| 1. |
- Andersen, Niels S., et al.
(författare)
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Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
- 2009
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
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| 2. |
- Andersson, Anne, 1966-, et al.
(författare)
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Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma
- 2008
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 98:5, s. 1001-1005
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Tidskriftsartikel (refereegranskat)abstract
- This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ≥2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme.
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| 3. |
- Andersson, Anne, 1966-, et al.
(författare)
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Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors : retrospective cohort analyses and a concept for prospective intervention
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:8, s. 1914-1917
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first-degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in-patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow-up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on-going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept.
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| 4. |
- Andersson, Ulrika, et al.
(författare)
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Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas
- 2004
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 108:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of epidermal growth factor receptor (EGFR, ErbB1) correlates with enhanced malignant potential of many human tumor types including glioblastoma multiforme. The significance of EGFR expression in meningiomas is, however, unclear. Reports regarding the other EGFR family members, ErbB2-4, in brain tumors are sparse. In this study, the expression of the EGFR family members was analyzed in relation to various parameters for the clinical importance of these receptors in 44 gliomas and 26 meningiomas. In gliomas, quantitative real-time reverse transcription (RT)-PCR revealed the highest EGFR mRNA expression in high-grade gliomas, while ErbB2 and ErbB3 mRNA were detected only in a few high-grade gliomas. In contrast, ErbB4 expression was most pronounced in low-grade gliomas. Immunohistochemistry showed significantly higher EGFR protein expression in high-grade gliomas compared to low-grade gliomas (P= 0.004). ErbB2 protein expression was mainly seen in high-grade gliomas. ErbB3 protein expression was low in all gliomas analyzed. ErbB4 protein expression was significantly higher in low-grade gliomas than in high-grade gliomas (P= 0.007). In meningiomas, quantitative real-time RT-PCR revealed expression of EGFR, ErbB2, and ErbB4 mRNA in the majority of the tumors. ErbB3 was detected in only one of the meningiomas analyzed. Immunohistochemistry demonstrated high ErbB2 protein expression in meningiomas. An intriguing observation in astrocytomas and oligodendrogliomas grade II, was a significantly decreased overall survival for patients with high EGFR protein expression (P= 0.04). The high ErbB4 expression in low-grade compared to high-grade gliomas might suggest that ErbB4 acts as a suppressor of malignant transformation in brain tumors, which is in line with previous studies in other tumor types.
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| 5. |
- Andersson, Ulrika, 1963-
(författare)
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Experimental studies in brain tumours : with special regard to multidrug resistance and the ErbB-family
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Primary brain tumours, and especially the most common form malignant gliomas, usually display a pronounced resistance to other treatment modalities when surgery fails to cure. Growth factors, such as EGF and its receptor, frequently amplified and overexpressed in malignant gliomas, and factors associated with multidrug resistance have been suggested to at least partially explain the poor outcome. The aim of this thesis was to characterise factors in primary brain tumours associated with the development of resistance with focus on the epidermal growth factor receptor (ErbB) family, and multidrug resistance (MDR). Influences of irradiation on the expression and activity of P-glycoprotein (Pgp) in malignant gliomas was evaluated. The effects showed that irradiation increased the efflux activity of Pgp in rat brain vascular endothelial cells, but not in glioma cells. In the intracranial BT4C glioma model, Pgp was detected in the capillary endothelium in the tumour tissue but not in glioma cells. Expression of several factors coupled to MDR (Pgp, MRP1, LRP, and MGMT) in primary brain tumours were analysed and correlated to clinical data. In gliomas, Pgp and MRP1 were predominantly observed in capillary endothelium and in scattered tumour cells, whereas LRP occurred only in tumour cells. In meningiomas, expression of the analysed markers was demonstrated in the capillary endothelium, with a higher expression of Pgp and MRP1 in transitional compared to meningothelial meningiomas. A pronounced expression of MGMT was found independently of the histopathological grade or tumour type. Survival analysis indicated a shorter overall survival for patients suffering from