umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Löfgren Burström, Anna
Alternative names
Publications (10 of 15) Show all publications
Myte, R., Gylling, B., Häggström, J., Häggström, C., Zingmark, C., Löfgren Burström, A., . . . van Guelpen, B. (2019). Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status. International Journal of Cancer, 145(2), 327-337
Open this publication in new window or tab >>Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status
Show others...
2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 2, p. 327-337Article in journal (Refereed) Published
Abstract [en]

Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population-based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow-up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all pheterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
BRAF, KRAS, colorectal cancer, metabolic factors, microsatellite instability, risk factors
National Category
Cancer and Oncology Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-158782 (URN)10.1002/ijc.32104 (DOI)30613980 (PubMedID)2-s2.0-85060622510 (Scopus ID)
Note

Originally included in thesis in manuscript form with title [Metabolic factors and colorectal cancer risk by KRAS and BRAF mutation status]

Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-06-11Bibliographically approved
Lundberg, I., Wikberg, M. L., Ljuslinder, I., Li, X., Myte, R., Zingmark, C., . . . Palmqvist, R. (2018). MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers. Anticancer Research, 38(2), 677-683
Open this publication in new window or tab >>MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers
Show others...
2018 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 38, no 2, p. 677-683Article in journal (Refereed) Published
Abstract [en]

Background/Aim: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS-and BRAF-mutated CRCs.

Materials and Methods: Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.

Results: Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.

Conclusion: Our results suggest that KRAS and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS-and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2018
Keywords
colorectal cancer, miRNA, KRAS, BRAF, molecular subgroups
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-133409 (URN)10.21873/anticanres.12272 (DOI)000423315300010 ()29374690 (PubMedID)
Note

Originally included in thesis in manuscript form

Available from: 2017-04-10 Created: 2017-04-10 Last updated: 2018-06-09Bibliographically approved
Myte, R., Gylling, B., Häggström, J., Schneede, J., Löfgren-Burström, A., Huyghe, J. R., . . . Van Guelpen, B. (2018). One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status. PLoS ONE, 13(4), Article ID e0196233.
Open this publication in new window or tab >>One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status
Show others...
2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196233Article in journal (Refereed) Published
Abstract [en]

Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147822 (URN)10.1371/journal.pone.0196233 (DOI)000430802400077 ()29694444 (PubMedID)
Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2019-05-24Bibliographically approved
Eklöf, V., Löfgren-Burström, A., Zingmark, C., Edin, S., Larsson, P., Karling, P., . . . Palmqvist, R. (2017). Cancer-associated fecal microbial markers in colorectal cancer detection. International Journal of Cancer, 141(12), 2528-2536
Open this publication in new window or tab >>Cancer-associated fecal microbial markers in colorectal cancer detection
Show others...
2017 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 12, p. 2528-2536Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
F. nucleatum, clbA, colorectal cancer, gut microbiota, screening, stool
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142380 (URN)10.1002/ijc.31011 (DOI)000413549900019 ()28833079 (PubMedID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2019-01-02Bibliographically approved
Strömberg, N., Esberg, A., Sheng, N., Mårell, L., Löfgren-Burström, A., Danielsson, K. & Källestål, C. (2017). Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2. EBioMedicine, 26, 38-46
Open this publication in new window or tab >>Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2
Show others...
2017 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 26, p. 38-46Article in journal (Refereed) Published
Abstract [en]

