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  • 1. Order onlineBuy this publication >>
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Circulating Biomarkers in Patients with Head and Neck Cancer and the Influence of Cigarette Smoking2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Head and neck cancer (HNC) is a collective name for heterogeneous tumors located in the head and neck regions for which smoking, alcohol and human papillomavirus (HPV) are documented risk factors. The survival of HNC patients has only improved marginally during the last decade. The most important prognostic factors are tumor size, local spread and distant metastases, tumor node metastasis (TNM) staging. Prognostic biomarkers are needed as a complement to TNM staging.

    The aim for this thesis was to investigate rapid and low cost blood based biomarkers which could indicate the risk of HNC, recurrence of the disease or the survival of HNC patients. Furthermore, the aim was to examine how cigarette smoking influences the levels of biomarkers.

    In paper I, a possible role of plasma cytokines or proteins associated with immune response or inflammation, as biomarkers for the survival of HNC patients was investigated. Higher levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) were detected in plasma of the patients compared with the levels in the controls. The elevated levels of these two biomarkers detected in patients were associated with decreased survival.

    In paper II, the influence of 45 single nucleotide polymorphisms (SNPs) located in 41 genes associated with cell cycle progression, cell death, DNA repair or immune response on cancer risk, tumor recurrence and survival in HNC patients were investigated. SNPs in immune response genes were associated with risk for HNC, an elevated risk for recurrence and a decreased survival in HNC patients.

    In paper III, the influence of cigarette smoking on levels of inflammatory cells, proteins or cytokines/chemokines, microRNAs (miRNAs) and SNPs was analysed in healthy smokers and non-smokers. Higher levels of total white blood cells (WBCs), neutrophils, monocytes, lymphocytes, neutrophil to lymphocyte ratio (NLR), CRP, monocyte chemoattractant protein- 1 (MCP-1) and interferon gamma (IFN-γ) were detected in smokers compared to non-smokers and indicate an inflammatory response. Also, a lower level of oncomiRNA miR-21was detected in smokers. This alteration, in combination with the elevated levels of IFN-γ in smokers could be a protective response to cigarette smoke. The higher levels of IFN-γ in smokers compared to non-smokers were however only detected in individuals with SNP rs2069705 genotype AG/GG. This indicates a genetic association of the levels of IFN-γ.

    In paper IV, the separate effects of cigarette smoking and HNC on inflammatory or immune biomarkers and the impact of high risk human papillomavirus, age and gender were investigated. Comparisons of circulating levels of WBCs and its subpopulations, plasma proteins or cytokines/chemokines between smoking and non-smoking patients, smoking and non-smoking controls and between the patient and control groups were analysed. Smoking had highest impact on elevated levels of WBCs, IFN-γ and MCP-1, and HNC had highest impact on elevated levels of neutrophils, monocytes, NLR, CRP, macrophage inflammatory protein 1 beta and TNF-α.

    In conclusion, host immune response associated parameters could be suitable as biomarkers for the risk of HNC, risk of recurrence or in predicting survival of HNC patients. This thesis show that HNC are associated with systemic inflammatory response and upregulated CRP and TNF-α is related to shorter survival in HNC patients. Additionally, SNPs in immune response genes such as rs1800629 in the TNF-α gene indicates a risk for HNC or an elevated risk for recurrence and a decreased survival in HNC patients. These rapid and low cost blood based biomarkers could be used in combination or as a supplement to established biomarkers in the clinic for a more personalized treatment modality.

    List of papers
    1. Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma.
    Open this publication in new window or tab >>Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma.
    Show others...
    2014 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 140, no 3, p. 515-519Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated.

    METHODS: In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed.

    RESULTS: Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage.

    CONCLUSIONS: Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.