low-grade gliomas with high expression of Pgp. To explore the importance of the epidermal growth factor receptor (EGFR), expression levels of the family members (EGFR, ErbB2-4) were analysed and their relations to various clinical parameters were evaluated in gliomas and meningiomas. In gliomas, the highest EGFR expression was observed in high-grade tumours, while ErbB4 expression was most pronounced in low-grade tumours. In meningiomas, expression of EGFR, ErbB2, and ErbB4 was observed in the majority of the tumours. An intriguing observation in low-grade gliomas was a significantly decreased overall survival for patients with high EGFR protein expression. The effects of different time schedules for administration of the selective EGFR inhibitor ZD1839 in relation to irradiation of glioma cells were analysed. The analyses showed a heterogeneity in the cytotoxic effects of ZD1839 between cell lines, and it was obvious that some of the cell lines showed sensitivity to ZD1839 despite no or low expression of EGFR. The study also demonstrated the importance of timing of ZD1839 administration when this agent is combined with irradiation. In conclusion, in order to enhance the efficacy of radiotherapy by various drugs in malignant gliomas it may be essential to inhibit drug efflux activity in endothelial cells and to deliver drugs in an optimal timing in relation to radiotherapy. The heterogeneity in expression of drug resistance markers, as well as the ErbB family reflects the complexity in classification of primary brain tumours, and indicates that subgroups of patients with low-grade gliomas expressing Pgp and EGFR might benefit from more aggressive and individualised treatment.
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| 6. |
- Andersson, Ulrika, et al.
(författare)
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Genetic variants in association studies : review of strengths and weaknesses in study design and current knowledge of impact on cancer risk
- 2009
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:7, s. 948-954
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Tidskriftsartikel (refereegranskat)abstract
- Sequencing of the human genome has recently been completed and mapping of the complete genomic variation is ongoing. During the last decade there has been a huge expansion of studies of genetic variants, both with respect to association studies of disease risk and for studies of genetic factors of prognosis and treatments response, i.e., pharmacogenomics. The use of genetics to predict a patient's risk of disease or treatment response is one step toward an improved personalised prevention and screening modality for the prevention of cancer and treatment selection. The technology and statistical methods for completing whole genome tagging of variants and genome wide association studies has developed rapidly over the last decade. After identifying the genetic loci with the strongest, statistical associations with disease risk, future studies will need to further characterise the genotype-phenotype relationship to provide a biological basis for prevention and treatment decisions according to genetic profile. This review discusses some of the general issues and problems of study design; we also discuss challenges in conducting valid association studies in rare cancers such as paediatric brain tumours, where there is support for genetic susceptibility but difficulties in assembling large sample sizes. The clinical interpretation and implementation of genetic association studies with respect to disease risk and treatment is not yet well defined and remains an important area of future research.
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| 7. |
- Andersson, Ulrika, et al.
(författare)
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Heterogeneity in the expression of markers for drug resistance in brain tumors
- 2004
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Ingår i: Clinical Neuropathology. - 0722-5091. ; 23:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Brain tumors, in general, display a multidrug-resistant phenotype. This study evaluated the immunohistochemical expression and distribution of P-glycoprotein (Pgp), multidrug resistance protein (MRP1), lung resistance protein (LRP) and O6 methylguanine-DNA methyltransferase (MGMT) in low- and high-grade astrocytoma, oligodendroglioma and in different subgroups of meningioma. The results revealed a marked heterogeneity in the expression and distribution among the analyzed tumors. In astrocytoma and oligodendroglioma, Pgp and MRP1 were observed in the capillary endothelium and in scattered tumor cells, whereas LRP occurred only in tumor cells. A pronounced expression of MGMT was found independent of the histopathological grade. An enhanced expression of MRP1 and LRP in astrocytoma and oligodendroglioma were more often evident in older patients (> 50 years). Survival analysis suggested a markedly decreased overall survival for patients suffering from low-grade glioma overexpressing Pgp. In meningioma, a heterogeneous expression of Pgp, MRP1, LRP and MGMT was seen with the most prominent staining localized to the capillary endothelium. Pgp was significantly more often overexpressed (p < 0.05) in transitional compared to meningothelial meningioma. The marked heterogeneity in the expression suggests that analysis of these factors can be of importance in the selection of individualized chemotherapy, regardless of tumor type.
