisms in the MTHFR gene, c.677c>t and c.1298a>c, lead to reduced enzyme activity. While these variants were both observed more frequently in our patient group, this effect did not reach statistical significance for the MTHFR c.677c>t polymorphism. That could be due to a too small sample size and should be reevaluated in further patient collectives, although PCNSL is a rare disease, and large patient cohorts are difficult to obtain. Possible mechanisms underlying an association of the MTHFR variants include effects on folate derivatization, on homocysteine remethylation to methionine and on SAM availability for DNA synthesis. More basic research is necessary to elucidate such putative interactions. 9
12 However, as pointed out, the reported variants do not exclusively affect pathways in PCNSL development but are apparently relevant for tumorigenesis in general. Moreover, due to the case-control design of our study, and due to the "matching procedure" we employed (which was not done between individual cases and controls, but between the entire group of cases and the entire group of controls) certain caveats are necessary, including the possibility of unrecognized selection bias and unknown confounders which cannot be fully controlled for. As a result, a definitive relationship between "exposure" (i.e. MTR and MTHFR polymorphisms) and PCNSL has not been established. This study is an explorative, hypothesis-generating investigation. Our results require replication in additional large trials and in pooled analyses. In summary, the present analysis is the largest to date to evaluate associations between polymorphisms in folate-metabolizing genes and PCNSL, and suggests that certain functional genetic variants of folate and methionine metabolism alter susceptibility to PCNSL. Specifically, the MTR c.2756g allele may reduce susceptibility (a protective effect) while the MTHFR c.1298c allele may increase susceptibility. Since folate and methionine metabolism is closely associated with the availability of methionine, folate and vitamin B12, it might even be possible that nutritional factors modify the incidence of PCNSL, as has been described for other tumors. Folate and methionine metabolism also seems to affect anticancer therapy with MTX which is still the most efficient chemotherapy component in the treatment of PCNSL and directly interferes with methionine metabolism. Therefore, further studies on the impact of folate and methionine metabolism on incidence and treatment outcome of PCNSL are warranted. 10
13 Acknowledgment: This study was generously supported by a grant from the Fortune Program of the University of Tuebingen Medical School to S. Knop, H. Hebart, and U. Herrlinger and a Deutsche Krebshilfe grant ( Th2) to U. Herrlinger, A. Korfel, E. Thiel, and M. Weller. References 1. Montesinos-Rongen M, Küppers R, Schlüter D, Spieker T, Van Roost D, Schaller C, Reifenberger G, Wiestler OD, Deckert-Schlüter M (1999) Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment. Am J Pathol 155: Kurzwelly D, Müller CA, Korfel A, Thiel E, Linnebank M, Weller M, Herrlinger U (2008) Primary CNS lymphoma and HLA class I and II alleles in a German cohort of immunocompetent patients. J Neurooncol 90: Weber T, Weber RG, Kaulich K, Actor B, Meyer-Puttlitz B, Lampel S, Büschges R, Weigel R, Deckert-Schlüter M, Schmiedek P, Reifenberger G, Lichter P (2000) Characteristic chromosomal imbalances in primary central nervous system lymphomas of the diffuse large B-cell type. Brain Pathol 10: Sharp L, Little J (2004) Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 159: Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cartwright RA, Morgan G (1999) Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci USA 96: Matsuo K, Suzuki R, Hamajima N, Ogura M, Kagami Y, Taji H, Kondoh E, Maeda S, Asakura S, Kaba S, Nakamura S, Seto M, Morishima Y, Tajima K (2001) Association 11
14 between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma. Blood 97: Ma J, Stampfer MJ, Christensen B, Giovannucci E, Hunter DJ, Chen J, Willett WC, Selhub J, Hennekens CH, Gravel R, Rozen R (1999) A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocysteine, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 8: Lincz LF, Scorgie FE, Kerridge I, Potts R, Spencer A, Enno A (2003) Methionine synthase genetic polymorphism MS A2756G alters susceptibility to follicular but not diffuse large B-cell non-hodgkin`s lymphoma or multiple myeloma. Br J Haematol 120: Linnebank M, Schmidt S, Kölsch H, Linnebank A, Heun R, Schmidt-Wolf IG, Glasmacher A, Fliessbach K, Klockgether T, Schlegel U, Pels H (2004) The methionine synthase polymorphism D919G alters susceptibility to primary central nervous system lymphoma. Br J Cancer 90: Semmler A, Simon M, Moskau S, Linnebank M (2006) The methionine synthase polymorphism c.2756a>g alters susceptibility to glioblastoma multiforme. Cancer Epidemiol Biomarkers Prev 15: Semmler A, Simon M, Moskau S, Linnebank M (2008) Polymorphisms of methionine metabolism and susceptibility to meningioma formation: laboratory investigation. J Neurosurg 108: Moskau S, Golla A, Grothe C, Boes M, Pohl C, Klockgether T (2005) Heritability of carotid artery atherosclerotic lesions: an ultrasound study in 154 families. Stroke 36: Linnebank M, Moskau S, Farmand S, Fliessbach K, Kölsch H, Bös M, Grothe C, Becker D, Harbrecht U, Pohl C, Wüllner U, Klockgether T (2006) Homocysteine and carotid 12