    Keywords
    Head and neck squamous cell carcinoma, Biomarkers, Survival, CRP, TNF-α
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-162092 (URN)10.1007/s00432-014-1592-8 (DOI)24481866 (PubMedID)
    Available from: 2019-11-19 Created: 2019-11-19 Last updated: 2019-11-19Bibliographically approved
    2. Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients
    Open this publication in new window or tab >>Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients
    Show others...
    2017 (English)In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 92, no 3, p. 161-169Article in journal (Refereed) Published
    Abstract [en]

    Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (Hamp;N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian Hamp;N cancer patients and 245 healthy blood donors were enrolled in the study. Results: Ten SNPs were associated with Hamp;N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNF alpha) rs1800629 could have an influence on cancer risk; tumor recurrence as well as survival. Conclusion: Genetic variation of the TNFa rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of Hamp;N cancer patients. (C) 2016 S. Karger AG, Basel

    Place, publisher, year, edition, pages
    KARGER, 2017
    Keywords
    Head and neck cancer; Tumor recurrence; Survival time; Single-nucleotide polymorphisms
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-136217 (URN)10.1159/000452278 (DOI)000395366800005 ()27997918 (PubMedID)
    Note

    Funding Agencies|Jonkoping Clinical Cancer Research Foundation; Futurum; FORSS; Swedish Laryngeal Foundation

    Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2019-11-19
    3. Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated
    Open this publication in new window or tab >>Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated
    Show others...
    2019 (English)In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 24, no 2, p. 180-185Article in journal (Refereed) Published
    Abstract [en]

    Background: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if the levels of inflammatory biomarkers were associated with selected single nucleotide polymorphisms (SNPs). Method: From 39 smokers and 101 non-smokers, levels of total white blood cells (WBCs) and its subpopulations, plasma cytokines/chemokines/proteins and miRNAs were analysed. For three biomarkers, C-reactive protein (CRP), MCP-1 and IFN-gamma that were affected by smoking, the influence of SNPs was analyzed. Result: Elevated levels of total WBCs, neutrophils, monocytes, lymphocytes, CRP, MCP-1, IFN-gamma and lower levels of miR-21 were detected in smokers. The elevated levels of IFN-gamma in smokers was only statistically significantly associated with rs2069705 AG/GG SNP-genotype. Conclusions: A lower level of oncomir miRNA-21 and a higher level of immune modelling cytokine IFN-gamma detected in smokers could be a protective immune response to cigarette smoke. The higher level of IFN-gamma in smokers with a specific SNP genotype also suggests that a genetic interaction with smoking might predict the pathobiology of smoking related disease.

    Place, publisher, year, edition, pages
    TAYLOR & FRANCIS LTD, 2019
    Keywords
    Immune respons; single nucleotide polymorphism; microRNA; smoking related diseases; cigarette smoking
    National Category
    Rheumatology and Autoimmunity
    Identifiers
    urn:nbn:se:liu:diva-157272 (URN)10.1080/1354750X.2018.1539764 (DOI)000465158700011 ()30375257 (PubMedID)
    Note

    Funding Agencies|Forskningsradet i Sydostra Sverige; Futurum-Academy of HealthCare at Jonkoping County Council [477461, 490031, 669631]; Foundation of Clinical Cancer Research in Jo nkoping [110426-1]; Medical Research Council of Southeast Sweden (FORSS) [567001]

    Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-11-19
    4. Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers
    Open this publication in new window or tab >>Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers
    Show others...
    2020 (English)In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 98, no 1, p. 42-47Article in journal (Refereed) Published
    Abstract [en]

    INTRODUCTION: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients.

    OBJECTIVES: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers.

    METHODS: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers.

    RESULTS: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels.

    CONCLUSION: Identifying HNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.