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| 8. |
- Andersson, Ulrika, et al.
(författare)
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MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome.
- 2009
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 125:4, s. 968-972
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Tidskriftsartikel (refereegranskat)abstract
- The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival was analysed using Kaplan-Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype was not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus the LL was nonsignificantly increased HR 1.46 (0.81-2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR was 2.10 (1.41-3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations.
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| 9. |
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| 10. |
- Berntsson, Shala, et al.
(författare)
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Tumor-associated epilepsy and glioma : are there common genetic pathways?
- 2009
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:7, s. 955-963
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Forskningsöversikt (refereegranskat)abstract
- Background. Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors. Material and methods. No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma. Results. This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.
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| 11. |
- Bethke, Lara, et al.
(författare)
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CASP8 D302H and meningioma risk : an analysis of five case-control series
- 2009
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Ingår i: Cancer Letters. - Clare : Elsevier. - 0304-3835 .- 1872-7980. ; 273:2, s. 312-315
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Tidskriftsartikel (refereegranskat)abstract
- Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breast cancer. We tested the hypothesis that the CASP8 polymorphism D302H may influence risk of meningioma through analysis of five independent series of case patients and controls (n=631 and 637, respectively). Carrier status for 302H was not associated with a statistically significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it unlikely that this variant contributes to the inherited risk of meningioma.
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| 12. |
- Bethke, Lara, et al.
(författare)
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Comprehensive analysis of DNA repair gene variants and risk of meningioma
- 2008
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:4, s. 270-276
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Tidskriftsartikel (refereegranskat)abstract
- Background: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility.Methods: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case–control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided.Results: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1–interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; Ptrend = 8.95 × 10−6; P = .009 after adjusting for multiple testing).Conclusions: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.
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| 13. |
- Bethke, Lara, et al.
(författare)
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Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma
- 2008
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 17:6, s. 800-805
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Tidskriftsartikel (refereegranskat)abstract
- Much of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizing radiation led us to examine whether variants in the DNA repair genes contribute to disease susceptibility. We evaluated 1127 haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388 putative functional SNPs to capture most of the common variation in 136 DNA repair genes, in five unique case–control series from four different countries (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at the 1% significance level. The highest association observed across the five independent case–control datasets involved rs243356, which maps to intron 3 of CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14–1.54; P = 0.0002; false-positive report probability = 0.055, based on a prior probability of 0.01). Our results provide additional support for the hypothesis that low penetrance variants contribute to the risk of developing glioma and suggest that a genetic variant located in or around the CHAF1A gene contributes to disease risk.
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| 14. |
- Bethke, Lara, et al.
(författare)
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Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:5, s. 1195-1202
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Tidskriftsartikel (refereegranskat)abstract
- Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.
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| 15. |
- Bethke, Lara, et al.
(författare)
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The Common D302H Variant of CASP8 Is Associated with Risk of Glioma
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:4, s. 987-989
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Tidskriftsartikel (refereegranskat)abstract
- Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor.
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| 16. |
- Bondy, M L, et al.
(författare)
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Brain tumor epidemiology : Consensus from the Brain Tumor Epidemiology Consortium
- 2008
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 113, s. 1953-1968
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings, possibly because of small sample sizes in individual studies and differences between studies in patients, tumor types, and methods of classification. Individual studies generally have lacked samples of sufficient size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in Promoting understudied groups, such as pediatric brain tumors; the etiology of rare glioma subtypes, such as oligodendroglioma; and meningioma, which, although it is not uncommon, has only recently, been registered systematically in the United States. There also is a pressing need for more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. In this report, BTEC epidemiologists reviewed the groups Consensus oil the Current state of scientific findings, and they present a consensus oil research priorities to identify which important areas the science should move to address.