Dental caries is a chronic infectious disease that affects billions of people with large individual differences in activity. We investigated whether PRH1 and PRH2 polymorphisms in saliva acidic proline-rich protein (PRP) receptors for indigenous bacteria match and predict individual differences in the development of caries. PRH1 and PRH2 variation and adhesion of indigenous and cariogenic (Streptococcus mutans) model bacteria were measured in 452 12-year-old Swedish children along with traditional risk factors and related to caries at baseline and after 5-years. The children grouped into low-to-moderate and high susceptibility phenotypes for caries based on allelic PRH1, PRH2 variation. The low-to-moderate susceptibility children (P1 and P4a-) experienced caries from eating sugar or bad oral hygiene or infection by S. mutans. The high susceptibility P4a (Db, PIF, PRP12) children had more caries despite receiving extra prevention and irrespective of eating sugar or bad oral hygiene or S. mutans-infection. They instead developed 3.9-fold more caries than P1 children from plaque accumulation in general when treated with orthodontic multibrackets; and had basic PRP polymorphisms and low DMBT1-mediated S. mutans adhesion as additional susceptibility traits. The present findings thus suggest genetic autoimmune-like (P4a) and traditional life style (P1) caries, providing a rationale for individualized oral care.

Keywords
Acidic proline-rich proteins, Chronic infections, Dental caries, Host susceptibility, PRH1, PRH2
National Category
Dentistry
Identifiers
urn:nbn:se:umu:diva-143131 (URN)10.1016/j.ebiom.2017.11.019 (DOI)29191562 (PubMedID)
Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2018-06-09Bibliographically approved
Ling, A., Löfgren-Burström, A., Larsson, P., Li, X., Wikberg, M. L., Öberg, Å., . . . Palmqvist, R. (2017). TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer. Oncoimmunology, 6(11), Article ID e1356143.
Open this publication in new window or tab >>TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer
Show others...
2017 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 6, no 11, article id e1356143Article in journal (Refereed) Published
Abstract [en]

The anti-tumor immune response has been shown to be of great prognostic importance in colorectal cancer (CRC) and so has the tumors ability for immune evasion. Our aim of this study was to investigate tumor factors that influence immunity. We used a gene expression array to search for potential mechanisms of tumor immune escape. One candidate gene identified was TAP1, involved in antigen presentation by MHC class I. TAP1 protein expression was evaluated by immunohistochemistry in 436 CRC patients of the Colorectal Cancer in Umeå Study cohort. We found a significant association between a downregulated expression of TAP1 and low infiltration of various subtypes of lymphocytes as well as macrophages. A downregulated expression of TAP1 was further found to be independent of molecular characteristics, suggesting TAP1 down-regulation to reach beyond the well described highly immunogenic MSI CRCs. A low expression of TAP1 was also significantly associated with poor prognosis in patients with CRC, a result that stayed significant in tumor front of early stage tumors (stage I-II) through multivariable analyses. Furthermore, we found that TAP1 expression was inversely correlated with methylation at sites in close proximity to the promoter region. In summary, our results show down-regulation of TAP1 to be a general mechanism of tumor immune escape in CRC and a poor prognostic factor in stage I-II CRC patients. We also suggest that methylation of the TAP1 gene may be a putative mechanism for TAP1 downregulation.

Keywords
TAP1, antigen presentation, colorectal cancer, immune escape, prognosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142377 (URN)10.1080/2162402X.2017.1356143 (DOI)000414522400004 ()29147604 (PubMedID)
Funder
Swedish Cancer Society, CAN 2014/858Västerbotten County Council, VLL-463871
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2018-11-13Bibliographically approved
Lundberg, I. V., Löfgren Burström, A., Edin, S., Eklöf, V., Öberg, Å., Stenling, R., . . . Wikberg, M. L. (2014). SOX2 expression is regulated by BRAF and contributes to poor patient prognosis in colorectal cancer. PLoS ONE, 9(7), Article ID e101957.
Open this publication in new window or tab >>SOX2 expression is regulated by BRAF and contributes to poor patient prognosis in colorectal cancer
Show others...
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, article id e101957Article in journal (Refereed) Published
Abstract [en]