    Place, publisher, year, edition, pages
    S. Karger, 2020
    Keywords
    Biomarkers, Head and neck squamous cell carcinoma, Immune response, Inflammation, Smoking
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-162093 (URN)10.1159/000502651 (DOI)000522873100007 ()31437849 (PubMedID)
    Note

    Funding agencies: 

    Futurum-Academy of HealthCare at Jonkoping County Council [696261]; Foundation of Clinical Cancer Research in Jonkoping [110426]

    Available from: 2019-11-19 Created: 2019-11-19 Last updated: 2020-04-21Bibliographically approved
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  • 2.
    Andersson, Bengt-Åke
    et al.
    Microbiology Laboratory, Division of Medical Services, Department of Laboratory Services, Ryhov County Hospital, Jönköping.
    Lewin, Freddi
    Department of Oncology, Ryhov County Hospital, Jönköping.
    Lundgren, Jan
    Department of ENT, Karolinska University Hospital, Stockholm.
    Nilsson, Mats
    Futurum - The Academy for Healthcare, County Council, Ryhov County Hospital, Jönköping.
    Rutqvist, Lars-Erik
    Department of Scientific Affairs, Swedish Match AB, Stockholm.
    Löfgren, Sture
    Microbiology Laboratory, Division of Medical Services, Department of Laboratory Services, Ryhov County Hospital, Jönköping.
    Laytragoon-Lewin, Nongnit
    Microbiology Laboratory, Division of Medical Services, Department of Laboratory Services, Ryhov County Hospital, Jönköping.
    Plasma tumor necrosis factor-α and C-reactive protein as biomarker for survival in head and neck squamous cell carcinoma.2014In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 140, no 3, p. 515-519Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Tumor TNM staging is the main basis for prognosis and treatment decision for head and neck squamous cell carcinoma (HNSCC) despite significant heterogeneity in terms of outcome among patients with the same clinical stage. In this study, a possible role of plasma interleukin-2 (IL-2), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) as biomarkers for survival of HNSCC patients was investigated.

    METHODS: In this prospective study, plasma levels of IL-2, IL-6, GM-CSF, TNF-α and CRP in patients (n = 100) and controls (n = 48) were analyzed.

    RESULTS: Significantly elevated levels of CRP and TNF-α (p < 0.001) were found in the patients. Combination of upregulated CRP and TNF-α in the patient plasma was significantly related to shorter patient survival, independent of clinical stage.

    CONCLUSIONS: Our findings indicate that CRP and TNF-α might be suitable as biomarkers in combination with tumor TNM staging for predicting survival and individualized treatment of HNSCC patients. Plasma CRP and TNF-α analysis are simple, rapid, cost effective and suitable for clinical practice.

  • 3.
    Andersson, Bengt-Åke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Löfgren, Sture
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Lewin, Freddi
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology, Region Jönköping County.
    Nilsson, Mats
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Futurum, Academy for Health and Care, Jönköping.
    Laytragoon-Lewin, Nongnit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Region Jönköping County.
    Impact of Cigarette Smoking and Head and Neck Squamous Cell Carcinoma on Circulating Inflammatory Biomarkers2020In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 98, no 1, p. 42-47Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Smoking induces inflammation and an immune response. A cancer-related inflammatory response has been seen in smoking and nonsmoking head and neck squamous cell carcinoma (HNSCC) patients.

    OBJECTIVES: The aim of this study was to analyze the possible separated effects of smoking or HNSCC on 18 inflammatory or immune regulatory biomarkers.

    METHODS: Fifty-one nonsmoking and 36 smoking pretreated HNSCC patients and 101 nonsmoking and 39 smoking controls were included in this study. The levels of 18 inflammatory or immune regulatory biomarkers were analyzed. A multivariable linear regression model was used to predict the impact of smoking and HNSCC on the levels of the biomarkers.

    RESULTS: Smoking had the highest impact on total WBC, IFN-γ, and MCP-1 levels. The highest impact of HNSCC was found on neutrophils, neutrophil-to-lymphocyte ratio, HsCRP, MIP-1b, and TNF-α levels.