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| 17. |
- Britton, Julie A, et al.
(författare)
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Anthropometric characteristics and non-Hodgkin's lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
- 2008
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 93:11, s. 1666-1677
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The incidences of non-Hodgkin's lymphoma and multiple myeloma are increasing steadily. It has been hypothesized that this may be due, in part, to the parallel rising prevalence of obesity. It is biologically plausible that anthropometric characteristics can infuence the risk of non-Hodgkin's lymphoma and multiple myeloma.DESIGN AND METHODS:In the context of the European Prospective Investigation into Cancer and Nutrition (EPIC), anthropometric characteristics were assessed in 371,983 cancer-free individuals at baseline. During the 8.5 years of follow-up, 1,219 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma occurred in 609 men and 610 women. Gender-specific proportional hazards models were used to estimate relative risks and 95% confidence intervals (95% CI) of development of non-Hodgkin's lymphoma and multiple myeloma in relation to the anthropometric characteristics.RESULTS:Height was associated with overall non-Hodgkin's lymphoma and multiple myeloma in women (RR 1.50, 95% CI 1.14-1.98) for highest versus lowest quartile; p-trend < 0.01) but not in men. Neither obesity (weight and body mass index) nor abdominal fat (waist-to-hip ratio, waist or hip circumference) measures were positively associated with overall non-Hodgkin's lymphoma and multiple myeloma. Relative risks for highest versus lowest body mass index quartile were 1.09 (95% CI 0.85-1.38) and 0.92 (95% CI 0.71-1.19) for men and women, respectively. Women in the upper body mass index quartile were at greater risk of diffuse large B-cell lymphoma (RR 2.18, 95% CI 1.05-4.53) and taller women had an elevated risk of follicular lymphoma (RR 1.25, 95% CI 0.59-2.62). Among men, height and body mass index were non-significantly, positively related to follicular lymphoma. Multiple myeloma risk alone was elevated for taller women (RR 2.34, 95% CI 1.29-4.21) and heavier men (RR 1.77, 95% CI 1.02-3.05).CONCLUSIONS:The EPIC analyses support an association between height and overall non-Hodgkin's lymphoma and multiple myeloma among women and suggest heterogeneous subtype associations. This is one of the first prospective studies focusing on central adiposity and non-Hodgkin's lymphoma subtypes.
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| 18. |
- Davis, Faith G, et al.
(författare)
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Issues of diagnostic review in brain tumor studies : from the brain tumor epidemiology consortium
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 17:3, s. 484-489
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologists routinely conduct centralized single pathology reviews to minimize interobserver diagnostic variability, but this practice does not facilitate the combination of studies across geographic regions and institutions where diagnostic practices differ. A meeting of neuropathologists and epidemiologists focused on brain tumor classification issues in the context of protocol needs for consortial studies (http://epi.grants.cancer.gov/btec/). It resulted in recommendations relevant to brain tumors and possibly other rare disease studies. Two categories of brain tumors have enough general agreement over time, across regions, and between individual pathologists that one can consider using existing diagnostic data without further review: glioblastomas and meningiomas (as long as uniform guidelines such as those provided by the WHO are used). Prospective studies of these tumors benefit from collection of pathology reports, at a minimum recording the pathology department and classification system used in the diagnosis. Other brain tumors, such as oligodendroglioma, are less distinct and require careful histopathologic review for consistent classification across study centers. Epidemiologic study protocols must consider the study specific aims, diagnostic changes that have taken place over time, and other issues unique to the type(s) of tumor being studied. As diagnostic changes are being made rapidly, there are no readily available answers on disease classification issues. It is essential that epidemiologists and neuropathologists collaborate to develop appropriate study designs and protocols for specific hypothesis and populations.
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| 19. |
- Davis, Faith, et al.
