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Sjöström, Sara
Publications (9 of 9) Show all publications
Wibom, C., Sjöström, S., Henriksson, R., Brännström, T., Broholm, H., Rydén, P., . . . Melin, B. S. (2012). DNA-repair gene variants are associated with glioblastoma survival. Acta Oncologica, 51(3), 325-332
Open this publication in new window or tab >>DNA-repair gene variants are associated with glioblastoma survival
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2012 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 3, p. 325-332Article in journal (Refereed) Published
Abstract [en]

Patient outcome from glioma may be influenced by germline variation. Considering the importance of DNA repair in cancer biology as well as in response to treatment, we studied the relationship between 1458 SNPs, which captured the majority of the common genetic variation in 136 DNA repair genes, in 138 glioblastoma samples from Sweden and Denmark. We confirmed our findings in an independent cohort of 121 glioblastoma patients from the UK. Our analysis revealed nine SNPs annotating MSH2, RAD51L1 and RECQL4 that were significantly (p < 0.05) associated with glioblastoma survival.

Place, publisher, year, edition, pages
Informa Healthcare, 2012
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-48594 (URN)10.3109/0284186X.2011.616284 (DOI)000302731800007 ()22017238 (PubMedID)2-s2.0-84859753765 (Scopus ID)
Available from: 2011-10-25 Created: 2011-10-25 Last updated: 2023-03-24Bibliographically approved
Sjöström, S., Ghasimi, S., Broholm, H., Brannstrom, T., Johansen, C., Collatz-Laier, H., . . . Melin, B. (2012). EGFR expression and glioblastoma outcome. Paper presented at 10th Congress of the European-Association-of-NeuroOncology, SEP 06-09, 2012, Marseille, FRANCE. Neuro-Oncology, 14(Suppl. 3), 19-19
Open this publication in new window or tab >>EGFR expression and glioblastoma outcome
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2012 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 14, no Suppl. 3, p. 19-19Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford: Oxford University Press, 2012
National Category
Cancer and Oncology Neurosciences
Identifiers
urn:nbn:se:umu:diva-60322 (URN)000308545600070 ()
Conference
10th Congress of the European-Association-of-NeuroOncology, SEP 06-09, 2012, Marseille, FRANCE
Available from: 2012-11-09 Created: 2012-10-09 Last updated: 2018-06-08Bibliographically approved
Sjöström, S. (2012). Risk and prognostic factors for malignant glioma. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Risk and prognostic factors for malignant glioma
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Glioblastoma is the most common and aggressive type of glioma and associated with poor prognosis. Apart from ionizing radiation and some rare genetic disorders, few aetiological factors have been identified for primary brain tumours. Inverse associations to asthma and low IgG levels for varicella zoster virus have in previous studies indicated that the immune system may play a role in glioma development. Little is known about prognostic factors in glioma. Previous studies have shown an association between age, Karnofsky performance status, O6-methylguanine-DNA methyltransferase (MGMT) hypermethylation, and prognosis. Polymorphisms in different low penetrance genes have in some studies been associated with glioma prognosis.

Material and methods: In paper I, we analysed IgG levels for four different viruses, Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella zoster virus (VZV) and adenovirus (Ad), in prediagnostic blood samples from 197 cases with glioma and 394 controls collected from three large cohorts: the Northern Sweden Health and Disease Study; the Malmö Diet and Cancer Study; and the Diet, Cancer and Health cohort from Copenhagen. ELISA was used to measure IgG levels and for EBV response to both the nuclear antigen (EBNA1) and the viral capsid antigen (VCA) was measured, for VCA using immunoflourescence. IgG levels were divided into quartiles and binary logistic regression was used to compare the quartiles in cases and controls. All odds ratios were adjusted for age, sex, and cohort. In paper II-IV, we studied 176 glioblastoma cases from Sweden and Denmark. We collected treatment and follow-up data on the cases. We genotyped 30 tagging SNPs in EGF, 89 in EGFR, 27 in VEGFR2, and 17 in VEGF. We also studied 1458 SNPs in 136 DNA repair genes. Hazard ratios were calculated using Cox regression; the major allele was set as categorical variable and all HR were adjusted for age, sex, country, and treatment. For the DNA repair gene results, we adjusted the p-values for multiple testing. Significant findings were confirmed in separate datasets.