Sporadic colorectal cancer (CRC) is a common malignancy and also one of the main causes of cancer deaths worldwide. Aberrant expression of the transcription factor SOX2 has recently been observed in several cancer types, but its role in CRC has not been fully elucidated. Here we studied the expression of SOX2 in 441 CRC patients by immunohistochemistry and related the expression to clinicopathological and molecular variables and patient prognosis. SOX2 was expressed in 11% of the tumors and was significantly associated to BRAF(V600E) mutation, but not to KRAS mutations (codon 12 and 13). SOX2 positivity was correlated to poor patient survival, especially in BRAF(V600E) mutated cases. In vitro studies showed that cells expressing the constitutively active BRAF(V600E) had increased SOX2 expression, a finding not found in cells expressing KRAS(G12V). Furthermore, blocking downstream BRAF signalling using a MEK-inhibitor resulted in a decreased expression of SOX2. Since SOX2 overexpression has been correlated to increased migration and invasion, we investigated the SOX2 expression in human CRC liver metastasis and found that a SOX2 positive primary CRC also had SOX2 expression in corresponding liver metastases. Finally we found that cells overexpressing SOX2 in vitro showed enhanced expression of FGFR1, which has been reported to correlate with liver metastasis in CRC. Our novel findings suggest that SOX2 expression is partly regulated by BRAF signalling, and an increased SOX2 expression may promote CRC metastasis and mediate a poor patient prognosis.

Place, publisher, year, edition, pages
Public library of science, 2014
Keywords
island methylator phenotype, transcription factor sox2, dna copy number, gene-expression, microsatellite instability, v600e mutation, lung-cancer, stem-cells, carcinoma, growth
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-91747 (URN)10.1371/journal.pone.0101957 (DOI)000338763800054 ()
Available from: 2014-08-20 Created: 2014-08-15 Last updated: 2018-06-07Bibliographically approved
Esberg, A., Löfgren-Burström, A., Öhman, U. & Strömberg, N. (2012). Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts. Infection and Immunity, 80(11), 3869-3879
Open this publication in new window or tab >>Host and bacterial phenotype variation in adhesion of streptococcus mutans to matched human hosts
2012 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 80, no 11, p. 3869-3879Article in journal (Refereed) Published
Abstract [en]

The commensal pathogen Streptococcus mutans uses AgI/II adhesins to adhere to gp340 adsorbed on teeth. Here we analyzed isolates of S. mutans (n = 70 isolates) from caries and caries-free human extremes (n = 19 subjects) by multilocus sequence typing (MLST), AgI/II full-length gene sequencing, and adhesion to parotid saliva matched from the strain donors (nested from a case-control sample of defined gp340 and acidic proline-rich protein [PRP] profiles). The concatenated MLST as well as AgI/II gene sequences showed unique sequence types between, and identical types within, the subjects. The matched adhesion levels ranged widely (40% adhesion range), from low to moderate to high, between subjects but were similar within subjects (or sequence types). In contrast, the adhesion avidity of the strains was narrow, normally distributed for high, moderate, or low adhesion reference saliva or pure gp340 regardless of the sequence type. The adhesion of S. mutans Ingbritt and matched isolates and saliva samples correlated (r = 0.929), suggesting that the host specify about four-fifths (r(2) = 0.86) of the variation in matched adhesion. Half of the variation in S. mutans Ingbritt adhesion to saliva from the caries cases-controls (n = 218) was explained by the primary gp340 receptor and PRP coreceptor composition. The isolates also varied, although less so, in adhesion to standardized saliva (18% adhesion range) and clustered into three major AgI/II groups (groups A, B-1, and B-2) due to two variable V-region segments and diverse AgI/II sequence types due to a set of single-amino-acid substitutions. Isolates with AgI/II type A versus types B-1 and B-2 tended to differ in gp340 binding avidity and qualitative adhesion profiles for saliva gp340 phenotypes. In conclusion, the host saliva phenotype plays a more prominent role in S. mutans adhesion than anticipated previously.