(författare)
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Second primary tumors following a diagnosis of meningioma in Sweden, 1958-1997.
- 2007
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 29:1-2, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- This study quantifies the risk of second primary tumors following a diagnosis of meningioma. 12,012 meningiomas and 926 second primary cancers were identified (ICD7, path code 461) between1958 and 1997 using Swedish Cancer Registry data. Standardized incidence ratios (SIRs) and exact 95% confidence intervals (CIs) were calculated. An elevated risk of any second primary cancer diagnosis (SIR = 1.2, 95% CI = 1.1–1.3) was observed. Elevated and statistically significant SIRs were observed for renal cancer (SIR = 1.6), melanoma (SIR = 1.7), thyroid cancer (SIR = 2.6) and brain tumors (SIR = 2.6). A consistent pattern of risk over time supports the evaluation of common risk factor profiles for renal, melanoma and thyroid cancers. Radiation exposures increase the risk of these rare tumors, so quantifying the cumulative and shared effects of environmental and treatment exposures is of further interest.
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| 20. |
- Hermann, Silke, et al.
(författare)
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Level of education and the risk of lymphoma in the European prospective investigation into cancer and nutrition
- 2010
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 1432-1335 .- 0171-5216. ; 136:1, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- Lymphomas belong to the few cancer sites with increasing incidence over past decades, and only a few risk factors have been established. We explored the association between education and the incidence of lymphoma in the prospective EPIC study. Within 3,567,410 person-years of follow-up, 1,319 lymphoma cases [1,253 non-Hodgkin lymphomas (NHL) and 66 Hodgkin lymphomas (HL)] were identified. Cox proportional hazard regression was used to examine the association between highest educational level (primary school or less, technical/professional school, secondary school, university) and lymphoma risk. Overall, no consistent associations between educational level and lymphoma risk were observed; however, associations were found for sub-groups of the cohort. We observed a higher risk of B-NHL (HR = 1.31, 95% CI = 1.02-1.68; n = 583) in women with the highest education level (university) but not in men. Concerning sub-classes of B-NHL, a positive association between education and risk of B cell chronic lymphatic leukaemia (BCLL) was observed only in women. In both genders, the risk of diffuse large B cell lymphoma (DLBCL) was significantly lower for subjects with university degree (HR = 0.46, 95% CI = 0.27-0.79) versus lowest educational level. No association was found for HL. We could not confirm an overall consistent association of education and risk of HL or NHL in this large prospective study; although, education was positively related to the incidence of BCLL and B-NHL (in women) but inversely to incidence of DLBCL. Due to limited number of cases in sub-classes and the large number of comparisons, the possibility of chance findings can not be excluded.
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| 21. |
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| 22. |
- Kiuru, Anne, et al.
(författare)
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XRCC1 and XRCC3 variants and risk of glioma and meningioma
- 2008
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Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 88, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and modifying cancer susceptibility have been described. We evaluated the association of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3) DNA repair genes with the risk of brain tumors. The Caucasian study population consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases, and 1,560 controls in a prospective population-based case-control study conducted in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly associated with the risk of brain tumors. The highest odds ratios (ORs) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97-1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34; 95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors: Among others, carriers of both homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26-8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no significant association with brain tumors was found for any of the polymorphisms, when examined one by one. Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.
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| 23. |
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| 24. |
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| 25. |
- Ljuslinder, Ingrid, 1968-, et al.