15 intima-media thickness in a German population: Lack of clinical relevance. Stroke 37: Afman LA, Lievers KJ, van der Put NM, Trijbels FJ, Blom HJ (2002) Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects. Eur J Hum Genet 10: Harmon DL, Shields DC, Woodside JV, McMaster D, Yarnell JW, Young IS, Peng K, Shane B, Evans AE, Whitehead AS (1999) Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations. Genet Epidemiol 17: Linnebank M, Homberger A, Junker R, Nowak-Goettl U, Harms E, Koch HG (2001) High prevalence of the I278T mutation of the human cystathionine ß-synthase detected by a novel screening application. Thromb Haemost 85: Johnson WG, Stenroos ES, Spychala JR, Chatkupt S, Ming SX, Buyske S (2004) New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR): a risk factor for spina bifida acting in mothers during pregnancy? Am J Med Genet A 124: Winkelmayer WC, Eberle C, Sunder-Plassmann G, Fodinger M (2003) Effects of the glutamate carboxypeptidase II (GCP2 1561C>T) and the reduced folate carrier (RFC1 80G>A) allelic variants on folate and total homocysteine levels in kidney transplant patients. Kidney Int 63: Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuve LP, Rozen R (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10: van der Put NM, Gabreëls F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, van den Heuvel LP, Blom HJ (1998) A second common mutation in the 13
16 methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 62: Linnebank M, Fliessbach K, Kolsch H, Rietschel M, Wullner U (2005) The methionine synthase polymorphism c.2756a>g (D919G) is relevant for disease-free longevity. Int J Mol Med 16: Linnebank M, Homberger A, Nowak-Gottl U, Marquardt T, Harms E, Koch HG (2000) Linkage disequilibrium of the common mutations 677C>T and 1298A>C of the human methylenetetrahydrofolate reductase gene as proven by the novel polymorphisms 129C>T, 1068C>T. Eur J Pediatr 159: Henao OL, Piyathilake CJ, Waterbor JW, Funkhouser E, Johanning GL, Heimburger DC, Partridge EE (2005) Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3. Int J Cancer 113: Wiemels JL, Smith RN, Taylor GM, Eden OB, Alexander FE, Greaves MF; United Kingdom Childhood Cancer Study investigators (2001) Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA 98:
17 Table 1 Characteristics of patients with primary central nervous system lymphoma (PCNSL) and control individuals Characteristics PCNSL Controls No. (%) Median (Range) No. (%) Median (Range) No. of individuals Demographic data Male 104 (56.2) (54.2) - Female 81 (43.8) - 97 (45.8) - Age at diagnosis [years] (18-81) (39-85) Descent Caucasian Caucasian Prior therapy None -
18 Table 3 Pearson`s Chi 2 analysis, odds ratios (OR), and 95% confidence intervals (CI) of the pooled genotypes MTR c.2756ag/gg vs. AA and MTHFR c.1298ac/cc vs. AA in PCNSL patients and controls Genotype PCNSL (n = 185) Controls (n = 212) MTR c.2756a>g χ 2 (df = 1) P (χ 2 ) OR (95% CI) AA AG or GG ( ) MTHFR c.1298a>c χ 2 P OR (95% CI) AA AC or CC ( ) The distribution of the different genotypes among PCNSL patients and controls is given as relative amount.
19 Table 2 Distribution of polymorphisms involved in folate-metabolizing pathway genes in patients with primary central nervous system lymphoma (PCNSL) and controls: Pearson`s Chi 2 analysis MTHFR c.677c>t CC CT TT χ 2 (df = 2) P (χ 2 ) PCNSL (n = 185) Controls (n = 212) MTHFR c.1298a>c AA AC CC χ 2 P PCNSL (n = 185) Controls (n = 212) RFC c.80g>a GG GA AA χ 2 P PCNSL (n = 185) Controls (n = 212) TYMS 28-bp repeat (2R>3R) 2R / 2R 2R / 3R 3R / 3R χ 2 P PCNSL (n = 185) Controls (n = 212) MTR c.2756a>g AA AG GG χ 2 P PCNSL (n = 185) Controls (n = 212) DHFR c del19-bp ins / ins ins / del del / del χ 2 P PCNSL (n = 185) Controls (n = 212) CBS c.844_855ins68 del /del del / ins ins / ins χ 2 P PCNSL (n = 185) Controls (n = 212) Tc2 c.776c>g CC CG GG χ 2 P PCNSL (n = 185) Controls (n = 212)
20 The rate of carriers of the different genotypes is given as relative amount. The Chi 2 test values for Pearson`s Chi 2 test for all three genotypes (= two degrees of freedom) for the differences between patients and controls are shown.
Zurich Open Repository and Archive
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2009 Association of genetic variants of methionine metabolism with methotrexate-induced
More informationMETHYLENETETRAHYDROFOLATE REDUCTASE GENE AMONG THE JAPANESE
Jpn J Human Genet 41, 247 251, 1996 Short Communication A COMMON MUTATION IN METHYLENETETRAHYDROFOLATE REDUCTASE GENE AMONG THE JAPANESE POPULATION Hisahide NISHIO, L* Myeong Jin LEE, ~ Motoko FuJlI, 1
More informationFigure 1. Stepwise approach of treating patients with rheumatoid arthritis.
