liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 30 of 30
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Barczyk, K.
    et al.
    Department of Immunology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland; Institute of Experimental Dermatology, University of Münster, Münster, Germany.
    Kreuter, M.
    Department of Medicine/Hematology and Oncology, University of Münster, Münster, Germany.
    Pryjma, J.
    Department of Immunology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland.
    Booy, Evan P.
    Manitoba Institute of Cell Biology, and Department of Biochemistry and Medical Genetics, Univ. Manitoba, Winnipeg, Canada.
    Maddika, Subbareddy
    Manitoba Institute of Cell Biology, Cancer Care Manitoba; Department of Biochemistry and Medical Genetics,University of Manitoba, Winnipeg, Canada .
    Ghavami, Saeid
    Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada.
    Berdel, W. E.
    Department of Medicine/Hematology and Oncology, University of Münster, Münster, Germany.
    Roth, J.
    Institute of Experimental Dermatology, University of Münster, Münster, Germany.
    Los, Marek Jan
    Institute of Experimental Dermatology, University of Münster, Münster, Germany Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada, .
    Serum cytochrome c indicates in vivo apoptosis and can serve as a prognostic marker during cancer therapy2005In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 116, no 2, p. 167-173Article in journal (Refereed)
    Abstract [en]

    Despite significant progress in cancer therapy, the outcome of the treatment is often unfavorable. Better treatment monitoring would not only allow an individual more effective, patient-adjusted therapy, but also it would eliminate some of the side effects. Using a cytochrome c ELISA that was modified to increase sensitivity, we demonstrate that serum cytochrome c is a sensitive apoptotic marker in vivo reflecting therapy-induced cell death burden. Furthermore, increased serum cytochrome c level is a negative prognostic marker. Cancer patients whose serum cytochrome c level was normal 3 years ago have a twice as high probability to be still alive, as judged from sera samples collected for years, analyzed recently and matched with survival data. Moreover, we show that serum cytochrome c and serum LDH-activity reflect different stages and different forms of cell death. Cellular cytochrome c release is specific for apoptosis, whereas increased LDH activity is an indicator of (secondary) necrosis. Whereas serum LDH activity reflects the "global" degree of cell death over a period of time, the sensitive cytochrome c-based method allows confirmation of the individual cancer therapy-induced and spontaneous cell death events. The combination of cytochrome c with tissue-specific markers may provide the foundation for precise monitoring of apoptosis in vivo, by "lab-on-the-chip" technology. (c) 2005 Wiley-Liss, Inc.

  • 2.
    Bergman-Jungeström, Malin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gentile, Massiliano
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Lundin, Anna-Carin
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Association between CYP17 gene polymorphism and risk of breast cancer in young women1999In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 84, p. 350-353Article in journal (Refereed)
    Abstract [en]

    Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T→C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1–3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1.9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41–1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women.

  • 3. Bistoletti, P.
    et al.
    Sennfält, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment.
    Dillner, J.
    Department of Medical Microbiology, Lund University, MAS University Hospital, Malmö, Sweden, Department of Medical Microbiology, Lund University, MAS University Hospital, SE-20502 Malmö, Sweden.
    Cost-effectiveness of primary cytology and HPV DNA cervical screening2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 122, no 2, p. 372-376Article in journal (Refereed)
    Abstract [en]

    Because cost-effectiveness of different cervical cytology screening strategies with and without human papillomavirus (HPV) DNA testing is unclear, we used a Markov model to estimate life expectancy and health care cost per woman during the remaining lifetime for 4 screening strategies: (i) cervical cytology screening at age 32, 35, 38, 41, 44, 47, 50, 55 and 60, (ii) same strategy with addition of testing for HPV DNA persistence at age 32, (iii) screening with combined cytology and testing for HPV DNA persistence at age 32, 41 and 50, iv) no screening. Input data were derived from population-based screening registries, health-service costs and from a population-based HPV screening trial. Impact of parameter uncertainty was addressed using probabilistic multivariate sensitivity analysis. Cytology screening between 32 and 60 years of age in 3-5 year intervals increased life expectancy and life-time costs were reduced from 533 to 248 US Dollars per woman compared to no screening. Addition of HPV DNA testing, at age 32 increased costs from 248 to 284 US Dollars without benefit on life expectancy. Screening with both cytology and HPV DNA testing, at ages 32, 41 and 50 reduced costs from 248 to 210 US Dollars with slightly increased life expectancy. In conclusion, population-based, organized cervical cytology screening between ages 32 to 60 is highly cost-efficient for cervical cancer prevention. If screening intervals are increased to at least 9 years, combined cytology and HPV DNA screening appeared to be still more effective and less costly. © 2007 Wiley-Liss, Inc.