(författare)
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ErbB 1-4 expression alterations in primary colorectal cancers and their corresponding metastases
- 2009
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:5, s. 1489-1494
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: EGFR (epidermal growth factor receptor) targeted therapies are important new tools in colorectal cancer treatment. EGFR analysis of the primary tumour was previously recommended to identify patients who will benefit from the EGFR targeted therapy. Previous studies have displayed diverging results regarding the expression of EGFR in the primary tumour compared to the metastases. The present study was performed to investigate whether EGFR and ErbB2-4 expression differed between 64 primary tumours and their corresponding metastases. PATIENTS AND METHODS: EGFR and ErbB2-4 expression were analysed in the primary tumour and in the corresponding metastases using immunohistochemistry (IHC). RESULTS: In 49/64 samples (76%), the primary tumours were EGFR positive; in 33% (16/49) of EGFR positive samples, the tumours lost the EGFR expression in the metastasis compared to the primary tumour. From the primary tumours, 15/64 (23%) were negative and 5 of these (33%) developed EGFR expression in the metastasis. ErbB2, ErbB3, and ErbB4 expression was evident in 54%, 67%, and 81%, respectively. There was no significant difference between ErbB2, ErbB3, and ErbB4 expression in primary tumours and metastases. The co-expression of the ErbB family members was also analysed, with a significant increase of ErbB3/ErbB4 co-expression in late stage tumours. CONCLUSION: The EGFR expression was lost in 33% of metastasising primary colorectal cancer tumours, a finding that agrees with at least one previous study. Thus, the present results clearly implicate the need for EGFR analysis of both the primary tumour and metastases to accurately determine EGFR status when considering the use of EGFR targeted therapies.
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| 26. |
- Ljuslinder, Ingrid, 1968-, et al.
(författare)
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Increased copy number at 3p14 in breast cancer
- 2005
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7:5, s. R719-R727
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Tidskriftsartikel (refereegranskat)
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| 27. |
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| 28. |
- Ljuslinder, Ingrid, 1968-, et al.
(författare)
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LRIG1 expression in colorectal cancer
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:8, s. 1118-1122
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Tidskriftsartikel (refereegranskat)
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| 29. |
- Ljuslinder, Ingrid, 1968-
(författare)
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Studies of LRIG1 and the ERBB receptor family in breast and colorectal cancer
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The LRIG1 gene (leucine-rich repeats and immunoglobulin like domains-1) at chromosome 3p14 is a proposed tumour suppressor gene whose gene product negatively regulates various receptor tyrosine kinases. This function has been the basis for classifying LRIG1 as a potential tumour suppressor gene (TSG). The ERBB receptor family is important in malignant cellular functions such as proliferation, survival, adhesion, migration and differentiation. In breast cancer, amplification of the ERBB2 proto-oncogene is an important negative prognostic factor. The epidermal growth factor receptor (EGFR/ERBB1), is expressed in colorectal cancer and has been correlated to a worse prognosis. Until recently, immunohistochemical analysis of EGFR expression was used to select patients suitable for treatment with EGFR targeted antibodies. This thesis characterizes LRIG1 in breast and colorectal cancer to gain further knowledge of the gene and its expression. Also, the EGFR expression in metastases and the invasive margin of colorectal cancers was investigated to correlate changes to clinical factors. Breast cancer samples and matched normal tissues were evaluated for LRIG1 and the ERBB receptors at gene, RNA and protein levels. An increase in copy number of the LRIG1 gene was evident. Also, increased LRIG1 copy number was associated with high levels of ERBB2 mRNA. Another set of breast cancer tumours were analysed for LRIG1 by FISH analysis. The results were coherent with the previous results. To further analyze the correlation to ERBB2, tumours with LRIG1 increased copy number were analysed for ERBB2. The data showed that 89% of tumours with increased LRIG1 copy number were either ERBB2 amplified or had an increased copy number of ERBB2. To investigate LRIG1 and the EGFR in colorectal cancer, the gene and protein expression was analysed by several methods in tumours and corresponding normal tissues. There were no significant changes at gene level found, but at the protein level, both over- and under expression were seen. No evident correlation between LRIG1 and EGFR expression was detected. The ERBB receptor family expression in colorectal cancer tumours and corresponding metastases was investigated to explore if the expression was altered in the metastatic lesion. The results showed that the EGFR expression was lost in the corresponding metastases in 33% of the tumours and that the same percentage of tumours gained expression in the metastases. Co-expression of the ERBB family members was also analysed; there was a significant increase of ERBB3/ERBB4 co-expression in late stage tumours. EGFR expression at the invasive margin of colorectal cancers was analysed to clarify whether expression correlated to the patient’s prognosis. Significant correlation to survival and the presence of budding was seen. In conclusion, 34% of the breast cancer tumours studied had an increased copy number of LRIG1 with a significant co-incidental increase in ERBB2 copy number. This raises the question of a functional correlation between LRIG1 and ERBB2, a finding that might be of clinical importance. The studies of EGFR and the ERBB receptors in colorectal cancer reflect the heterogeneity of EGFR expression in tumours. In addition, these findings suggest that survival of the patients correlates to an increasing EGFR expression at the invasive margin.
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| 30. |
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| 31. |
- Malmer, Beatrice, et al.
(författare)
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GLIOGENE an International Consortium to Understand Familial Glioma
- 2007
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 16:9, s. 1730-1734
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Tidskriftsartikel (refereegranskat)
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| 32. |
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| 33. |
- Malmer, Beatrice, et al.
(författare)
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p53 Genotypes and risk of glioma and meningioma
- 2005
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1055-9965. ; 14:9, s. 2220-2223
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Tidskriftsartikel (refereegranskat)
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| 34. |
- McCarthy, Bridget J, et al.
(författare)
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A Case for the Worldwide Collection of Primary Benign Brain Tumors.
- 2009
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 33:3, s. 268-275
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Tidskriftsartikel (refereegranskat)abstract
- Background: Incidence data on malignant tumors are reported by the International Agency for Research on Cancer, with 189,485 new malignant brain tumors globally in 2002. However, collection and reporting of benign brain tumors are not universal. The objective here is to encourage the collection of primary benign brain tumors worldwide. Methods: Worldwide numbers of primary benign brain tumors were estimated through published articles and cancer registry reports presenting directly or indirectly reported benign incidence rates or frequencies for regions or countries. Results: An estimated 186,678 benign brain tumors were diagnosed worldwide in 2002. The estimated numbers of benign brain tumors were higher in females than males (105,918 vs. 80,759). Since many countries do not report primary benign brain tumors, the incidence rate estimates vary significantly by region. Conclusions: This is the first survey to assess worldwide numbers of benign brain tumors. Under-reporting, non-standardized collection, lack of age-adjustment, and other causes of the varying incidence rates must be considered. However, the estimated number of benign brain tumors approximately equals, and could exceed, the number of malignant brain tumors globally. Registration of primary benign brain histologies in different geographical areas and ethnicities could provide clues to the underlying causes of these tumors.
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| 35. |
- Mogren, Ingrid, et al.
(författare)
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Reproductive factors have low impact on the risk of different primary brain tumours in offspring
- 2003
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Ingår i: Neuroepidemiology. - : S. Karger. - 0251-5350 .- 1423-0208. ; 22:4, s. 249-254
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of our study was to investigate whether reproductive factors influence the risk of primary brain tumours (PBT) in offspring. Methods: Data on all deliveries in two Swedish counties from 1955 to 1990 were extracted from two birth registries. The follow-up period closed at the end of 1994, with subjects followed up to early middle age. Incidence rates of malignancy for 1958-1994 were obtained from the Swedish Cancer Registry. Standardised incidence ratios (SIR) and relative risks were calculated for astrocytomas, primitive neuroectodermal tumour, ependymoma and meningiomas in offspring. Results: Few associations were detected. High birth weight indicated an increased risk for astrocytomas grade I and II for all primary brain tumours, and the risk was close to significance for astrocytomas grade I-II (SIR = 3.64; CI = 0.98-9.31). For children under 15 years of age the risk for astrocytomas grade I and II was further increased (SIR = 4.44; Cl = 1.19-11.38). Conclusions:A consistent pattern of non-association indicated a low impact of intrauterine environment on the future development of primary brain tumours in offspring up to early middle age.
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| 36. |
- Neasham, David, et al.