Establish diagnosis early Document baseline disease activity and damage Estimate prognosis Initiate therapy Begin patient education Start DMARD therapy within 3 months Consider NSAID Consider local or
More informationBreast Cancer Risk Associated with Multigenotypic Polymorphisms in Folate-metabolizing Genes: A Nested Case-control Study in Taiwan
Breast Cancer Risk Associated with Multigenotypic Polymorphisms in Folate-metabolizing Genes: A Nested Case-control Study in Taiwan CHENG-PING YU 1, MEI-HSUAN WU 2, YU-CHING CHOU 3, TSAN YANG 4, SAN-LIN
More informationAssociation between MTHFR 677C/T and 1298A/C gene polymorphisms and breast cancer risk
Association between MTHFR 677C/T and 1298A/C gene polymorphisms and breast cancer risk X.F. Zhang 1, T. Liu 2, Y. Li 1 and S. Li 2 1 Department of Breast, Liao Ning Cancer Hospital and Institute, Shenyang,
More informationRelationship between genetic polymorphisms of methylenetetrahydrofolate reductase and breast cancer chemotherapy response
Relationship between genetic polymorphisms of methylenetetrahydrofolate reductase and breast cancer chemotherapy response L. Yang*, X.W. Wang*, L.P. Zhu, H.L. Wang, B. Wang, T. Wu, Q. Zhao, D.L.X.T. JinSiHan
More informationProspective study of MTHFR genetic polymorphisms as a possible etiology of male infertility
Prospective study of MTHFR genetic polymorphisms as a possible etiology of male infertility S.-S. Li 1, J. Li 1, Z. Xiao 2, A.-G. Ren 3 and L. Jin 3 1 Beijing Obstetrics and Gynecology Hospital, Capital
More informationClinical Importance of MTHFR Gene Polymorphism in Coronary Artery Disease: A Study from India
Human Journals Research Article September 2018 Vol.:13, Issue:2 All rights are reserved by Alpana Saxena et al. Clinical Importance of MTHFR Gene Polymorphism in Coronary Artery Disease: A Study from India
More informationMETHYLENETETRAHY- DROFOLATE REDUCTASE GENE POLYMORPHISM IN PATIENTS RECEIVING HEMODIALYSIS
KEY WORDS: Methylenetetrahydrofolate Reductase, C677T polymorphism of the MTHFR gene, hemodialysis & METHYLENETETRAHY- DROFOLATE REDUCTASE GENE POLYMORPHISM IN PATIENTS RECEIVING HEMODIALYSIS Emina Kiseljaković
More informationThe Association Between Methylenetetrahydrofolate Reductase Polymorphism and Promoter Methylation in Proximal Colon Cancer
The Association Between Methylenetetrahydrofolate Reductase Polymorphism and Promoter Methylation in Proximal Colon Cancer KAEKO OYAMA, KAZUYUKI KAWAKAMI, KAZUYA MAEDA, KANAME ISHIGURO and GO WATANABE
More informationAssociation between ERCC1 and ERCC2 polymorphisms and breast cancer risk in a Chinese population
Association between ERCC1 and ERCC2 polymorphisms and breast cancer risk in a Chinese population R. Zhao and M.F. Ying Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University,
More informationC677T polymorphism of the methylenetetrahydrofolate reductase gene does not affect folic acid, vitamin B 12
C677T polymorphism of the methylenetetrahydrofolate reductase gene does not affect folic acid, vitamin B 12, and homocysteine serum levels in Turkish children with neural tube defects M.O. Erdogan 1, S.H.
More informationAssociation of methionine synthase rs and methionine synthase reductase rs polymorphisms with meningioma in adults: A meta analysis
432 Association of methionine synthase rs1801394 and methionine synthase reductase rs1805087 polymorphisms with meningioma in adults: A meta analysis XIAN TAO ZENG 1*, JUN TI LU 2*, XIANG JUN TANG 2*,
More informationAmong the determinants and correlates of total plasma
Genetic Aspects of Hyperhomocysteinemia in Chronic Kidney Disease Gere Sunder-Plassmann, Wolfgang C. Winkelmayer, and Manuela Födinger Patients with chronic kidney disease who are on dialysis or with a
More informationTITLE: Folate and breast cancer: role of intake, blood levels, and Metabolic gene polymorphisms
AD Award Number: DAMD17-02-1-0606 TITLE: Folate and breast cancer: role of intake, blood levels, and Metabolic gene polymorphisms PRINCIPAL INVESTIGATOR: Martha J. Shrubsole, Ph.D. CONTRACTING ORGANIZATION:
More informationIntroduction. Summary
Am. J. Hum. Genet. 64:1045 1055, 1999 The Thermolabile Variant of Methylenetetrahydrofolate Reductase and Neural Tube Defects: An Evaluation of Genetic Risk and the Relative Importance of the Genotypes
More informationArve Ulvik, 1 Stein Emil Vollset, 1 Svein Hansen, 2 Randi Gislefoss, 3 Egil Jellum, 3 and Per Magne Ueland 1. Abstract.
Cancer Epidemiology, Biomarkers & Prevention 2175 Colorectal Cancer and the Methylenetetrahydrofolate Reductase 677C! T and Methionine Synthase 2756A! G Polymorphisms: A Study of 2,168 Case-Control Pairs
More informationGene polymorphisms and Folate metabolism as maternal risk factors for Down syndrome child
Nutrition is a fundamental pillar of human life, health and development across the entire life span. From the earliest stages of fetal development, at birth, through infancy, childhood, adolescence and
More informationHLA-A*26 and Susceptibility of Iranian Patients with Non-Hodgkin Lymphoma
HLA-A*26 and Susceptibility of Iranian Patients with Non-Hodgkin Lymphoma Arezou Sayad 1, Mohammad Taghi Akbari 2**, Mahshid Mehdizadeh 3,4, Mohammad Taheri 1, Abbas Hajifathali 3* 1 Department of Medical
More informationNeural tube defects and MTHFR gene polymorphisms - the incidence in the Slovak population
Neural tube defects and MTHFR gene polymorphisms - the incidence in the Slovak population J. Behunová 1, E.Zavadilíková 1, D. Potočeková 2, Ľ. Podracká 1 1 I. Department of Pediatrics, Safarik University
More informationEditorial. Dietary intake and blood levels of folate, a watersoluble
Editorial Folate and Methylenetetrahydrofolate Reductase Polymorphisms: New Nutritional and Genetic Risk Factors for Pancreatic Cancer? Dietary intake and blood levels of folate, a watersoluble B vitamin
More informationGenetic polymorphisms in the one-carbon metabolism pathway genes and susceptibility to non-hodgkin lymphoma
DOI 10.1007/s13277-014-2785-0 RESEARCH ARTICLE Genetic polymorphisms in the one-carbon metabolism pathway genes and susceptibility to non-hodgkin lymphoma Sujatha Suthandiram & Gin-Gin Gan & Shamsul Mohd
More informationA Second Common Mutation in the Methylenetetrahydrofolate Reductase Gene: An Additional Risk Factor for Neural-Tube Defects?