  • 4. Bochicchio, Francesco
    et al.
    Forastiere, Francesco
    Farchi, Sara
    Quarto, Maria
    Axelson, Olav
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Residential radon exposure, diet and lung cancer: A case-control study in a Mediterranean region2005In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 114, no 6, p. 983-991Article in journal (Refereed)
    Abstract [en]

    We performed a case-control study in Lazio, a region in central Italy characterized by high levels of indoor radon, Mediterranean climate and diet. Cases (384) and controls (404) aged 35-90 years were recruited in the hospital. Detailed information regarding smoking, diet and other risk factors were collected by direct interview. Residential history during the 30-year period ending 5 years before enrolment was ascertained. In each dwelling, radon detectors were placed in both the main bedroom and the living room for 2 consecutive 6-month periods. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for time-weighted radon concentrations using both categorical and continuous unconditional logistic regression analysis and adjusting for smoking, diet and other variables. Radon measurements were available from 89% and 91% of the time period for cases and controls, respectively. The adjusted ORs were 1.30 (1.03-1.64), 1.48 (1.08-2.02), 1.49 (0.82-2.71) and 2.89 (0.45-18.6) for 50-99, 100-199, 200-399 and 400+ Bq/m3, respectively, compared with 0-49 Bq/m3 (OR = 1, 0.56-1.79). The excess odds ratio (EOR) per 100 Bq/m3 was 0.14 (-0.11, 0.46) for all subjects, 0.24 (-0.09, 0.70) for subjects with complete radon measurements and 0.30 (-0.08, 0.82) for subjects who had lived in 1 or 2 dwellings. There was a tendency of higher risk estimates among subjects with low-medium consumption of dietary antioxidants (EOR = 0.32, -0.19, 1.16) and for adenocarcinoma, small cell and epidermoid cancers. This study indicates an association, although generally not statistically significant, between residential radon and lung cancer with both categorical and continuous analyses. Subjects with presumably lower uncertainty in the exposure assessment showed a higher risk. Dietary antioxidants may act as an effect modifier. © 2005 Wiley-Liss, Inc.

  • 5.
    Dabrosin, Charlotta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Margetts, Peter J
    Gauldie, Jack
    Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer2003In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 107, no 4, p. 535-540Article in journal (Refereed)
    Abstract [en]

    Angiogenesis is essential for tumor growth and metastasis and an important prognostic factor in breast cancer. VEGF, a key factor for angiogenesis, has been correlated with tumor vessel density in breast cancer. Estrogen, another crucial factor in breast cancer, stimulates VEGF, and an ERE in the VEGF gene has been defined. VEGF is bioactive in the extracellular fluid, where it becomes available to endothelial cells. Whether E2 affects VEGF levels in the extracellular fluid is not known. We show, using intratumoral microdialysis in vivo, that E2 treatment increased tumor extracellular levels of VEGF in an estrogen-dependent breast cancer model. Moreover, extracellular levels of VEGF in the tumor showed a strong correlation with total tumor VEGF, contrary to plasma levels of VEGF. Ninety-three percent of measured VEGF in the extracellular fluid in the tumor was tumor-derived, while only 45% of VEGF in circularing plasma originated from the tumor. We conclude that E2 increases extracellular VEGF and that microdialysis is a sensitive method for measurement of local VEGF production in vivo. Our results have potential application to the assessment of tumor characteristics in vivo in human tumors for individualized cancer therapy.

  • 6.
    Eriksson, Hanna
    et al.
    Department of Oncology-Pathology, Karolinska Institutet, and Deptartment of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Andersson, Therese M-L
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    The proportion cured of patients diagnosed with Stage III-IV cutaneous malignant melanoma in Sweden 1990-2007: A population-based study.2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 12Article in journal (Refereed)
    Abstract [en]

    The survival in cutaneous malignant melanoma (CMM) is highly dependent on the stage of the disease. Stage III-IV CMM patients are at high risk of relapse with a heterogeneous outcome, but not all experience excess mortality due to their disease. This group is referred to as the cure proportion representing the proportion of patients who experience the same mortality rate as the general population. The aim of this study was to estimate the cure proportion of patients diagnosed with Stage III-IV CMM in Sweden. From the population-based Swedish Melanoma Register, we included 856 patients diagnosed with primary Stage III-IV CMM, 1990-2007, followed-up through 2013. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by sex, age, tumor site, ulceration status (in Stage III patients) and disease stage. The standardized (over sex, age and site) cure proportion was lower in Stage IV CMMs (0.15, 95% CI 0.09-0.22) than non-ulcerated Stage III CMMs (0.48, 95% CI 0.41-0.55) with a statistically significant difference of 0.33 (95% CI = 0.24-0.41). Ulcerated Stage III CMMs had a cure proportion of 0.27 (95% CI 0.21-0.32) with a statistically significant difference compared to non-ulcerated Stage III CMMs (difference 0.21; 95% CI = 0.13-0.30). The standardized MST of uncured was approximately 9-10 months longer for non-ulcerated versus ulcerated Stage III CMMs. We could demonstrate a significantly better outcome in patients diagnosed with non-ulcerated Stage III CMMs compared to ulcerated Stage III CMMs and Stage IV disease after adjusting for age, sex and tumor site.