    CONCLUSION: Identifying HNSCC or smoking-related inflammatory biomarkers might contribute to the understanding of the immune response in HNSCC patients. This study could provide information of inflammatory biomarkers in HNSCC patients.

  • 4.
    Andersson, Bengt-Åke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Sayardoust, Shariel
    Inst Postgrad Dent Educ, Sweden.
    Lofgren, Sture
    Ryhov Cty Hosp, Sweden.
    Rutqvist, Lars Erik
    Swedish Match AB, Sweden.
    Lewin, Nongnit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated2019In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 24, no 2, p. 180-185Article in journal (Refereed)
    Abstract [en]

    Background: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if the levels of inflammatory biomarkers were associated with selected single nucleotide polymorphisms (SNPs). Method: From 39 smokers and 101 non-smokers, levels of total white blood cells (WBCs) and its subpopulations, plasma cytokines/chemokines/proteins and miRNAs were analysed. For three biomarkers, C-reactive protein (CRP), MCP-1 and IFN-gamma that were affected by smoking, the influence of SNPs was analyzed. Result: Elevated levels of total WBCs, neutrophils, monocytes, lymphocytes, CRP, MCP-1, IFN-gamma and lower levels of miR-21 were detected in smokers. The elevated levels of IFN-gamma in smokers was only statistically significantly associated with rs2069705 AG/GG SNP-genotype. Conclusions: A lower level of oncomir miRNA-21 and a higher level of immune modelling cytokine IFN-gamma detected in smokers could be a protective immune response to cigarette smoke. The higher level of IFN-gamma in smokers with a specific SNP genotype also suggests that a genetic interaction with smoking might predict the pathobiology of smoking related disease.

  • 5.
    Lewin, Nongnit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hospital, Sweden.
    Cederblad, Lena
    University of Uppsala Hospital, Sweden.
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hospital, Sweden.
    Olin, Mattias
    Ryhov Hospital, Sweden.
    Nilsson, Mats
    Ryhov Hospital, Sweden.
    Rutqvist, Lars Erik
    Karolinska University Hospital, Sweden.
    Lundgren, Jan
    Karolinska University Hospital, Sweden.
    Engström, Mats
    University of Uppsala Hospital, Sweden.
    Tytor, Wieslaw
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Löfgren, Sture
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lewin, Freddi
    Ryhov Hospital, Sweden.
    Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients2017In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 92, no 3, p. 161-169Article in journal (Refereed)
    Abstract [en]

    Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (Hamp;N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian Hamp;N cancer patients and 245 healthy blood donors were enrolled in the study. Results: Ten SNPs were associated with Hamp;N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNF alpha) rs1800629 could have an influence on cancer risk; tumor recurrence as well as survival. Conclusion: Genetic variation of the TNFa rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of Hamp;N cancer patients. (C) 2016 S. Karger AG, Basel

  • 6.
    Lewin, Nongnit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hospital, Sweden.
    Lewin, Freddi
    Ryhov Hospital, Sweden.
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hospital, Sweden.
    Löfgren, Sture
    Ryhov Hospital, Sweden.
    Rutqvist, Lars Erik
    Swedish Match AB, Sweden.
    The use of rapid and cost-effective blood-based biomarkers in combination with tumour TNM stage for individual head and neck cancer patient treatment selection2017In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Medical Oncology, ISSN 1357-0560, Vol. 34, no 4, article id 63Article, review/survey (Refereed)
    Abstract [en]

    Head and neck (Hamp;N) cancer is an aggressive disease and the incidence has increased in younger population worldwide. Tumour TNM staging is the main basis for treatment decision despite significant variation in clinical outcome. Survival time of these patients has marginally improved during the last 30 years. Various biomarkers with cumbersome analysis, high cost, time consumption and requirement of special laboratory facilities have been investigated. However, none of these biomarkers have been shown to be suitable to use for individual Hamp;N cancer patient treatment selection in the clinic. For practical use in clinical settings, the given biomarkers must be simple to analyse, rapid, cost effective and available in routine laboratories. With this intension, we suggested the combination of standard TNM staging and biomarkers associated with inflammation such as neutrophils, neutrophil to lymphocyte ratio, plasma C-reactive protein or plasma tumour necrosis factor alpha (TNFa) and single-nucleotide polymorphism in TNFa rs1800629 using blood-based analysis. The optimal treatment outcome of Hamp;N cancer by using combination of TNM stage and these blood-based biomarkers for individual patient selection need further investigation.

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    fulltext
  • 7.
    Lewin, Nongnit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Luetragoon, Thitiya
    Ryhov Hosp, Sweden; Naresuan Univ, Thailand.
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Oliva, Delmy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Nilsson, Mats
    Ryhov Hosp, Sweden.
    Strandeus, Michael
    Ryhov Hosp, Sweden.
    Lofgren, Sture
    Ryhov Hosp, Sweden.
    Rutqvist, Lars-Erik
    Swedish Match AB, Sweden.
    Lewin, Freddi
    Ryhov Hosp, Sweden.
    The Influence of Single Nucleotide Polymorphisms and Adjuvant Radiotherapy on Systemic Inflammatory Proteins, Chemokines and Cytokines of Patients With Breast Cancer2019In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 39, no 3, p. 1287-1292Article in journal (Refereed)
    Abstract [en]

    Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. Materials and Methods: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. Results: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. Conclusion: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.

  • 8.
    Lewin, Nongnit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Luetragoon, Thitiya
    Ryhov Hosp, Sweden; Naresuan Univ, Thailand.
    Shamoun, Levar
    Ryhov Hosp, Sweden.
    Oliva, Delmy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Lofgren, Sture
    Ryhov Hosp, Sweden.
    Rutqvist, Lars Erik
    Swedish Match AB, Sweden.
    Lewin, Freddi
    Ryhov Hosp, Sweden.
    The Influence of Adjuvant Radiotherapy and Single Nucleotide Polymorphisms on Circulating Immune Response Cell Numbers and Phenotypes of Patients With Breast Cancer2019In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 39, no 9, p. 4957-4963Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. Materials and Methods: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. Results: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. Conclusion: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.

  • 9.
    Luetragoon, Thitiya
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory Medicine, Ryhov Hospital, Jönköping, Sweden; Department of Medical Technology, Naresuan University, Phitsanulok, Thailand.
    Rutqvist, Lars E.
    Swedish Match AB, Sweden.
    Tangvarasittichai, Orathai
    Naresuan Univ, Thailand.
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Löfgren, Sture
    Ryhov Hosp, Sweden.
    Usuwanthim, Kanchana
    Naresuan Univ, Thailand.
    Lewin, Nongnit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals2018In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 154, no 1, p. 98-103Article in journal (Refereed)
    Abstract [en]

    Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never-users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C-reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8(dim) cells in the lymphocyte group, CD13(+)CD11(+), CD13(+)CD14(+), CD13(+)CD56(+) cells in the monocyte group and CD13(+)CD11(+), CD13(+)CD56(+) cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8(+)GZB(+) cells in the CD8(dim) group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking-related disease and the variations observed in clinical outcomes.

  • 10.
    Oliva, Delmy
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology, Ryhov County Hospital, SE-551 85 Jönköping, Sweden.
    Nilsson, Mats
    Futurum – The Academy for Healthcare, Region Jönköping County, SE-551 85 Jönköping, Sweden.
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Division of Medical Diagnostics, Region Jönköping County, SE-551 85 Jönköping, Sweden.
    Sharp, Lena
    Regional Cancer Centre, Stockholm-Gotland, SE-10239 Stockholm, Sweden / Karolinska Institutet, Department of Learning, Informatics Management and Ethics, SE-171 77 Stockholm, Sweden.
    Lewin, Freddi
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology, Ryhov County Hospital, SE-551 85 Jönköping, Sweden.
    Laytragoon-Lewin, Nongnit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Single nucleotide polymorphisms might influence chemotherapy induced nausea in women with breast cancer2017In: Clinical and Translational Radiation Oncology, ISSN 2405-6308, Vol. 2, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Background Women receiving FEC (5 fluorouracil, epirubicin and cyclophosphamide) chemotherapy (CT) for breast cancer (BC) often experience side effects such as nausea and vomiting. Individual variations of side effects occur in patients despite similar cancer therapy. The purpose of this study was to investigate a possible genetic background as a predictor for individual variations in nausea induced by CT. Methods 114 women were included in the study. All women received adjuvant CT for BC. Self-reported nausea and vomiting was recorded in a structured diary over ten days following treatment. Blood samples were collected before the treatment and used for the detection of 48 single nucleotide polymorphisms (SNPs) in 43 genes. SNPs from each individual woman were analyzed for their relation to the patient-reported frequency and intensity of nausea and vomiting. Results Eighty-four percent (n=96) of the women reported acute or delayed nausea or combined nausea and vomiting during the ten days following CT. Three out of the forty-eight SNPs in the following genes: FAS/CD95, RB1/LPAR6 and CCL2 were found to be associated with a risk of nausea. Conclusion SNPs in the FAS/CD95, RB1/LPAR6 and CCL2 genes were found to be associated with nausea among women treated with adjuvant FEC for BC. SNPs analysis is fast and cost effective and can be done prior to any cancer therapy. The association between individual SNPs and severe side effects from FEC may contribute to a more personalized care of patients with BC.

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    Single nucleotide polymorphisms might influence chemotherapy induced nausea in women with breast cancer
  • 11.
    Oliva, Delmy
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology, Ryhov County Hospital, Jönköping, Sweden .
    Nilsson, Mats
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Futurum-The Academy for Healthcare, Region Jönköping County, Jönköping, Sweden.
    Strandeus, Michael
    Department of Oncology, Ryhov County Hospital, Jönköping, Sweden.
    Andersson, Bengt-Åke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory medicine, Region Jönköping County, Jönköping, Sweden.
    Sharp, Lena
    Regional Cancer Centre, Stockholm-Gotland, Stockholm, Sweden / Department of Learning, Informatics, Management and Ethics, Karolinska Institute, Stockholm, Sweden .
    Lewin, Nongnit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Laboratory medicine, Region Jönköping County, Jönköping, Sweden.
    Lewin, Freddi
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Oncology, Ryhov County Hospital, Jönköping, Sweden.
    Individual Genetic Variation Might Predict Acute Skin Reactions in Women Undergoing Adjuvant Breast Cancer Radiotherapy2018In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 38, no 12, p. 6763-6770Article in journal (Refereed)
    Abstract [en]

    Adverse skin reactions during radiotherapy (RT) are common. The aim of this study was to explore whether genetic variation might be linked to acute radiation skin reactions (ARSR). Materials and Methods: One hundred and nineteen women undergoing adjuvant RT for breast cancer were included. The symptoms of itching, burning and irritation were self-reported twice using the visual analogue scale. Assessments used the Radiation Therapy Oncology Group scoring system for acute RT skin reaction (RTOG scale). Blood-based single nucleotide polymorphism (SNP) analysis was performed. Thirty SNPs of well-defined functional genes were investigated. Results: All women were assessed with ARSR. After RT, the women self-reported itching (n=97), burning (n=64) and irritation (n=96). Two SNPs in X-Ray Repair Cross Complementing 2 gene (XRCC2) rs2040639 and interferon gamma (IFNG) rs2069705 genes were found to be associated with ARSR. Conclusion: An association between two SNPs and ARSR was found. The possibility of using these SNPs as prognostic biomarkers for ARSR as tools to improve the care of patients needs further investigation.

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