Am. J. Hum. Genet. 62:1044 1051, 1998 A Second Common Mutation in the Methylenetetrahydrofolate Reductase Gene: An Additional Risk Factor for Neural-Tube Defects? Nathalie M. J. van der Put, 1 Fons Gabreëls,
More information, 73 (2), (2013) * Yuka Moriya DDS. Caspase * Vol. 73, No.
, 73 (2), 111 116 (2013) * Yuka Moriya 3 DDS 3 Caspase 3 *2000 2008 525 8577 1 1 1 E-mail: tomoka@ph.ritsumei.ac.jp 6 2 2 1 Vol. 73, No. 2 (2013) 111 10 CV 4 1 4 MELAS Risk Benefit Benefit % 2001 CsA CsA
More informationIntroduction ORIGINAL INVESTIGATION
Hum Genet (2005) 116: 347 353 DOI 10.1007/s00439-004-1243-2 ORIGINAL INVESTIGATION Carmel Kealey Æ Karen S. Brown Æ Jayne V. Woodside Ian Young Æ Liam Murray Æ Colin A. Boreham Helene McNulty Æ J. J. Strain
More informationInvestigation on ERCC5 genetic polymorphisms and the development of gastric cancer in a Chinese population
Investigation on ERCC5 genetic polymorphisms and the development of gastric cancer in a Chinese population L.Q. Yang 1, Y. Zhang 2 and H.F. Sun 3 1 Department of Gastroenterology, The Second Affiliated
More informationCorporate Medical Policy
Corporate Medical Policy Analysis of MGMT Promoter Methylation in Malignant Gliomas File Name: Origination: Last CAP Review: Next CAP Review: Last Review: analysis_of_mgmt_promoter_methylation_in_malignant_gliomas
More informationAberrant DNA methylation of MGMT and hmlh1 genes in prediction of gastric cancer
Aberrant DNA methylation of MGMT and hmlh1 genes in prediction of gastric cancer J. Jin 1,2, L. Xie 2, C.H. Xie 1 and Y.F. Zhou 1 1 Department of Radiation & Medical Oncology, Zhongnan Hospital of Wuhan
More informationAssociation between interleukin-17a polymorphism and coronary artery disease susceptibility in the Chinese Han population
Association between interleukin-17a polymorphism and coronary artery disease susceptibility in the Chinese Han population G.B. Su, X.L. Guo, X.C. Liu, Q.T. Cui and C.Y. Zhou Department of Cardiothoracic
More informationAssociation between ERCC1 and ERCC2 gene polymorphisms and susceptibility to pancreatic cancer
Association between ERCC1 and ERCC2 gene polymorphisms and susceptibility to pancreatic cancer M.G. He, K. Zheng, D. Tan and Z.X. Wang Department of Hepatobiliary Surgery, Nuclear Industry 215 Hospital
More informationThe Turkish Journal of Pediatrics 2016; 58:
The Turkish Journal of Pediatrics 2016; 58: 152-158 Original Are the methylenetetrahydrofolate reductase 1298 and 677 gene polymorphisms related to optic glioma and hamartoma risk in neurofibromatosis
More informationAssociation of Methylenetetrahydrofolate reductase (MTHFR 677C>T) polymorphisms with Ovarian Malignancy in women of Northern India
214 Association of Methylenetetrahydrofolate reductase (MTHFR 677C>T) polymorphisms with Ovarian Malignancy in women of Northern India Authors:, Rinki Kumari 1, Anamika Tiwari, Aruna Agrwal, G.P.I. Singh,
More informationZurich Open Repository and Archive. Long-term survival of glioblastoma patients treated with radiotherapy and lomustine plus temozolomide
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2009 Long-term survival of glioblastoma patients treated with radiotherapy and lomustine
More informationA meta-analysis of MTRR A66G polymorphism and colorectal cancer susceptibility
JBUON 2015; 20(3): 918-922 ISSN: 1107-0625, online ISSN: 2241-6293 www.jbuon.com E-mail: editorial_office@jbuon.com ORIGINAL ARTICLE A meta-analysis of MTRR A66G polymorphism and colorectal cancer susceptibility
More informationLipid Markers. Independent Risk Factors. Insulin Resistance Score by Lipid Fractionation
Patient: SAMPLE PATIENT DOB: Sex: MRN: 3701 CV Health Plus Genomics - Plasma, Serum & Buccal Swab Methodology: Chemiluminescent, Enzymatic, Immunoturbidimetric, NMR and PCR Lipid Markers Cholesterol LDL-
More informationTrans-HHS Workshop: Diet, DNA Methylation Processes and Health
Trans-HHS Workshop: Diet, DNA Methylation Processes and Health Nutritional and Genetic Inefficiencies in One-Carbon Metabolism and Cervical Cancer Risk 1 Regina G. Ziegler, 2 Stephanie J. Weinstein and
More informationGenetic testing for abnormalities in the MTHFR, MTR, MTRR, MMADHC and CBS genes has been proposed for several purposes:
Medical Policy Manual Topic: Genetic Testing for Methionine Metabolism Enzymes, including MTHFR, for Indications Other than Thrombophilia Date of Origin: January 2014 Section: Genetic Testing Last Reviewed
More informationThe influence of the number of haplotypes of MTHFR 1298A-677C alleles on the predicted probability to respond to methotrexate in early RA patients
Chapter 7 The influence of the number of haplotypes of MTHFR 1298A-677C alleles on the predicted probability to respond to methotrexate in early RA patients Wouter M. Kooloos 1, Judith A.M Wessels 1, S.M.