  • 7.
    Farnebo, Lovisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Tiefenböck, Katharina
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ansell, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences.
    Thunell, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Garvin, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 8, p. 1994-2003Article in journal (Refereed)
    Abstract [en]

    Head and neck squamous cell carcinoma (HNSCC) is a malignancy that is associated with severe mortality despite advances in therapy. Todays standard treatment most commonly includes radiotherapy, often combined with chemotherapy or surgery. There are so far no established biomarkers to predict response to radiation, and thus the aim of this study was to investigate a series of markers that could potentially identify HNSCC patients who would benefit from radiotherapy. The selected markers, both proteins (epidermal growth factor receptor, survivin and p53), and single nucleotide polymorphisms (SNPs) in the genes of XRCC3, XRCC1, XPC, XPD, MDM2, p53 and FGFR4 were correlated to the response to radiotherapy and overall survival. Investigations were performed on pretreatment tumor biopsies from patients classified as responders or nonresponders to radiotherapy. Protein expression was examined using immunohistochemistry and the genotyping of specific SNPs was analyzed using PCR-RFLP or pyrosequencing. We found that survivin expression was significantly stronger in the responder group (p = 0.003) and that patients with a strong survivin expression had a significantly better overall survival (p andlt; 0.001). Moreover, downregulation of survivin by siRNA in two HNSCC cell lines significantly decreased their sensitivity to radiation. Among the SNPs analyzed, patients with the XPD Lys751Gln SNP had a significantly shorter overall survival (p = 0.048), and patients with the FGFR4 Gly388Arg SNP had a significantly longer overall survival (p = 0.010). In conclusion, our results suggest that survivin plays an important role in the response to radiotherapy and may be a useful marker for predicting radiotherapy response in patients with HNSCC. less thanbrgreater than less thanbrgreater thanWhats new? Resistance to radiation therapy is a significant problem in the treatment of head and neck squamous cell carcinoma (HNSCC) and has created a need for the discovery of markers predictive of radiotherapy response. One promising marker is survivin, an inhibitor of apoptosis. Here, in pre-treatment biopsies from 40 patients with HNSCC, strong survivin expression was significantly associated with response to radiotherapy and increased overall survival. The data also indicate that single nucleotide polymorphisms in the genes XPD and FGFR4 are other possible predictors of overall survival after radiotherapy.

  • 8.
    Fulda, S.
    et al.
    Hematology/Oncology, University Children's Hospital and Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany.
    Los, Marek Jan
    Hematology/Oncology, University Children's Hospital and Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany.
    Friesen, C.
    Hematology/Oncology, University Children's Hospital and Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany.
    Debatin, K. M.
    Hematology/Oncology, University Children's Hospital and Division of Molecular University Children's Hospital, Prittwitzstr. 43, D-89075 Ulm, Germany.
    Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system1998In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 76, no 1, p. 105-114Article in journal (Refereed)
    Abstract [en]

    We have identified the CD95 system as a key mediator of chemotherapy-induced apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity of various solid tumor cell lines for drug-induced cell death corresponds to activation of the CD95 system, Upon drug treatment, strong induction of CD95 ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not in tumor cells which responded poorly to drug treatment (breast carcinoma and renal cell carcinoma). Blockade of CD95 using F(ab')(2) anti-CD95 antibody fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment induced CD95 expression, thereby increasing sensitivity for CD95-induced apoptosis, Drug-induced apoptosis critically depended on activation of caspases (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD-fmk strongly reduced drug-mediated apoptosis, The prototype substrate of caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment, suggesting that CD95-L triggered autocrine/paracrine death via activation of caspases, Our data suggest that chemosensitivity of solid tumor cells depends on intact apoptosis pathways involving activation of the CD95 system and processing of caspases. Our findings may have important implications for new treatment approaches to increase sensitivity and to overcome resistance of solid tumors. (C) 1998 Wiley-Liss, Inc.

  • 9.
    Gentile, Massimiliano
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Wiman, Åsa
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Thorstenson, Sten
    Department of Pathology and Cytology, Kalmar County Hospital, Kalmar, Sweden.
    Loman, Niklas
    Department of Oncology, Jubileum Institute, University Hospital, Lund, Sweden.
    Borg, Åke
    Department of Oncology, Jubileum Institute, University Hospital, Lund, Sweden.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer2001In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 92, no 2, p. 208-213Article in journal (Refereed)
    Abstract [en]

    Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the consecutive patients, extensive LOH was observed for all markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D11S387 marker correlated with higher histologic grade (p = 0.042). In the familial cases, the most telomeric markers showed substantially lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer. Our data suggest that the most probable position for this locus is defined by the markers D11S387 and D11S4125 and furthermore that it may play a less significant role in familial breast cancer cases not linked to either of the BRCA genes.

  • 10.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gentile, Massamiliano
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    p53 mutations are present in colorectal cancer with cytoplasmic p53 accumulation2001In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 92, no 3, p. 338-341Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that nuclear p53 over-expression is an indicator of p53 mutations whereas cytoplasmic p53 accumulation is related to wild-type p53 in several kinds of tumors. Cytoplasmic p53 accumulation has been demonstrated to be an independent prognostic factor in colorectal adenocarcinomas. The purpose was to examine whether mutations occur in cases with p53 accumulated in the cytoplasm and whether there are any differences in the frequency and characteristics of p53 mutations in different staining patterns. In the present study, we identified p53 mutations using PCR single-strand conformation polymorphism (SSCP) and DNA sequencing in 75 primary colorectal adenocarcinomas with different staining patterns (negative, nucleus, cytoplasm, nucleus and cytoplasm). The results show that the frequency and nature of mutations in tumors with cytoplasmic p53 accumulation were similar to those with nuclear p53 expression. However, the tumors with accumulation in both the nucleus and cytoplasm demonstrated a higher mutation rate. We suppose that the role of cytoplasmic p53 accumulation in predicting prognosis in patients with colorectal cancer may be dependent on both mutational and non-mutational mechanisms.