Place, publisher, year, edition, pages
Washington: American Society Microbiology, 2012
National Category
Medical and Health Sciences
Research subject
Immunology
Identifiers
urn:nbn:se:umu:diva-61766 (URN)10.1128/IAI.00435-12 (DOI)000309971600015 ()
Available from: 2012-11-27 Created: 2012-11-26 Last updated: 2018-06-08Bibliographically approved
Lundholm, M., Mayans, S., Motta, V., Löfgren-Burström, A., Danska, J. & Holmberg, D. (2010). Variation in the Cd3 zeta (Cd247) gene correlates with altered T cell activation and is associated with autoimmune diabetes.. Journal of Immunology, 184(10), 5537-5544
Open this publication in new window or tab >>Variation in the Cd3 zeta (Cd247) gene correlates with altered T cell activation and is associated with autoimmune diabetes.
Show others...
2010 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 184, no 10, p. 5537-5544Article in journal (Refereed) Published
Abstract [en]

Tuning of TCR-mediated activation was demonstrated to be critical for lineage fate in T cell development, as well as in the control of autoimmunity. In this study, we identify a novel diabetes susceptibility gene, Idd28, in the NOD mouse and provide evidence that Cd3zeta (Cd247) constitutes a prime candidate gene for this locus. Moreover, we show that the allele of the Cd3zeta gene expressed in NOD and DBA/2 mouse strains confers lower levels of T cell activation compared with the allele expressed by C57BL/6 (B6), BALB/c, and C3H/HeJ mice. These results support a model in which the development of autoimmune diabetes is dependent on a TCR signal mediated by a less-efficient NOD allele of the Cd3zeta gene.

National Category
Immunology in the medical area
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-41762 (URN)10.4049/jimmunol.0904012 (DOI)000277530700014 ()20400699 (PubMedID)
Available from: 2011-04-01 Created: 2011-04-01 Last updated: 2018-06-08Bibliographically approved
Lundholm, M., Motta, V., Löfgren-Burström, A., Duarte, N., Bergman, M.-L., Mayans, S. & Holmberg, D. (2006). Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1. Diabetes, 55(2), 538-544
Open this publication in new window or tab >>Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1
Show others...
2006 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 55, no 2, p. 538-544Article in journal (Refereed) Published
Abstract [en]

Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4), or CD152, is a negative regulator of T-cell activation and has been shown to be associated with autoimmune diseases. Previous work has demonstrated a defect in the expression of this molecule in nonobese diabetic (NOD) mice upon anti-CD3 stimulation in vitro. Using a genetic approach we here demonstrate that a novel locus (Ctex) telomeric on chromosome 1 together with the Idd3 (Il-2) gene confers optimal CTLA-4 expression upon CD3 activation of T-cells. Based on these data, we provide a model for how gene interaction between Idd3 (IL-2), Ctex, and Idd5.1 (Ctla-4) could confer susceptibility to autoimmune diabetes in the NOD mouse. Additionally, we showed that the Ctex and the Idd3 regions do not influence inducible T-cell costimulator (ICOS) protein expression in NOD mice. Instead, as previously shown, higher ICOS levels in NOD mice appear to be controlled by gene(s) in the Idd5.1 region, possibly a polymorphism in the Icos gene itself.

Keywords
Alleles, Animals, Antigens; CD, Antigens; Differentiation/genetics/*metabolism, Cells; Cultured, Chromosomes; Mammalian/*genetics, Diabetes Mellitus/*genetics, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genotype, Interleukin-2/*genetics, Mice, Mice; Inbred C57BL, Mice; Inbred NOD, Physical Chromosome Mapping, Spleen/cytology, Telomere/*genetics
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-15296 (URN)10.2337/diabetes.55.02.06.db05-1240 (DOI)000235178400037 ()16443792 (PubMedID)2-s2.0-33644753940 (Scopus ID)
Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2018-06-09Bibliographically approved
Organisations

Search in DiVA

Show all publications