More informationANALYSIS OF IL17 AND IL17RA POLYMORPHISMS IN SPANISH PSORIASIS PATIENTS: ASSOCIATION WITH RISK FOR DISEASE.
ANALYSIS OF IL17 AND IL17RA POLYMORPHISMS IN SPANISH PSORIASIS PATIENTS: ASSOCIATION WITH RISK FOR DISEASE. Batalla A, Coto E*, González-Lara L, González- Fernández D, Maldonado-Seral C, García-García
More informationLack of association between ERCC5 gene polymorphisms and gastric cancer risk in a Chinese population
Lack of association between ERCC5 gene polymorphisms and gastric cancer risk in a Chinese population J.J. Lu, H.Q. Zhang, P. Mai, X. Ma, X. Chen, Y.X. Yang and L.P. Zhang Gansu Provincial Hospital, Donggang
More informationGenetic variability of genes involved in DNA repair influence treatment outcome in osteosarcoma
Genetic variability of genes involved in DNA repair influence treatment outcome in osteosarcoma M.J. Wang, Y. Zhu, X.J. Guo and Z.Z. Tian Department of Orthopaedics, Xinxiang Central Hospital, Xinxiang,
More informationLack of association between IL-6-174G>C polymorphism and lung cancer: a metaanalysis
Lack of association between IL-6-174G>C polymorphism and lung cancer: a metaanalysis Y. Liu, X.L. Song, G.L. Zhang, A.M. Peng, P.F. Fu, P. Li, M. Tan, X. Li, M. Li and C.H. Wang Department of Respiratory
More informationMyoglobin A79G polymorphism association with exercise-induced skeletal muscle damage
Myoglobin A79G polymorphism association with exercise-induced skeletal muscle damage T. Cui and M.S. Jiang College of Physical Education, Shandong University of Finance and Economics, Ji nan, Shandong,
More informationACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss
doi:10.1111/j.1447-0756.2008.00792.x J. Obstet. Gynaecol. Res. Vol. 34, No. 3: 301 306, June 2008 ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss Venkatesan Vettriselvi, Krishnaswami
More informationDisclosure. Dagan Wells University of Oxford Oxford, United Kingdom
Disclosure Dagan Wells University of Oxford Oxford, United Kingdom Disclosure Declared to be member of the advisory board, board of directors or other similar groups of Illumina Objectives Consider Aneuploidy
More informationMultistep nature of cancer development. Cancer genes
Multistep nature of cancer development Phenotypic progression loss of control over cell growth/death (neoplasm) invasiveness (carcinoma) distal spread (metastatic tumor) Genetic progression multiple genetic
More informationHigh-dose methotrexate toxicity in elderly patients with primary central nervous system lymphoma
Original article Annals of Oncology 16: 445 449, 2005 doi:10.1093/annonc/mdi075 Published online 14 January 2005 High-dose methotrexate toxicity in elderly patients with primary central nervous system
More informationSubmitted to Leukemia as a Letter to the Editor, May Male preponderance in chronic lymphocytic leukemia utilizing IGHV 1-69.