  • 11.
    Jarbo, Caroline
    et al.
    Rudbeck Laboratory, Uppsala University, Sweden.
    Buckley, Patrick
    Rudbeck Laboratory, Uppsala University, Sweden.
    Piotrowski, Arkadiusz
    Rudbeck Laboratory, Uppsala University, Sweden.
    Mantripragada, Kiran
    Rudbeck Laboratory, Uppsala University, Sweden.
    Benetkiewicz, Magdalena
    Rudbeck Laboratory, Uppsala University, Sweden.
    Diaz de Ståhl, Teresita
    Rudbeck Laboratory, Uppsala University, Sweden.
    Langford, Cordelia
    The Wellcome Trust Sanger Institute, Cambridge, UK.
    Gregory, Simon
    The Wellcome Trust Sanger Institute, Cambridge, UK.
    Dralle, Henning
    Martin Luther University of Halle, Germany.
    Gimm, Oliver
    Martin Luther University of Halle, Germany.
    Bäckdahl, Martin
    Karolinska University Hospital, Stockholm, Sweden.
    Geli, Janos
    Karolinska University Hospital, Stockholm, Sweden.
    Larsson, Catharina
    Karolinska University Hospital, Stockholm, Sweden.
    Westin, Gunnar
    Uppsala University Hospital, Sweden.
    Åkerström, Göran
    Uppsala University Hospital, Sweden.
    Dumanski, Jan
    Rudbeck Laboratory, Uppsala University, Sweden.
    Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 118, no 5, p. 1159-1164Article in journal (Refereed)
    Abstract [en]

    Pheochromocytoma is a predominantly sporadic neuroendocrine tumor derived from the adrenal medulla. Previous low resolution LOH and metaphase-CGH studies reported the loss of chromosomes 1p, 3q, 17p and 22q at various frequencies. However, the molecular mechanism(s) behind development of sporadic pheochromocytoma remains largely unknown. We have applied high-resolution tiling-path microarray-CGH with the primary aim to characterize copy number imbalances affecting chromosome 22 in 66 sporadic pheochromocytomas. We detected copy number alterations on 22q at a frequency of 44%. The predominant finding was monosomy 22 (30%), followed by terminal deletions in 8 samples (12%) and a single interstitial deletion. We further applied a chromosome 1 tiling-path array in 7 tumors with terminal deletions of 22q and found deletions of 1p in all cases. Our overall results suggest that at least 2 distinct regions on both 22q and 1p are important in the tumorigenesis of sporadic pheochromocytoma. A large proportion of pheochromocytomas also displayed indications of cellular heterogeneity. Our study is to our knowledge the first array-CGH study of sporadic pheochromocytoma. Future analysis of this tumor type should preferably be performed in the context of the entire human genome using genome-wide array-CGH, which is a superior methodological approach. Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

  • 12.
    Karlsson, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Ungerbäck, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rasmussen, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    French, John E
    National Institute of Environmental Health Science, NC USA.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Notch1 is a frequent mutational target in chemically induced lymphoma in mouse2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, no 11, p. 2720-2724Article in journal (Refereed)
    Abstract [en]

    Activating Notch1 mutations have been reported in human T-lineage acute lymphoblastic leukemia (T-ALL) and lymphomas from genetically modified mice. We report that Notch1 is a prevalent and major mutational target in chemically induced mouse lymphoma. The regions of the gene that are frequently mutated are the hterodimerization domain and the N-terminal ligand-binding region, important for protein stability, and (he polypeptide rich in proline, glutamate, serine and threonine WEST) domains, which is critical for protein degradation. Another gene, CDC4, is also involved in Notch1 degradation and shows frequent mutations. Mutations in the heterodimerization and the ligand-binding regions may cause ligand-independent signaling. whereas mutations preventing protein degradation result in accumulation of intracellular Notch1. We analyzed 103 chemical-induced mouse lymphomas for mutations in the Notch1 gene using single strand conformation analysis (SSCA) and DNA sequencing. Genetic alterations resulting in premature truncation of Notch I were identified in 28 tumors, whereas 8 revealed alterations in the heterodimerization and 16 harbored deletions in the ligand-binding region. Dideoxycytidine-induced lymphomas displayed the highest frequency of Notch1 mutations (49%). whereas in butadiene- and phenolphthalein-indced tumors showed lower frequencies (26 10%, respectively). In total, 26 novel and 3 previously reported mutations were detected. This report shows that Notch1 is a prevalent and major mtational target for 2,3-dideoxycytidine and butadiene-induced lymphoma..