(författare)
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Occupation and risk of lymphoma : a multicentre prospective cohort study (EPIC)
- 2011
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 68:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.
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| 37. |
- Osorio, A., et al.
(författare)
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Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2 (CIMBA)
- 2009
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 101:12, s. 2048-2054
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Tidskriftsartikel (refereegranskat)abstract
- Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Shete, Sanjay, et al.
(författare)
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Genome-wide association study identifies five susceptibility loci for glioma.
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:8, s. 899-904
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Tidskriftsartikel (refereegranskat)abstract
- To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Thellenberg Karlsson, Camilla, 1972-
(författare)
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Prostate cancer : epidemiological studies of risk factors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In spite of the fact that prostate cancer is the most common male cancer in both Sweden and many other countries in the developed world, little is known of risk factors and predisposing conditions. The only well recognized risk factors are age, race and familial aggregation. More knowledge about risk factors could lead to better preventive measures together with better treatments. One way to evaluate this is to study second primary cancers; the connection between two different cancers can give valuable insight in etiology or clues to shared risk factors. This thesis aims at evaluating risk factors for prostate cancer. We constructed a cohort of 135,713 men diagnosed with prostate cancer and reported to the Swedish Cancer Registry 1958-1996. The cohort was followed for second primary cancers and a doubled risk of male breast cancer was found. We also noted increased risks for small intestine cancers and melanoma. As a follow-up on the increased risk of male breast cancer, we performed a nested case – control study. Included cases were men with first prostate and then breast cancer (n = 41) matched to men with only prostate cancer (n =81). For these men, we collected medical records and extracted data regarding treatment. Furthermore, all men diagnosed with both prostate and breast cancer irrespective which came first (n = 83) were used as probands. To both these sets of cases with breast and prostate cancer, we identified first degree relatives and grandchildren from parish offices throughout Sweden. Linking to the Cancer Registry retrieved all cancer diagnoses amongst relatives. Results from this study show a relation between estrogen treatment of prostate cancer and the risk of developing breast cancer. We also found that a small part of the cases with both cancers appeared in families with inheritance patterns possibly attributed to BRCA2. As estrogen treatment seemed involved in increased risk of breast cancer after prostate cancer, we wanted to investigate the newly discovered Estrogen receptor β and the relation to prostate cancer risk. Previous reports have shown that ERβ acts as a negative regulator of proliferation. ERβ expression occurs mainly in prostatic epithelial cells and the expression gradually diminishes when cancer develops and aggravates. We used a single nucleotide polymorphism (SNP) association study approach to evaluate genetic variation in ERβ as a risk factor for prostate cancer. One SNP, located in the promoter region associated with a small increased risk of prostate cancer whereas variation in the rest of the gene did not. In the last paper, we investigated trans-urethral resection (TURP) of the prostate due to benign prostate hyperplasia (BPH) as a risk factor for later development of prostate cancer. Evidence has gathered that both BPH and prostate cancer are associated to inflammation. By comparing incidence and mortality in a cohort of 7,901 men with the general population there appeared to be an increased risk of prostate cancer but decreased mortality. Analyzing this increased risk further, we conducted a nested case - control study with men extracted from the cohort. Cases had a TURP and later developed prostate cancer and controls just had a TURP. We then evaluated the specimens from TURP regarding extent of inflammation, degree of androgen receptor down regulation and expression of p53, all factors previous associated with prostate cancer. None of these parameters differed between cases and controls and they can therefore not explain the increased risk. Decreased mortality but increased risk might be explained by surveillance bias, which means more medical attention to these patients, resulting in diagnosing clinically non-significant cancers. In summary, our results show a doubled risk of male breast cancer following prostate cancer. A risk that can be attributed to the use of estrogen to treat prostate cancer or to some extent a possible mutation in BRCA2. We also propose that a SNP change in the ERβ promoter confer a small increased risk of prostate cancer. A small risk elevation of prostate cancer following TURP most probable could depend on surveillance bias.
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