Submitted to Leukemia as a Letter to the Editor, May 2007 To the Editor, Leukemia :- Male preponderance in chronic lymphocytic leukemia utilizing IGHV 1-69. Gender plays an important role in the incidence,
More informationA growing body of evidence has highlighted the role of
454 LETTER TO JMG 5,10-methylenetetrahydrofolate reductase (MTHFR) 677CRT and 1298ARC mutations are associated with DNA hypomethylation R Castro, I Rivera, P Ravasco, M E Camilo, C Jakobs, H J Blom, I
More informationHigh Blood Pressure in Irish Adults
High Blood Pressure in Irish Adults Preliminary findings and lessons learned from two JINGO cohorts Helene McNulty Northern Ireland Centre for Food and Health (NICHE) University of Ulster Mortality due
More informationMaternal Vitamin Use, Genetic Variation of Infant Methylenetetrahydrofolate Reductase, and Risk for Spina Bifida
American Journal of Epidemiology Copyright 1998 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved Vol. 18,. 1 Printed in U.S.A. Maternal Vitamin Use, Genetic Variation
More informationThe C677T Mutation in the Methylenetetrahydrofolate Reductase Gene
ARTHRITIS & RHEUMATISM Vol. 44, No. 11, November 2001, pp 2525 2530 2001, American College of Rheumatology Published by Wiley-Liss, Inc. The C677T Mutation in the Methylenetetrahydrofolate Reductase Gene
More informationInfluence of interleukin-18 gene polymorphisms on acute pancreatitis susceptibility in a Chinese population
Influence of interleukin-18 gene polymorphisms on acute pancreatitis susceptibility in a Chinese population H.B. Gui 1, X.G. Du 2, Z.H. Fu 3 and X.M. Chen 1 1 Department of Emergency, The First Affiliated
More informationZurich Open Repository and Archive. Long-term survival of glioblastoma patients treated with radiotherapy and lomustine plus temozolomide
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 19 CH-857 Zurich http://www.zora.uzh.ch Year: 29 Long-term survival of glioblastoma patients treated with radiotherapy and lomustine
More informationPrognostic Significance of the Polymorphisms in Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene in Lung Cancer
Prognostic Significance of the Polymorphisms in Thymidylate Synthase and Methylenetetrahydrofolate Reductase Gene in Lung Cancer AKIRA TAKEHARA, KAZUYUKI KAWAKAMI, NAOHIRO OHTA, KAEKO OYAMA, YASUHIKO OTA,
More informationNo Association Between MTHFR A1298C and MTRR A66G Polymorphisms, and MS in an Australian Cohort
No Association Between MTHFR A1298C and MTRR A66G Polymorphisms, and MS in an Australian Cohort A.L. Szvetko a, J. Fowdar a, J. Nelson a, N. Colson a, L. Tajouri a, P.A. Csurhes b, M.P. Pender b, c and
More informationUniversity of Zurich. Temozolomide and MGMT forever? Zurich Open Repository and Archive. Weller, M. Year: 2010
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich Year: 2010 Temozolomide and MGMT forever? Weller, M Weller, M (2010). Temozolomide and MGMT forever? Neuro-Oncology,
More informationAdvanced Methylation Detoxification Profile
Page: 1 of 6 Pages Methylation Detoxification Cycle: One or more mutations present: Enzyme activity will be mildly to moderately reduced (see detailed report)* No mutations present: Normal enzyme activity*
More informationA. Orsini 1, I. Sammartino 1, A. Valetto 2, V. Bertini 2, P. Marchese 1*, A. Bonuccelli 1 and D. G. Peroni 1
Orsini et al. Italian Journal of Pediatrics (2018) 44:106 https://doi.org/10.1186/s13052-018-0546-1 RESEARCH Methylenetetrahydrofolate reductase polymorphism (MTHFR C677T) and headache in children: a retrospective
More informationMethylenetetrahydrofolate Reductase Polymorphisms and Homocysteine-Lowering Effect of Vitamin Therapy in Singaporean Stroke Patients
Methylenetetrahydrofolate Reductase Polymorphisms and Homocysteine-Lowering Effect of Vitamin Therapy in Singaporean Stroke Patients Grace Y.-H. Ho, BSc (Hons); John W. Eikelboom, FRCPA; Graeme J. Hankey,
More informationASSOCIATION BETWEEN MTHFR (C677T) GENE POLYMORPHISM WITH BREAST CANCER IN NORTHERN IRAN
WCRJ 2017; 4 (2): e876 ASSOCIATION BETWEEN MTHFR (C677T) GENE POLYMORPHISM WITH BREAST CANCER IN NORTHERN IRAN A. HEDAYATIZADEH-OMRAN, R. ALIZADEH-NAVAEI, F. TOGHANI-HULARI, O. AMJADI Gastrointestinal
More informationInvestigating the role of polymorphisms in mir-146a, -149, and -196a2 in the development of gastric cancer
Investigating the role of polymorphisms in mir-146a, -149, and -196a2 in the development of gastric cancer Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong
More informationSeptember 20, Submitted electronically to: Cc: To Whom It May Concern:
History Study (NOT-HL-12-147), p. 1 September 20, 2012 Re: Request for Information (RFI): Building a National Resource to Study Myelodysplastic Syndromes (MDS) The MDS Cohort Natural History Study (NOT-HL-12-147).
More informationLack of Association between Endoplasmic Reticulum Stress Response Genes and Suicidal Victims
Kobe J. Med. Sci., Vol. 53, No. 4, pp. 151-155, 2007 Lack of Association between Endoplasmic Reticulum Stress Response Genes and Suicidal Victims KAORU SAKURAI 1, NAOKI NISHIGUCHI 2, OSAMU SHIRAKAWA 2,
More information2015 EUROPEAN CANCER CONGRESS
2015 EUROPEAN CANCER CONGRESS 25-29 September 2015 Vienna, Austria SUMMARY The European Cancer Congress (ECC 2015) combined the 40th European Society for Medical Oncology (ESMO) congress with the 18th
More informationPolymorphism of the PAI-1gene (4G/5G) may be linked with Polycystic Ovary Syndrome and associated pregnancy disorders in South Indian Women
www.bioinformation.net Volume 13(5) Hypothesis Polymorphism of the PAI-1gene (4G/5G) may be linked with Polycystic Ovary Syndrome and associated pregnancy disorders in South Indian Women Maniraja Jesintha
More informationZurich Open Repository and Archive. Procarbazine and CCNU as initial treatment in gliomatosis cerebri
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2008 Procarbazine and CCNU as initial treatment in gliomatosis cerebri Glas, M;
More informationPolicy for Central Nervous System [CNS] Prophylaxis in Lymphoid Malignancies
Policy for Central Nervous System [CNS] Prophylaxis in Lymphoid Malignancies UNCONTROLLED WHEN PRINTED Note: NOSCAN Haematology MCN has approved the information contained within this document to guide
More informationVIRUSES AND CANCER Michael Lea
VIRUSES AND CANCER 2010 Michael Lea VIRAL ONCOLOGY - LECTURE OUTLINE 1. Historical Review 2. Viruses Associated with Cancer 3. RNA Tumor Viruses 4. DNA Tumor Viruses HISTORICAL REVIEW Historical Review
More informationJ.W. Muntjewerff, Homocysteine metabolism and risk of schizophrenia. Chapter 9. Summary, Discussion and Future perspectives
Chapter 9 Summary, Discussion and Future perspectives 87 Summary A general introduction on homocysteine metabolism, and clinical implications of hyperhomocysteinemia along with epidemiological evidence
More informationRetrospective Genetic Analysis of Efficacy and Adverse Events in a Rheumatoid Arthritis Population Treated with Methotrexate and Anti-TNF-α
Retrospective Genetic Analysis of Efficacy and Adverse Events in a Rheumatoid Arthritis Population Treated with Methotrexate and Anti-TNF-α Foti A 1, Lichter D 1, Shadick NA 2, Maher NE 2, Ginsburg GS
More informationHomocysteine and its Catabolism UNDERSTANDING THE METHYLATION PATHWAY
Homocysteine and its Catabolism UNDERSTANDING THE METHYLATION PATHWAY Objectives Undearstand the basics of methylation Learn the three disposal routes of homocysteine catabolism Understand the clinical
More informationCYP19 gene polymorphisms and the susceptibility to breast cancer in Xinjiang Uigur women
CYP19 gene polymorphisms and the susceptibility to breast cancer in Xinjiang Uigur women L. Yang, X.Y. Wang, Y.T. Li, H.L. Wang, T. Wu, B. Wang, Q. Zhao, D. Jinsihan and L.P. Zhu The Department of Mammary
More informationMTHFR C677T polymorphism and osteoporotic fracture in postmenopausal women: a meta-analysis
MTHFR C677T polymorphism and osteoporotic fracture in postmenopausal women: a meta-analysis J.Z. Guan, M. Wu, Y.Z. Xiao, J.S. Zhou and Z.D. Wang Anhui Key Laboratory of Tissue Transplantation, Institute
More informationChapter 4 INSIG2 Polymorphism and BMI in Indian Population
Chapter 4 INSIG2 Polymorphism and BMI in Indian Population 4.1 INTRODUCTION Diseases like cardiovascular disorders (CVD) are emerging as major causes of death in India (Ghaffar A et. al., 2004). Various
More informationGenetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia
Cancer Causes Control (2011) 22:1243 1258 DOI 10.1007/s10552-011-9795-7 ORIGINAL PAPER Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia Catherine Metayer Ghislaine
More informationMethylene Tetrahydrofolate Reductase Deficiency: Practical Impact on Pediatric Medical and Dental Practice. Prepared by
Running head: METHYLENE TETRAHYDROFOLATE REDUCTASE DEFICIENCY 1 Methylene Tetrahydrofolate Reductase Deficiency: Practical Impact on Pediatric Medical and Dental Practice Prepared by Darleen Claire Wodzenski,
More informationLack of association of IL-2RA and IL-2RB polymorphisms with rheumatoid arthritis in a Han Chinese population
Lack of association of IL-2RA and IL-2RB polymorphisms with rheumatoid arthritis in a Han Chinese population J. Zhu 1 *, F. He 2 *, D.D. Zhang 2 *, J.Y. Yang 2, J. Cheng 1, R. Wu 1, B. Gong 2, X.Q. Liu
More information5,10-Methylenetetrahydrofolate Reductase (MTHFR) 1298
: 30 4 2003 Kor. J. Fertil. Steril., Vol. 30, No. 4, 2003, 12 5,10-Methylenetetrahydrofolate Reductase (MTHFR) 1298 1, 2 3, 1 2 2 1 1 3 3 3 1 Genetic analysis for Polymorphism of 5, 10-Methylenetetrahydrofolate
More informationMethylene Tetrahydrofolate Reductase Gene and Coronary Artery Disease
Methylene Tetrahydrofolate Reductase Gene and Coronary Artery Disease M. P. Iqbal,P. M. Frossard ( Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi. ) Hyperhomocysteinemia
More informationCorrelations between the COMT gene rs4680 polymorphism and susceptibility to ovarian cancer
Correlations between the COMT gene rs4680 polymorphism and susceptibility to ovarian cancer W. Pan 1 and H. Liao 2 1 Department of Obstetrics and Gynecology, Huangshi Central Hospital of Hubei Province
More informationThe effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment outcome in rheumatoid arthritis
Brazilian Journal of Medical and Biological Research (2009) 42: 660-664 ISSN 0100-879X The effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment outcome in rheumatoid arthritis A.
More informationPolymorphisms of 5,10-methylenetetrahydrofolate reductase and thymidylate synthase,
Polymorphisms of,-methylenetetrahydrofolate reductase and thymidylate synthase, dietary folate intake, and the risk of leukemia in adults Ping Liu 1, Min Zhang 1,, Xing Xie, Jie Jin, and C D Arcy J Holman
More informationMultiple Fibroadenomas Harboring Carcinoma in Situ in a Woman with a Familty History of Breast/ Ovarian Cancer
Multiple Fibroadenomas Harboring Carcinoma in Situ in a Woman with a Familty History of Breast/ Ovarian Cancer A Kuijper SS Preisler-Adams FD Rahusen JJP Gille E van der Wall PJ van Diest J Clin Pathol
More informationImpact of FPGS and GGH SNPs on Plasma Folate and Homocysteine Levels in the Singapore Chinese Health Study
Impact of FPGS and GGH SNPs on Plasma Folate and Homocysteine Levels in the Singapore Chinese Health Study A THESIS SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY Sarah
More informationMOLECULAR MEDICINE REPORTS 8: , 2013
MOLECULAR MEDICINE REPORTS 8: 919-927, 2013 Association between MTHFR C677T, MTHFR A1298C and MS A2756G polymorphisms and risk of cervical intraepithelial neoplasia II/III and cervical cancer: A meta-analysis
More informationTHE ROLE OF B-VITAMINS GENE INTERACTIONS IN COLORECTAL CARCINOGENESIS A MOLECULAR EPIDEMIOLOGICAL APPROACH
THE ROLE OF B-VITAMINS GENE INTERACTIONS IN COLORECTAL CARCINOGENESIS A MOLECULAR EPIDEMIOLOGICAL APPROACH Promotor Prof. dr. ir. F.J. Kok Hoogleraar Voeding en Gezondheid Wageningen Universiteit Co-promotoren
More informationPharmacogenetics in: Primary Care. Bradley T. Wajda D.O.
Pharmacogenetics in: Primary Care Bradley T. Wajda D.O. Pharmacogenomics Defined Pharmacogenomics uses information about a person s genetic makeup, or genome, to choose the drugs and drug doses that are
More informationPolymorphisms of DNA repair-related genes with susceptibility and prognosis of prostate cancer
Polymorphisms of DNA repair-related genes with susceptibility and prognosis of prostate cancer X.J. Zhang, P. Liu and F. Zhu Urology Department, The First Affiliated Hospital of Xinxiang Medical University,
More informationBio 100 Guide 08.
Bio 100 Guide 08 http://images.andrewsmcmeel.com/media/3820/medium.jpg http://www.biology.iupui.edu/biocourses/n100/images/11nondisjunction.gif http://www.unm.edu/~vscience/images/hela%20karyotype%203%20(1000x).jpg
More informationAssociation between matrix metalloproteinase-9 rs polymorphism and development of coronary artery disease in a Chinese population
Association between matrix metalloproteinase-9 rs3918242 polymorphism and development of coronary artery disease in a Chinese population L.M. Qin 1, G.M. Qin 2, X.H. Shi 1, A.L. Wang 1 and H. Zuo 1 1 The
More informationRELATIONSHIP OF HOMOCYSTEINE AND ITS METABOLIC ENZYME GENES POLYMORPHISMS WITH ESSENTIAL HYPERTENSION IN MONGOLIANS
377 A 010050 Hcy 165 150 - PCR-RFLP MS A 2756 G Hcy Hcy Hcy P0.05 MS A 2756 G Hcy R544.1 A DOI:10.16343/j.cnki.issn.2095-512x.2016.05.001 2095-512X 2016 05-0377-05 RELATIONSHIP OF HOMOCYSTEINE
More informationConditions. Name : dummy Age/sex : xx Y /x. Lab No : xxxxxxxxx. Rep Centre : xxxxxxxxxxx Ref by : Dr. xxxxxxxxxx
Name : dummy Age/sex : xx Y /x Lab No : xxxxxxxxx Rep Centre : xxxxxxxxxxx Ref by : Dr. xxxxxxxxxx Rec. Date : xx/xx/xx Rep Date : xx/xx/xx GENETIC MAPPING FOR ONCOLOGY Conditions Melanoma Prostate Cancer
More informationLymphoma: What You Need to Know. Richard van der Jagt MD, FRCPC
Lymphoma: What You Need to Know Richard van der Jagt MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing
More informationAllelic and Haplotype Frequencies of the p53 Polymorphisms in Brain Tumor Patients
Physiol. Res. 51: 59-64, 2002 Allelic and Haplotype Frequencies of the p53 Polymorphisms in Brain Tumor Patients E. BIROŠ, I. KALINA, A. KOHÚT 1, E. BOGYIOVÁ 2, J. ŠALAGOVIČ, I. ŠULLA 3 Department of Medical
More informationPolymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia
NEOPLASIA Polymorphisms in the thymidylate synthase and serine hydroxymethyltransferase genes and risk of adult acute lymphocytic leukemia Christine F. Skibola, Martyn T. Smith, Alan Hubbard, Barry Shane,
More informationGenetic variation in folate metabolism is associated with the risk of conotruncal heart defects in a Chinese population
Wang et al. BMC Pediatrics (2018) 18:287 https://doi.org/10.1186/s12887-018-1266-9 RESEARCH ARTICLE Genetic variation in folate metabolism is associated with the risk of conotruncal heart defects in a
More informationSLE AND CANCER: DOUBLE TROUBLE. Sasha Bernatsky MD FRCPC PhD McGill University Health Centre
SLE AND CANCER: DOUBLE TROUBLE Sasha Bernatsky MD FRCPC PhD McGill University Health Centre DISCLOSURES: NONE ACKNOWLEDGEMENTS Ann Clarke Calgary, Alberta Rosalind Ramsey-Goldman Northwestern University
More informationRESEARCH COMMUNICATION. Mutational Analysis of the MTHFR Gene in Breast Cancer Patients of Pakistani Population
RESEARCH COMMUNICATION Mutational Analysis of the MTHFR Gene in Breast Cancer Patients of Pakistani Population Muhammad Akram, FA Malik, Mahmood Akhtar Kayani* Abstract Objectives: Since methylenetetrahydrofolate
More informationMTHFR gene polymorphism, homocysteine and cardiovascular disease
Public Health Nutrition: 4(2B), 493±497 DOI: 10.1079/PHN2001159 MTHFR gene polymorphism, homocysteine and cardiovascular disease Claudio Cortese 1 * and Corradino Motti 2 1 Department of Internal Medicine,
More information