  • 13.
    Karlsson, Pia M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Cutaneous malignant melanoma in children and adolescents in Sweden, 1993–2002: the increasing trend is broken2007In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 121, no 2, p. 323-328Article in journal (Refereed)
    Abstract [en]

    The incidence of cutaneous malignant melanoma rose rapidly in teenagers in Sweden during 1973-1992, while it remained low in younger children. To study the further trends and characteristics of melanoma in this young population, data on all cases in individuals under 20 years of age reported to the Swedish Cancer Registry during 1993-2002, and the corresponding pathology reports were examined. Seventy-nine cases were reported to the Registry. There were 24 males and 55 females. Most melanomas occurred on the trunk followed by the legs in both genders. The median tumor thickness was 0.8 mm. Children under age 15 had thicker melanomas than individuals aged 15-19. Superficial spreading melanoma was the most common histological subtype (43/78, 55%). The melanoma-specific 5-year survival rate was 90%. During 1993-2002, the age-standardized incidence fell to 3.6/million from 5.0/million in 1983-1992 (RR 0.74, 95% CI 0.58-0.92). The most pronounced decrease was for melanomas on the trunk in boys and on the legs in girls. The incidence for 15-19-year-old boys peaked for the cohort born between 1968 and 1972 and for girls between 1973 and 1977. The decrease in incidence may be a result of public health campaigns aiming at reducing sun exposure in childhood. A contributing effect from an increased immigration of individuals with darker complexions and at a lower melanoma risk is probable.

  • 14. Kronblad, A
    et al.
    Jirström, K
    Rydén, L
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Landberg, G
    Hypoxia inducible factor-1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 118, no 10, p. 2609-2616Article in journal (Refereed)
    Abstract [en]

    Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor-1α (HIF-1α), and HIF-1α has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1α regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1α using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF-1α was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki-67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF-1α expressing tumours. In lymph node-positive patients as well as NHG 1/2 tumours, high HIF-1α protein expression was significantly associated with an impaired recurrence-free survival (p = 0.014, 0.018). When analyzing the subgroup of NHG 1/2 tumours, a high HIF-1α expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF-1α might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis. © 2005 Wiley-Liss, Inc.

  • 15. Nordengren, J
    et al.
    Fredstorp Lidebring, M
    Bendahl, P-O
    Brunner, N
    Fero, M
    Högberg, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Stephens, RW
    Willén, RW
    Casslén, B
    High tumor tissue concentration of plasminogen activator inhibitor-2 (PAI-2) is an independent marker for shorter progression-free survival of patients with early stage endometrial cancer2002In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 97, p. 379-385Article in journal (Refereed)
  • 16.
    Nordlund, Lars Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Pershagen, Göran
    Karolinska institutet, Stockholm.
    Cancer incidence in female smokers: a 26-year follow-up1997In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 73, no 5, p. 625-628Article in journal (Refereed)
    Abstract [en]

    A random sample of 26,000 Swedish women who were asked about their smoking habits in the early 1960s have now been followed for 26 years with respect to cancer incidence. Most findings regarding tobacco smoking and cancer from studies of men were confirmed also among the women. Elevated relative risk for current smokers compared with women who never smoked regularly were seen for cancers of the lung, upper aerodigestive sites, pancreas, bladder, cervix and all cancers combined, as well as a notably high relative risk for cancers of organs of the urinary tract other than kidney and bladder. Relative risk increased with dose, measured as grams of tobacco smoked per day, for cancers of the upper aerodigestive sites, lung, cervix, bladder, organs of the urinary tract other than kidney and bladder and all cancers combined. For cancers of the lung, bladder and cervix, there was an inverse relationship with age when starting to smoke tobacco. The reported inverse relationship between smoking and endometrial cancer could not be corroborated, nor was there any significant relationship between smoking and colorectal or breast cancer.

  • 17.
    Persson, P
    et al.
    Lund University.
    Manetopoulos, C
    Lund University.
    Lagergren, A
    Lund University.
    Nygren, J
    Lund University.
    Gisler, R
    Lund University.
    Axelson, H
    Lund University.
    Sigvardsson, Mikael
    Lund University.
    Olf/EBF proteins are expressed in neuroblastoma cells: Potential regulators of the Chromogranin A and SCG10 promoters2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 110, no 1, p. 22-30Article in journal (Refereed)
    Abstract [en]

    The childhood malignancy neuroblastoma is derived from developmentally arrested sympathetic nervous system precursor cells. To obtain further insight into the molecular processes involved in the formation of these tumors, we decided to investigate the functional role of Olf/EBF (O/E) transcription factors in human neuroblastoma cells. We here report that O/E-1 and O/E-2 are expressed at variable levels in neuroblastoma cell lines and that O/E proteins could be identified by electrophoretic mobility shift assays. To identify potential neuronal target genes for O/E proteins in neuroblastoma cells we investigated the ability of a set of neuronal promoters to interact with O/E-1 in electrophoretic mobility shift assays. This analysis suggested that the Chromogranin A (CgA) and SCG10 promoters both contained binding sites for O/E-1. O/E-1 was able to activate the CgA promoter in vivo and mutation of the O/E-1 binding site in the CgA promoter reduced the functional activity of the element to about 60% of the wild-type in neuroblastoma cells, supporting the idea that O/E proteins may be involved in the control of the CgA promoter. Furthermore, overexpression of O/E-1 in hippocampal progenitor cells led to neurite outgrowth, indicative of a role for O/E proteins in neuronal differentiation.