Results and Discussion: We found a trend towards higher IgG VZV levels in controls compared to glioma cases, especially when restricting the analyses to only include glioma cases with at least 2 years between blood sample and diagnosis. This finding might indicate that there is an aetiological and not a disease-related association. This confirms previous findings and support that a strong immune system can detect and inhibit growth of small cancer clusters. In EGF, we found seven SNPs in one haplotype block that were significantly associated with glioblastoma survival. Four of the SNPs were available for confirmation; however, none reached statistical significance. One explanation could be age differences in the different cohorts. In EGFR, four SNPs associated with survival were found; however, as 89 polymorphisms were tested this was the expected outcome by chance. In VEGF and VEGFR2, we found two SNPs associated with glioblastoma survival, but they could not be confirmed in the separate dataset, and due to multiple testing, were considered to be false positives. Among the DNA repair genes, we found nine SNPs in three genes-MSH2, RAD51L1 and RECQL4-associated with glioblastoma survival after confirmation and adjustment for age, sex, country, and treatment. After adjusting for multiple testing, one SNP in MSH2 and one in RECQL4 remained significant.

Conclusions: Our studies provide additional knowledge to the aetiological and prognostic factors important for glioma, emphasising the possible importance of immune function mechanisms. We found limited evidence for the role of genetic variants in glioma progression genes, and some for DNA repair variants as prognostic factors for glioblastoma survival.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2012. p. 67
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1536
Keywords
Glioma, Glioblastoma, Risk, Outcome, EGR, EGFR, VEGF, VEGFR, DNA repair, virus
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-61905 (URN)978-91-7459-521-5 (ISBN)
Public defence
2012-12-21, Sal E04, by 6 E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2012-11-30 Created: 2012-11-29 Last updated: 2018-06-08Bibliographically approved
Berntsson, S. G., Wibom, C., Sjöström, S., Henriksson, R., Brännström, T., Broholm, H., . . . Melin, B. S. (2011). Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas. Journal of Neuro-Oncology, 105(3), 531-538
Open this publication in new window or tab >>Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas
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2011 (English)In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 105, no 3, p. 531-538Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054-0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.

Keywords
Gliomas WHO grade II/III, DNA repair, ERCC6, Outcome, Polymorphism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-47496 (URN)10.1007/s11060-011-0614-5 (DOI)21643987 (PubMedID)2-s2.0-82955203690 (Scopus ID)
Available from: 2011-09-22 Created: 2011-09-22 Last updated: 2023-03-23Bibliographically approved
Sjöström, S., Wibom, C., Andersson, U., Brännstrom, T., Broholm, H., Johansen, C., . . . Melin, B. (2011). Genetic variations in VEGF and VEGFR2 and glioblastoma outcome. Journal of Neuro-Oncology, 104(2), 523-527
Open this publication in new window or tab >>Genetic variations in VEGF and VEGFR2 and glioblastoma outcome
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2011 (English)In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 104, no 2, p. 523-527Article in journal (Refereed) Published
Abstract [en]

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs significantly associated to survival, namely rs2071559 and rs12502008. However, these results are likely to be false positives due to multiple testing and could not be confirmed in a separate dataset. Overall, this study provides little evidence that VEGF and VEGFR2 polymorphisms are important for glioblastoma survival.

Place, publisher, year, edition, pages
Boston: Nijhoff, 2011
Keywords
Vascular endothelial growth factor (VEGF); Vascular endothelial growth factor receptor (VEGFR); Glioblastoma outcome; Association study; Survival
National Category
Cancer and Oncology Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-47393 (URN)10.1007/s11060-010-0504-2 (DOI)2-s2.0-80052615267 (Scopus ID)
Available from: 2011-09-23 Created: 2011-09-20 Last updated: 2023-03-24Bibliographically approved
Sjöström, S., Hjalmars, U., Juto, P., Wadell, G., Hallmans, G., Tjönneland, A., . . . Melin, B. S. (2011). Human immunoglobulin G levels of viruses and associated glioma risk. Cancer Causes and Control, 22(9), 1259-1266
Open this publication in new window or tab >>Human immunoglobulin G levels of viruses and associated glioma risk
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2011 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 22, no 9, p. 1259-1266Article in journal (Refereed) Published
Abstract [en]

Few consistent etiological factors have been identified for primary brain tumors. Inverse associations to asthma and low levels of varicella-zoster virus, immunoglobulin (Ig) levels in prevalent cases have indicted a role for the immune system in the development of glioma. Because samples from prevalent cases of glioma could be influenced by treatments such as steroids and chemotherapy, we investigated pre-diagnostic samples from three large Scandinavian cohorts. To test the hypothesis that immune response levels to these viruses are associated etiologically with glioma risk, we investigated pre-diagnostic immunoglobulin levels for cytomegalovirus (CMV), varicella-zoster virus (VZV), adenovirus (Ad), and Epstein-Barr virus (EBV) including the nuclear antigen (EBNA1) using plasma samples from 197 cases of adult glioma and 394 controls collected from population-based cohorts in Sweden and Denmark. Low VZV IgG levels were marginally significantly more common in glioma cases than the controls (odds ratio (OR) = 0.68, 95% CI 0.41-1.13) for the fourth compared with the first quartile (p = 0.06 for trend). These results were more prominent when analyzing cases with blood sampling at least 2 years before diagnosis (OR = 0.63, 95% CI 0.37-1.08) (p = 0.03). No association with glioma risk was observed for CMV, EBV, and adenovirus.

Place, publisher, year, edition, pages
Springer, 2011
Keywords
Glioma, Glioblastoma, Immunoglobulin G, Virus, Case–control study
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-45928 (URN)10.1007/s10552-011-9799-3 (DOI)21717196 (PubMedID)2-s2.0-80052306232 (Scopus ID)
Available from: 2011-08-22 Created: 2011-08-22 Last updated: 2023-03-24Bibliographically approved
Andersson, U., Schwartzbaum, J., Wiklund, F., Sjöström, S., Liu, Y., Tsavachidis, S., . . . Melin, B. (2010). A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk. Acta Oncologica, 49(6), 767-775
Open this publication in new window or tab >>A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
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2010 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 6, p. 767-775Article in journal (Refereed) Published
Abstract [en]

Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.

Place, publisher, year, edition, pages
Informa Healthcare, 2010
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-35334 (URN)10.3109/0284186X.2010.480980 (DOI)000280591800003 ()20446891 (PubMedID)
Available from: 2010-08-13 Created: 2010-08-13 Last updated: 2018-06-08Bibliographically approved
Sjöström, S., Andersson, U., Liu, Y., Brännström, T., Broholm, H., Johansen, C., . . . Melin, B. (2010). Genetic variations in EGF and EGFR and glioblastoma outcome. Neuro-Oncology, 12(8), 815-821
Open this publication in new window or tab >>Genetic variations in EGF and EGFR and glioblastoma outcome
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2010 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 12, no 8, p. 815-821Article in journal (Refereed) Published
Abstract [en]

Few prognostic factors have been associated with glioblastoma survival. We analyzed a complete tagging of the epidermal growth factor (EGF) and EGF receptor (EGFR) gene polymorphisms as potential prognostic factors. Thirty tagging single-nucleotide polymorphisms (SNPs) in EGF and 89 tagging SNPs in EGFR were analyzed for association with survival in 176 glioblastoma cases. Validation analyses were performed for 4 SNPs in a set of 638 glioblastoma patients recruited at The University of Texas M. D. Anderson Cancer Center (MDACC). Three hundred and seventy-four glioblastoma patients aged 50 years or older at diagnosis were subanalyzed to enrich for de novo arising glioblastoma. We found 7 SNPs in haplotype 4 in EGF that were associated with prognosis in glioblastoma patients. In EGFR, 4 of 89 SNPs were significantly associated with prognosis but judged as false positives. Four of the significantly associated EGF polymorphisms in haplotype block 4 were validated in a set from MDACC; however, none of the associations were clearly replicated. rs379644 had a hazard ratio (HR) of 1.19 (0.94-1.51) in the whole population with 18.6 months survival in the risk genotype compared with 24.5 in the reference category. As the median age differed slightly between the 2 study sets, the MDACC cases aged 50 or older at diagnosis were analyzed separately (rs379644, HR 1.32 [0.99-1.78]), which is marginally significant and partially validates our findings. This study is, to our knowledge, the first to perform a comprehensive tagging of the EGF and EGFR genes, and the data give some support that EGF polymorphisms might be associated with poor prognosis. Further confirmation in independent data sets of prospective studies is necessary to establish EGF as prognostic risk factor.

Keywords
EGF, EGFR, glioblastoma, outcome, polymorphism
National Category
Cancer and Oncology
Research subject
Oncology; Pathology
Identifiers
urn:nbn:se:umu:diva-35335 (URN)10.1093/neuonc/noq018 (DOI)000280705800007 ()20197289 (PubMedID)2-s2.0-78149473041 (Scopus ID)
Available from: 2010-08-13 Created: 2010-08-13 Last updated: 2023-03-24Bibliographically approved
Andersson, U., Osterman, P., Sjöström, S., Johansen, C., Henriksson, R., Brännström, T., . . . Malmer, B. (2009). MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome.. International journal of cancer. Journal international du cancer, 125(4), 968-972
Open this publication in new window or tab >>MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome.
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2009 (English)In: International journal of cancer. Journal international du cancer, ISSN 1097-0215, Vol. 125, no 4, p. 968-972Article in journal (Refereed) Published
Abstract [en]

The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival was analysed using Kaplan-Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype was not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus the LL was nonsignificantly increased HR 1.46 (0.81-2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR was 2.10 (1.41-3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations.

Identifiers
urn:nbn:se:umu:diva-24344 (URN)10.1002/ijc.24363 (DOI)19405125 (PubMedID)2-s2.0-67650073372 (Scopus ID)
Available from: 2009-06-30 Created: 2009-06-30 Last updated: 2023-03-24
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