  • 18.
    Saarinen, Niina M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Abrahamsson, Annelie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Estrogen-induced angiogenic factors derived from stromal and cancer cells are differently regulated by enterolactone and genistein in human breast cancer in vivo2010In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 127, no 3, p. 737-745Article in journal (Refereed)
    Abstract [en]

    Angiogenesis is a key in cancer progression and its regulators are released both by the tumor cells and the stroma. Dietary phytoestrogens, such as the lignan enterolactone (ENL) and the isoflavone genistein (GEN), may differently affect breast cancer growth. In this study, human breast cancer cells (MCF-7) were established in mice creating a tumor with species-specific cancer and stroma cells. Ovariectomized athymic mice supplemented with estradiol (E2) were fed basal AIN-93G diet (BD) or BD supplemented with 100 mg/kg ENL, 100 mg/kg GEN or their combination (ENL+GEN). We show that ENL and ENL+GEN inhibited E2-induced cancer growth and angiogenesis, whereas GEN alone did not. Microdialysis was used to sample extracellular proteins in tumors in vivo. ENL and ENL+GEN decreased both stroma- and cancer cell-derived VEGF, whereas cancer cell-derived PlGF increased. In subcutaneous Matrigel plugs in mice, ENL and ENL+GEN decreased E2-induced endothelial cell infiltration, whereas GEN alone did not. In endothelial cells, ENL inhibited E2-induced VEGFR-2 expression, whereas GEN did not. These results suggest that ENL has potent effects on breast cancer growth, even in combination with GEN, by downregulating E2-stimulated angiogenic factors derived both from the stroma and the cancer cells, whereas dietary GEN does not possess any antiestrogenic effects.

  • 19.
    Settimi, Laura
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Masina, Alceste
    Local Health Unit, Imola, Italy.
    Andrion, Alberto
    Martini Hospital, Turin, Italy.
    Axelson, Olav
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Prostate cancer and exposure to pesticides in agricultural settings2003In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 104, no 4, p. 458-461Article in journal (Refereed)
    Abstract [en]

    Our study evaluates the association between prostate cancer and exposure to pesticides in agricultural settings in Italy. The data were derived from a hospital-based multi-site case-control study carried out in 5 rural areas between 1990–92. In our study, 124 new cases of prostate cancer were ascertained and interviewed, along with 659 cancer controls. A team of agronomists assessed past exposure to pesticides by using a checklist of 100 chemical families and 217 compounds applied from 1950–85 in the areas considered. The association between prostate cancer and different occupational risk factors was measured by maximum likelihood estimation of the odds ratio, controlling for potential confounders. “Ever been employed in agriculture” was associated with a 40% increased risk (OR = 1.4, 95% CI = 0.9–2.0). Prostate cancer was also related positively to food and tobacco (OR= 2.1, 95% CI = 1.1–4.1), and chemical products (OR = 2.2, 95% CI = 0.7–7.2) industries. The analyses carried out to estimate the association between different types of pesticides and prostate cancer showed increased risks among farmers exposed to organochlorine insecticides and acaricides (OR = 2.5, 95% CI = 1.4–4.2), more specifically to the often contemporary used compounds DDT (OR = 2.1, 95% CI = 1.2–3.8), and dicofol (OR = 2.8, 95% CI = 1.5–5.0), whose effects could not be well separated.

  • 20.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Doré, Siv
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, no 4, p. 780-786Article in journal (Refereed)
    Abstract [en]

    Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

  • 21.
    Simberg-Danell, Caroline
    et al.
    Karolinska Institute, Sweden; Soder Sjukhuset, Sweden.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Faculty of Medicine and Health Sciences.
    Mansson-Brahme, Eva
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Frohm-Nilsson, Margareta
    Karolinska University Hospital, Sweden.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Hansson, Johan
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Eriksson, Hanna
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 139, no 3, p. 543-553Article in journal (Refereed)
    Abstract [en]

    Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first-and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR=2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; pamp;lt;0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-horn patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95 h CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis.

  • 22.
    Stålberg, Karin
    et al.
    Uppsala University, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bjurberg, M.
    Skånes University of Sjukhus, Sweden; Lund University, Sweden.
    Borgfeldt, C.
    Lund University, Sweden.
    Dahm-Kahler, P.
    University of Gothenburg, Sweden.
    Falconer, H.
    Karolinska Institute, Sweden.
    Holmberg, E.
    Sahlgrens University Hospital, Sweden; Gothenburg University, Sweden.
    Staf, C.
    Sahlgrens University Hospital, Sweden.
    Tholander, B.
    Uppsala University Hospital, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden.
    Rosenberg, Per
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Högberg, T.
    Lund University, Sweden.
    Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register studyOn behalf of the Swedish Gynecological Cancer Group2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 12, p. 2693-2700Article in journal (Refereed)
    Abstract [en]

    The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI50% (risk ratio [RR]=4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not. Whats new? Whether lymphadenectomy is beneficial for women with endometrial cancer remains uncertain. Moreover, additional studies are needed to explore factors that reliably predict lymph node metastasis (LNM). Here, multiple factors, including tumor histology, grade of differentiation and DNA aneuploidy, were evaluated for associations with LNM risk in women with endometrial cancer and verified lymph node status. Most significantly, deep myometrial invasion in tumors increased LNM risk fourfold, whereas DNA ploidy had essentially no impact on LNM risk. The findings confirm the predictive relevance of myometrial invasion, histology and grade reported in previous single-center and multicenter studies.

  • 23.
    Sun, Xiao-Feng
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Zhang, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Heat shock protein 72/73 in relation to cytoplasmic p53 expression and prognosis in colorectal adenocarcinomas1997In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 74, no 6, p. 600-604Article in journal (Refereed)
    Abstract [en]

    Heat shock proteins (hsp) are molecular chaperones that are increased by various environmental and patho-physiological stimuli. Hsp can bind to mutant/wild-type p53 in tumors and, consequently, could not only regulate p53 accumulation or localization but also modulate its biological effects on cells. However, there is little information available on the significance of hsp expression in colorectal cancer. The aim of our study was to investigate the relationship of hsp to p53 expression, clinico-pathological factors and prognosis in a series of 256 patients with colorectal adenocarcinomas, using immuno-histochemistry. Seventy-five cases exhibited hsp expression in the cytoplasm, with 11 presenting both cytoplasmic and nuclear staining. Hsp expression was related positively to cytoplasmic p53 expression but not to nuclear p53 expression. In the subgroup of rectal tumors, hsp over-expression appeared to predict unfavorable survival, though its prognostic value diminished using multivariate analysis. There were no significant relationships of hsp with patient sex or age, tumor site, Duke's stage, growth pattern or differentiation.

  • 24.
    Trager, Catarina
    et al.
    Karolinska University Hospital, Sweden.
    Vernby, Asa
    Karolinska University Hospital, Sweden.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ora, Ingrid
    Lund University Hospital, Sweden.
    Kogner, Per
    Karolinska University Hospital, Sweden.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are specific for neuroblastoma minimal disease and predicts outcome for children with high-risk disease when measured at diagnosis2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, no 12, p. 2849-2855Article in journal (Refereed)
    Abstract [en]

    Several transcripts have been claimed to be clinically valuable for detecting minimal disease in neuroblastoma, but they have not been prospectively compared in a standardized manner. Tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and GD2 synthase (GD2S) mRNAs were analyzed in 554 blood (PB) and bone marrow (BM) samples from 58 children with neuroblastoma. Samples from 44 children with other diseases served as controls. High transcript concentrations of TH, GD2S or DDC in PB or BM at diagnosis were associated with poor prognosis. TH in BM above median indicated worse outcome for a homogenous cohort with high-risk neuroblastoma (survival probability 91% for TH below median versus 33% for TH above median, p = 0.009). The number of children with localized neuroblastoma with increased results in PB did not differ between the three transcripts. In these children, all without morphologically detectable neuroblastoma in BM, the number of patients with elevated GD2S in BM at diagnosis was significantly higher than for the other transcripts (10/16 elevated, P = 0.012). GD2S was elevated in PB from 10/28 controls without neuroblastoma compared to 1/28 for TH and DDC (p < 0.001). In BM from these children GD2S was significantly elevated. We conclude that high expression of TH and DDC both in Ill and BM corresponds to metastatic neuroblastoma at diagnosis, residual disease, and poor outcome. Children with high-risk neuroblastoma and low levels of TH in BM at diagnosis may be cured by current therapy. GD2S is less specific than TH and DDC mRNA for neuroblastoma detection in PB and BM.

  • 25.
    Utjes, Deborah
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regional Board, Research and Development Unit.
    Lapins, Jan
    Karolinska University Hospital, Sweden.
    Eriksson, Hanna
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Reduced disease-specific survival following a diagnosis of multiple primary cutaneous malignant melanomas-a nationwide, population-based study2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 11, p. 2243-2252Article in journal (Refereed)
    Abstract [en]

    Outcome data comparing patients with multiple primary invasive cutaneous malignant melanomas (MPMs) to single primary invasive cutaneous malignant melanomas (SPMs) show conflicting results. We have analyzed differences in disease-specific survival between these patients in a nationwide population-based setting. From the Swedish Melanoma Register, 27,235 patients were identified with a first invasive cutaneous malignant melanoma (CMM) between 1990 and 2007, followed-up through 2013. Of these, 700 patients developed MPMs. Cox proportional hazard regression was used for adjusted cause-specific hazard ratios (HRs). An interval of amp;lt;= 5 years between CMM diagnoses was significantly correlated to a decreased CMM-specific survival in Stage I-II MPM-vs. SPM-patients (HR 1.32; 95% CI 1.04-1.67; p=0.02). MPM-patients with longer time interval between diagnoses experienced similar risk of CMM-death as SPM-patients. The risk of CMM-death increased by almost 50% above the expected outcome according to stage of the index CMM by the diagnosis of a second CMM (HR 1.48; 95% CI 1.19-1.85; p amp;lt; 0.001). MPM vs. SPM-patients had a worse outcome (HR 1.38; 95% CI 1.05-1.83; p=0.001). This emphasizes the importance of prevention efforts in SPM-patients to decrease the risk of subsequent CMMs and has implications for more vigilant follow-up in MPM-patients.

  • 26.
    Wang, H
    et al.
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Bjurstam, N
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Bjorndal, H
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Braaten, A
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Eriksen, L
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Skaane, P
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Vitak, B
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Hofvind, S
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Thoresen, SO
    Canc Registry Norway, Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Univ Bergen, Haukeland Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Univ Oslo, Ulleval Hosp, Oslo, Norway Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Interval cancers in breast cancer screening: mistakes by the radiolgists or a special group of cancers?2002In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, p. 32-32Conference paper (Other academic)
  • 27.
    Wang, HG
    et al.
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Bjurstam, N
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Bjorndal, H
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Braaten, A
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Eriksen, L
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Skaane, P
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Vitak, B
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Hofvind, S
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Thoresen, SO
    Canc Registry Norway, N-0310 Oslo, Norway Univ Tromso Hosp, N-9012 Tromso, Norway Norwegian Radium Hosp, Oslo, Norway Haukeland Univ Hosp, N-5021 Bergen, Norway Cent Hosp Rogaland Cty, Stavanger, Norway Ulleval Univ Hosp, Oslo, Norway Linkoping Univ Hosp, Linkoping, Sweden.
    Interval cancers in the Norwegian Breast Cancer Screening Program: Frequency, characteristics and use of HRT2001In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 94, no 4, p. 594-598Article in journal (Refereed)
    Abstract [en]

    Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2-year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening-detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9-20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43-0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening-detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus. (C) 2001 Wiley-Liss, Inc.

  • 28.
    Wangsa, Darawalee
    et al.
    NCI, MD 20892 USA; Karolinska University Hospital, Sweden.
    Akhter Chowdhury, Salim
    Carnegie Mellon University, PA 15213 USA; Carnegie Mellon University, PA 15213 USA.
    Ryott, Michael
    Sophiahemmet Hospital, Sweden.
    Michael Gertz, E.
    NIH, MD 20892 USA.
    Elmberger, Goran
    Örebro University Hospital, Sweden.
    Auer, Gert
    Karolinska University Hospital, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Karolinska University Hospital, Sweden.
    Kueffer, Stefan
    University of Medical Centre Gottingen, Germany.
    Stroebel, Philipp
    University of Medical Centre Gottingen, Germany.
    Schaeffer, Alejandro A.
    NIH, MD 20892 USA.
    Schwartz, Russell
    Carnegie Mellon University, PA 15213 USA; Carnegie Mellon University, PA 15213 USA.
    Munck-Wikland, Eva
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Ried, Thomas
    NCI, MD 20892 USA.
    Heselmeyer-Haddad, Kerstin
    NCI, MD 20892 USA.
    Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 1, p. 98-109Article in journal (Refereed)
    Abstract [en]

    Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty-five OTSCC patients (Stage I, n=15; Stage II, n=30; Stage III, n=7; Stage IV, n=13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non-smoking habits, while smokers in this cohort had low-level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease-free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress. Whats new? Oral tongue squamous cell carcinoma (OTSCC) is a rare head and neck cancer that typically is asymptomatic in early stages. Hence, in order to improve prognosis in OTSCC, predictive biomarkers that are independent of tumor stage must be identified. Here, using four fluorescence in situ hybridization (FISH) gene probes and the software FISHtrees, phylogenetic tree models of tumor progression in OTSCC patients were constructed. Analyses of the models showed that the more diverse the changes within the four marker genes, the worse the outcome in OTSCC. The markers predicted survival independent of smoking behavior and tumor stage.

  • 29.
    Zhang, Hong
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Ahmadi, Ahmad
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Arbman, G
    Zdolsek, J
    Carstensen, J
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Söderkvist, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Glutathione S-transferase T1 and M1 genotypes in normal mucosa, transitional mucosa and colorectal adenocarcinom.1999In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 84, p. 135-138Article in journal (Refereed)
  • 30. Zhou, Xiao-Lei
    et al.
    Eriksson, Ulrika
    Werelius, Barbro
    Kressner, Ulf
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Lindblom, Annika
    Definition of candidate low risk APC alleles in a Swedish population2004In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 110, no 4, p. 550-557Article in journal (Refereed)
    Abstract [en]

    Many families experience an apparently inherited increased risk of colorectal cancer (CRC) similar to the known syndromes familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). Besides these high-risk syndromes, approximately 10% of all CRC cases come from families with 2 affected 1st-degree relatives, and even 1st-degree relatives to a single case of CRC are at increased risk. Risk subjects from these families frequently show polyps at colonoscopy, which suggests the APC gene as a good candidate susceptibility gene for these attenuated polypotic syndromes. We used the sensitive DHPLC technique to search for possible predisposing germline mutations in the entire APC gene in 91 risk subjects from these high- and low-risk syndromes with unknown predisposing genes. Most exons were also screened for mutations in 96 normal controls and 96 colorectal cancer cases. In our study we probably have identified the most common APC variants in a Swedish population. Among 30 germline variants identified, 1 clearly pathogenic nonsense mutation and 11 putative pathogenic variants (10 missense and one 3′ UTR) were found in 20 index patients (22%). Twelve silent as well as 5 intronic variants were considered nonpathogenic. Two of the missense variants found here, E1317Q and D1822V, have previously been related to a difference in risk of colorectal cancer. One variant, 8636C>A, located within the 3′ UTR region of the APC gene, was suggested to constitute an additional low risk allele with a similar relative risk as the Jewish 11307K mutation (OR = 1.8, 9S% CI, 0.96-3.40). The question of whether all the other variants confer an increased colorectal cancer risk warrants future large association studies. © 2004 Wiley-Liss, Inc.

1 - 30 of 30
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf