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  • 1. Abbas, Sascha
    et al.
    Linseisen, Jakob
    Rohrmann, Sabine
    Chang-Claude, Jenny
    Peeters, Petra H
    Engel, Pierre
    Brustad, Magritt
    Lund, Eiliv
    Skeie, Guri
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Kaaks, Rudolf
    Boeing, Heiner
    Buijsse, Brian
    Adarakis, George
    Ouranos, Vassilis
    Trichopoulou, Antonia
    Masala, Giovanna
    Krogh, Vittorio
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Buckland, Genevieve
    Suárez, Marcial Vicente Argüelles
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Amiano, Pilar
    Manjer, Jonas
    Wirfält, Elisabet
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Bueno-de-Mesquita, H B
    van Duijnhoven, Fränzel J B
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Fedirko, Veronika
    Romieu, Isabelle
    Gallo, Valentina
    Norat, Teresa
    Wark, Petra A
    Riboli, Elio
    Dietary intake of vitamin d and calcium and breast cancer risk in the European prospective investigation into cancer and nutrition2013In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 65, no 2, 178-187 p.Article in journal (Refereed)
    Abstract [en]

    Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk.

  • 2.
    Adamo, Hanibal
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahl Scherdin, Tove
    Egevad, Lars
    Granfors, Torvald
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcomeManuscript (preprint) (Other academic)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.

    In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome. 

  • 3.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergström, Sofia Halin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, e0130076Article in journal (Refereed)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating changes in the tumor-bearing organ, for example growth of the vasculature, an altered extracellular matrix, and influx of inflammatory cells. To investigate this response further, we compared prostate morphology and the gene expression profile of tumor-bearing normal rat prostate tissue (termed tumor-instructed/indicating normal tissue (TINT)) with that of prostate tissue from controls. Dunning rat AT-1 prostate cancer cells were injected into rat prostate and tumors were established after 10 days. As controls we used intact animals, animals injected with heat-killed AT-1 cells or cell culture medium. None of the controls showed morphological TINT-changes. A rat Illumina whole-genome expression array was used to analyze gene expression in AT-1 tumors, TINT, and in medium injected prostate tissue. We identified 423 upregulated genes and 38 downregulated genes (p<0.05, >= 2-fold change) in TINT relative to controls. Quantitative RT-PCR analysis verified key TINT-changes, and they were not detected in controls. Expression of some genes was changed in a manner similar to that in the tumor, whereas other changes were exclusive to TINT. Ontological analysis using GeneGo software showed that the TINT gene expression profile was coupled to processes such as inflammation, immune response, and wounding. Many of the genes whose expression is altered in TINT have well-established roles in tumor biology, and the present findings indicate that they may also function by adapting the surrounding tumor-bearing organ to the needs of the tumor. Even though a minor tumor cell contamination in TINT samples cannot be ruled out, our data suggest that there are tumor-induced changes in gene expression in the normal tumor-bearing organ which can probably not be explained by tumor cell contamination. It is important to validate these changes further, as they could hypothetically serve as novel diagnostic and prognostic markers of prostate cancer.

  • 4.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Strömvall, Kerstin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, e0141601Article in journal (Refereed)
    Abstract [en]

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.

  • 5. Agudo, Antonio
    et al.
    Bonet, Catalina
    Sala, Núria
    Muñoz, Xavier
    Aranda, Núria
    Fonseca-Nunes, Ana
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie Christine
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Grioni, Sara
    Quirós, J Ramón
    Molina, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Chamosa, Saioa
    Allen, Naomi E
    Khaw, Kay-Tee
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Numans, Mattijs E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Kaaks, Rudof
    Canzian, Federico
    Boeing, Heiner
    Meidtner, Karina
    Johansson, Mattias
    Umeå University, Faculty of Medicine. WHO, IARC, Lyon, France.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Manjer, Jonas
    Overvad, Kim
    Tjonneland, Anne
    Lund, Eiliv
    Weiderpass, Elisabete
    Jenab, Mazda
    Fedirko, Veronika
    Offerhaus, G Johan A
    Riboli, Elio
    González, Carlos A
    Jakszyn, Paula
    Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2013In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 34, no 6, 1244-1250 p.Article in journal (Refereed)
    Abstract [en]

    Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

  • 6. Ahlberg, Alexander
    et al.
    Nikolaidis, Polymnia
    Engström, Therese
    Gunnarsson, Karin
    Johansson, Hemming
    Sharp, Lena
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Morbidity of supraomohyoidal and modified radical neck dissection combined with radiotherapy for head and neck cancer: a prospective longitudinal study2012In: Head and Neck, ISSN 1043-3074, E-ISSN 1097-0347, Vol. 34, no 1, 66-72 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of this study was to show the investigated impact of supraomohyoidal neck dissection and modified radical neck dissection, both combined with radiotherapy, on cervical range of motion (CROM), mouth opening, swallowing, lymphedema, and shoulder function.

    METHODS: One hundred eight patients who had neck dissections and 98 patients who had non-neck dissections were evaluated in a prospective, nonselective, longitudinal cohort study by a physiotherapist and a speech-language pathologist (SLP) before the start of radiotherapy and up to 12 months after treatment.

    RESULTS: The incidence of shoulder disability after neck dissection was 18%. Supraomohyoidal neck dissection had no significant effect on the evaluated parameters at any time point. Modified radical neck dissection significantly reduced CROM and mouth opening 2 months after treatment, but after 12 months only cervical rotation was still significantly reduced.

    CONCLUSION: In patients treated with external beam radiation (EBRT), modified radical neck dissection induced additional morbidity regarding CROM but not regarding mouth opening, swallowing, and lymphedema 1 year after treatment. Both modified radical neck dissection and supraomohyoidal neck dissection induced shoulder disability.

  • 7. Aleksandrova, Krasimira
    et al.
    Bamia, Christina
    Drogan, Dagmar
    Lagiou, Pagona
    Trichopoulou, Antonia
    Jenab, Mazda
    Fedirko, Veronika
    Romieu, Isabelle
    Bueno-de-Mesquita, H. Bas
    Pischon, Tobias
    Tsilidis, Kostas
    Overvad, Kim
    Tjønneland, Anne
    Bouton-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Kaaks, Rudolf
    Kuehn, Tilman
    Tsironis, Christos
    Papatesta, Eleni-Maria
    Saitakis, George
    Palli, Domenico
    Panico, Salvatore
    Grioni, Sara
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Weiderpass, Elisabete
    Lukic, Marko
    Braaten, Tonje
    Ramon Quiros, J.
    Lujan-Barroso, Leila
    Sanchez, Mara-Jose
    Chilarque, Maria-Dolores
    Ardanas, Eva
    Dorronsoro, Miren
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wallström, Peter
    Ohlsson, Bodil
    Bradbury, Kathryn E.
    Khaw, Kay-Tee
    Wareham, Nick
    Stepien, Magdalena
    Duarte-Salles, Talita
    Assi, Nada
    Murphy, Neil
    Gunter, Marc J.
    Riboli, Elio
    Boeing, Heiner
    Trichopoulos, Dimitrios
    The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition2015In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, no 6, 1498-1508 p.Article in journal (Refereed)
    Abstract [en]

    Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

  • 8. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Jenab, Mazda
    Bas Bueno-de-Mesquita, H
    Jansen, Eugene
    van Duijnhoven, Fränzel J B
    Fedirko, Veronika
    Rinaldi, Sabina
    Romieu, Isabelle
    Riboli, Elio
    Romaguera, Dora
    Overvad, Kim
    Ostergaard, Jane Nautrup
    Olsen, Anja
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Masala, Giovanna
    Agnoli, Claudia
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Trichopoulou, Antonia
    Naska, Androniki
    Bamia, Christina
    Peeters, Petra H
    Rodríguez, Laudina
    Buckland, Genevieve
    Sánchez, María-José
    Dorronsoro, Miren
    Huerta, Jose-María
    Barricarte, Aurelio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Allen, Naomi E
    Tsilidis, Konstantinos K
    Pischon, Tobias
    Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutrition study.2011In: Cancer prevention research (Philadelphia, Pa.), ISSN 1940-6215, Vol. 4, no 11, 1873-83 p.Article in journal (Refereed)
    Abstract [en]

    Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case-control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16-1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57-2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45-2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47-2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02-2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions. Cancer Prev Res; 4(11); 1873-83. ©2011 AACR.

  • 9. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Jenab, Mazda
    Bueno-de-Mesquita, H. Bas
    Jansen, Eugene
    van Duijnhoven, Franzel J. B.
    Rinaldi, Sabina
    Fedirko, Veronika
    Romieu, Isabelle
    Riboli, Elio
    Gunter, Marc J.
    Westphal, Sabine
    Overvad, Kim
    Tjonneland, Anne
    Halkjaer, Jytte
    Racine, Antoine
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Mattiello, Amalia
    Pala, Valeria
    Palli, Domenico
    Tumino, Rosario
    Vineis, Paolo
    Buckland, Genevieve
    Sanchez, Maria-Jose
    Amiano, Pilar
    Maria Huerta, Jose
    Barricarte, Aurelio
    Menendez, Virginia
    Peeters, Petra H.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Allen, Naomi E.
    Crowe, Francesca L.
    Khaw, Kay-Tee
    Wareham, Nickolas
    Pischon, Tobias
    Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into Cancer and nutrition cohort2012In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 72, no 20, 5328-5337 p.Article in journal (Refereed)
    Abstract [en]

    Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P-trend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P-trend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P-trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P-trend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328-37. (C) 2012 AACR.

  • 10. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Jenab, Mazda
    Bueno-de-Mesquita, H Bas
    Jansen, Eugene
    van Duijnhoven, Fränzel JB
    Fedirko, Veronika
    Rinaldi, Sabina
    Romieu, Isabelle
    Riboli, Elio
    Romaguera, Dora
    Westphal, Sabine
    Overvad, Kim
    Tjønneland, Anne
    Boutron-Ruault, Marie Christine
    Clavel-Chapelon, Françoise
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Agnoli, Claudia
    Mattiello, Amalia
    Saieva, Calogero
    Vineis, Paolo
    Tumino, Rosario
    Peeters, Petra H
    Argüelles, Marcial
    Bonet, Catalina
    Sánchez, María-José
    Dorronsoro, Miren
    Huerta, Jose-María
    Barricarte, Aurelio
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca L
    Pischon, Tobias
    Total and high-molecular-weight adiponectin and risk of colorectal cancer: the European prospective investigation into cancer and nutrition study2012In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 33, no 6, 1211-1218 p.Article in journal (Refereed)
    Abstract [en]

    Adiponectin - an adipose-tissue-derived protein may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular-weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite they were hypothesised to have differential biological activities, i.e. regulating insulin sensitivity (HMW-adiponectin) versus inflammatory response (non-HMW-adiponectin). In a prospective nested case-control study we investigated whether pre-diagnostic serum concentrations of total, HMW and non-HMW-adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon, 451 rectal) were matched to 1206 controls using incidence density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW-adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P (trend)=0.03 for total adiponectin and 0.45, 95%CI=0.34-0.61, P (trend)<0.0001 for non-HMW-adiponectin]. HMW-adiponectin concentrations were not associated with CRC risk (RR=0.91, 95%CI=0.68-1.22, P (trend)=0.55). Non-HMW-adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR=0.39, 95%CI=0.26-0.60, P (trend)<0.0001); whereas the association with total adiponectin was no longer significant (RR=0.81, 95%CI=0.60-1.09, P (trend)=0.23). When stratified by cancer site, non-HMW-adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW-adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.

  • 11. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Nöthlings, Ute
    Jenab, Mazda
    Fedirko, Veronika
    Kaaks, Rudolf
    Lukanova-McGregor, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Boffetta, Paolo
    Trepo, Elisabeth
    Westhpal, Sabine
    Duarte-Salles, Talita
    Stepien, Magdalena
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Lagiou, Pagona
    Bamia, Christina
    Benetou, Vassiliki
    Agnoli, Claudia
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, Bas
    Peeters, Petra H
    Gram, Inger Torhild
    Lund, Eiliv
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, María-José
    Gavrila, Diana
    Barricarte, Aurelio
    Dorronsoro, Miren
    Ohlsson, Bodil
    Lindkvist, Björn
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Riboli, Elio
    Pischon, Tobias
    Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 3, 858-871 p.Article in journal (Refereed)
    Abstract [en]

    Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

  • 12. Aleksandrova, Krasimira
    et al.
    Chuang, Shu-Chun
    Boeing, Heiner
    Zuo, Hui
    Tell, Grethe S
    Pischon, Tobias
    Jenab, Mazda
    Bueno-de-Mesquita, Bas
    Vollset, Stein Emil
    Midttun, Øivind
    Ueland, Per Magne
    Fedirko, Veronika
    Johansson, Mattias
    Weiderpass, Elisabete
    Severi, Gianluca
    Racine, Antoine
    Boutron-Ruault, Marie-Christine
    Kaaks, Rudolf
    Kühn, Tilman
    Tjønneland, Anne
    Overvad, Kim
    Quirós, J Ramón
    Jakszyn, Paula
    Sánchez, María-José
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Travis, Ruth C
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Panico, Salvatore
    May, Anne M
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kong, So Yeon J
    Freisling, Heinz
    Gunter, Marc J
    Lu, Yunxia
    Cross, Amanda J
    Riboli, Elio
    Vineis, Paolo
    A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk2015In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, no 4, djv010Article in journal (Refereed)
    Abstract [en]

    Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.

  • 13. Aleksandrova, Krasimira
    et al.
    Drogan, Dagmar
    Boeing, Heiner
    Jenab, Mazda
    Bas Bueno-de-Mesquita, H
    Jansen, Eugene
    van Duijnhoven, Fränzel J B
    Rinaldi, Sabina
    Fedirko, Veronika
    Romieu, Isabelle
    Kaaks, Rudolf
    Riboli, Elio
    Gunter, Marc J
    Romaguera, Dora
    Westhpal, Sabine
    Overvad, Kim
    Tjønneland, Anne
    Halkjaer, Jytte
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Lukanova, Annekatrin
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Vidalis, Pavlos
    Panico, Salvatore
    Agnoli, Claudia
    Palli, Domenico
    Tumino, Rosario
    Vineis, Paolo
    Buckland, Genevieve
    Sánchez-Cruz, José-Juan
    Dorronsoro, Miren
    Díaz, María José Tormo
    Barricarte, Aurelio
    Ramon Quiros, J
    Peeters, Petra H
    May, Anne M
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Crowe, Francesca L
    Khaw, Kay-Tee
    Wareham, Nickolas
    Pischon, Tobias
    Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 3, 612-621 p.Article in journal (Refereed)
    Abstract [en]

    Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend  = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend  = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.

  • 14. Aleksandrova, Krasimira
    et al.
    Jenab, Mazda
    Bueno-de-Mesquita, H. Bas
    Fedirko, Veronika
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    van Duijnhoven, Franzel J. B.
    Jansen, Eugene
    Rinaldi, Sabina
    Romieu, Isabelle
    Ferrari, Pietro
    Murphy, Neil
    Gunter, Marc J.
    Riboli, Elio
    Westhpal, Sabine
    Overvad, Kim
    Tjonneland, Anne
    Halkjaer, Jytte
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Trichopoulou, Antonia
    Bamia, Christina
    Orfanos, Philippos
    Agnoli, Claudia
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Duell, Eric J.
    Molina-Montes, Esther
    Ramon Quiros, J.
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Travis, Ruth C.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Pischon, Tobias
    Boeing, Heiner
    Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)2014In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 29, no 4, 261-275 p.Article in journal (Refereed)
    Abstract [en]

    A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.

  • 15. Aleksandrova, Krasimira
    et al.
    Pischon, Tobias
    Jenab, Mazda
    Bueno-de-Mesquita, H Bas
    Fedirko, Veronika
    Norat, Teresa
    Romaguera, Dora
    Knüppel, Sven
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Dartois, Laureen
    Kaaks, Rudolf
    Li, Kuanrong
    Tjønneland, Anne
    Overvad, Kim
    Quirós, José Ramón
    Buckland, Genevieve
    Sánchez, María José
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Bradbury, Kathryn E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Krogh, Vittorio
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Siersema, Peter D
    Peeters, Petra HM
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ericson, Ulrika
    Ohlsson, Bodil
    Weiderpass, Elisabete
    Skeie, Guri
    Borch, Kristin
    Rinaldi, Sabina
    Romieu, Isabelle
    Kong, Joyce
    Gunter, Marc J
    Ward, Heather A
    Riboli, Elio
    Boeing, Heiner
    Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study2014In: BMC Medicine, ISSN 1741-7015, Vol. 12, no 1, 168- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

  • 16.
    Alevronta, Eleftheria
    et al.
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden.
    Ahlberg, Alexander
    Department of Otolaryngology, Karolinska University Hospital, Stockholm, Sweden.
    Mavroidis, Panayiotis
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden.
    al-Abany, Massoud
    Department of Oncology-Pathology, Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Friesland, Signe
    Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
    Tilikidis, Aris
    Department of Medical Physics, Karolinska University Hospital, Stockholm, Sweden.
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Lind, Bengt K
    Department of Oncology-Pathology, Division of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Sweden.
    Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy2010In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 97, no 1, 54-59 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck.

    MATERIAL AND METHODS: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model.

    RESULTS: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D(50)=61.5 Gy (52.9-84.9 Gy), γ=1.4 (0.8-2.6) and s=0.1 (0.01-0.3).

    CONCLUSIONS: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.

  • 17. Alexandrie, A K
    et al.
    Warholm, M
    Carstensen, Ulrica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Axmon, A
    Hagmar, L
    Levin, Jan-Olof
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ostman, C
    Rannug, A
    CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure2000In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 21, no 4, 669-676 p.Article in journal (Refereed)
    Abstract [en]

    Certain human biotransformation enzymes have been implicated in the formation and scavenging of the ultimate reactive metabolites, the diolepoxides, from polycyclic aromatic hydrocarbons (PAHs). In the present study, performed on aluminum smelter workers, we have analyzed airborne PAH, the pyrene metabolite 1-hydroxypyrene (1-OHP) in urine, and genotypes for biotransformation enzymes involved in PAH metabolism. The aim was to evaluate the correlation between external exposure and biomarkers of exposure and to investigate to what extent genetic polymorphism in metabolic enzymes can explain interindividual variation in urinary 1-OHP levels. DNA was prepared from blood samples from 98 potroom workers and 55 controls and altogether eight polymorphisms in the CYP1A1, mEH, GSTM1, GSTP1 and GSTT1 genes were analyzed. The 1-OHP excretion was found to correlate significantly (P </= 0.005) to the exposure. The interindividual difference in excretion of 1-OHP was vast (>100-fold) and univariate and multivariate regression analyses were used to find the variables that could determine differences in excretion. The variation could, to some degree, be explained by differences in exposure to airborne particulate-associated PAHs, the use of personal respiratory protection devices, smoking habits and genetic polymorphisms in the cytochrome P450 1A1, GSTM1 and GSTT1 enzymes. The part of the variance that could be explained by differences in biotransformation genotypes seemed to be of the same order of magnitude as the variance explained by differences in exposure. In the control group as well as in the occupationally exposed group, the highest 1-OHP levels were observed in individuals carrying the CYP1A1 Ile/Val genotype who were also of the GSTM1 null genotype. The results show that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that it may also to some extent reflect the interindividual variation in susceptibility to PAHs.

  • 18.
    Alexeyev, Oleg
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Bergh, Johanna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Marklund, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wiklund, Fredrik
    Grönberg, Henrik
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden)2006In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 17, no 9, 1127-1133 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To study bacterial 16S RNA in archival prostate samples from 352 patients with benign prostate hyperplasia (BPH) and evaluate whether the presence of bacterial DNA was different in those who later developed prostate cancer (n = 171) and in the matched controls that did not progress to cancer (n = 181).

    Methods: 16S DNA PCR followed by cloning and sequencing the positive samples.

    Results: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected. Sequence analysis revealed Propionibacterium acnes as the predominant microorganism (23% of 16S RNA positive patients). The second most frequent isolate—Escherichia coli was found in 12 (12%) patients. The other isolates included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans (1), Corynebacterium sp. (2),Nocardioides sp. (1), Rhodococcus sp. (1) Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe histological inflammation versus 50% in the bacteria-negative group (p = 0.602). The presence of P. acnes in the prostate was associated with prostate cancer development (OR 2.17, 95% CI 0.77–6.95).

    Conclusions: This study has revealed P. acnes as the most common bacteria in the prostate in BPH. Further studies are needed to clarify its role in contributing to the development of prostatic inflammation and prostate cancer.

  • 19. Ali, Alaa M. G.
    et al.
    Schmidt, Marjanka K.
    Bolla, Manjeet K.
    Wang, Qin
    Gago-Dominguez, M.
    Esteban Castelao, J.
    Carracedo, Angel
    Munoz Garzon, Victor
    Bojesen, Stig E.
    Nordestgaard, Borge G.
    Flyger, Henrik
    Chang-Claude, Jenny
    Vrieling, Alina
    Rudolph, Anja
    Seibold, Petra
    Nevanlinna, Heli
    Muranen, Taru A.
    Aaltonen, Kirsimari
    Blomqvist, Carl
    Matsuo, Keitaro
    Ito, Hidemi
    Iwata, Hiroji
    Horio, Akiyo
    John, Esther M.
    Sherman, Mark
    Lissowska, Jolanta
    Figueroa, Jonine
    Garcia-Closas, Montserrat
    Anton-Culver, Hoda
    Shah, Mitul
    Hopper, John L.
    Trichopoulou, Antonia
    Bueno-de-Mesquita, Bas
    Krogh, Vittorio
    Weiderpass, Elisabete
    Andersson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Clavel-Chapelon, Francoise
    Dossus, Laure
    Fagherazzi, Guy
    Peeters, Petra H.
    Olsen, Anja
    Wishart, Gordon C.
    Easton, Douglas F.
    Borgquist, Signe
    Overvad, Kim
    Barricarte, Aurelio
    Gonzalez, Carlos A.
    Sanchez, Maria-Jose
    Amiano, Pilar
    Riboli, Elio
    Key, Tim
    Pharoah, Paul D.
    Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases2014In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 6, 934-945 p.Article in journal (Refereed)
    Abstract [en]

    Background: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre-or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer-specific mortality in ER-negative disease. Impact: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer.

  • 20. Allen, Naomi E
    et al.
    Appleby, Paul N
    Key, Timothy J
    Bueno-de-Mesquita, H B
    Ros, Martine M
    Kiemeney, Lambertus A L M
    Tjønneland, Anne
    Roswall, Nina
    Overvad, Kim
    Weikert, Steffen
    Boeing, Heiner
    Chang-Claude, Jenny
    Teucher, Birgit
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Palli, Domenico
    Sieri, Sabina
    Peeters, Petra
    Quirós, Jose Ramón
    Jakszyn, Paula
    Molina-Montes, Esther
    Chirlaque, María-Dolores
    Ardanaz, Eva
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Wareham, Nick
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ehrnström, Roy
    Ericson, Ulrika
    Gram, Inger Torhild
    Parr, Christine L
    Trichopoulou, Antonia
    Karapetyan, Tina
    Dilis, Vardis
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherrazzi, Guy
    Romieu, Isabelle
    Gunter, Marc J
    Riboli, Elio
    Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 3, 635-644 p.Article in journal (Refereed)
    Abstract [en]

    Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.

  • 21. Allen, Naomi E.
    et al.
    Travis, Ruth C.
    Appleby, Paul N.
    Albanes, Demetrius
    Barnett, Matt J.
    Black, Amanda
    Bueno-de-Mesquita, H. Bas
    Deschasaux, Melanie
    Galan, Pilar
    Goodman, Gary E.
    Goodman, Phyllis J.
    Gunter, Marc J.
    Heliovaara, Markku
    Helzlsouer, Kathy J.
    Henderson, Brian E.
    Hercberg, Serge
    Knekt, Paul
    Kolonel, Laurence N.
    Lasheras, Christina
    Linseisen, Jakob
    Metter, E. Jeffrey
    Neuhouser, Marian L.
    Olsen, Anja
    Pala, Valeria
    Platz, Elizabeth A.
    Rissanen, Harri
    Reid, Mary E.
    Schenk, Jeannette M.
    Stampfer, Meir J.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Tangen, Catherine M.
    Touvier, Mathilde
    Trichopoulou, Antonia
    van den Brandt, Piet A.
    Key, Timothy J.
    Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies2016In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, no 11, djw153Article in journal (Refereed)
    Abstract [en]

    Background: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. Methods: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. Results: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, P-heterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, P-trend <.001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, P-heterogeneity =.08). Conclusions: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

  • 22. Amirian, E. Susan
    et al.
    Armstrong, Georgina N.
    Zhou, Renke
    Lau, Ching C.
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill S.
    Il'yasova, Dora
    Schildkraut, Joellen
    Ali-Osman, Francis
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard S.
    Jenkins, Robert B.
    Lachance, Daniel
    Olson, Sara H.
    Bernstein, Jonine L.
    Merrell, Ryan T.
    Wrensch, Margaret R.
    Davis, Faith G.
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher I.
    Scheurer, Michael E.
    Aldape, Kenneth
    Alafuzoff, Irina
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Broholm, Helle
    Collins, Peter
    Giannini, Caterina
    Rosenblum, Marc
    Tihan, Tarik
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bondy, Melissa L.
    The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium2016In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 183, no 2, 85-91 p.Article in journal (Refereed)
    Abstract [en]

    Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.

  • 23. Amirian, E. Susan
    et al.
    Armstrong, Georgina
    Zhou, Renke
    Wrensch, Margaret
    Olson, Sara
    Scheurer, Michael
    Il'yasova, Dora
    Lachance, Daniel
    Lau, Ching
    Claus, Elizabeth
    Barnholtz-Sloan, Jill
    Schildkraut, Joellen
    Ali-Osman, Francis
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard
    Jenkins, Robert
    Bernstein, Jonine
    Merrell, Ryan
    Davis, Faith
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    DEMOGRAPHICS AND LIFESTYLE FACTORS IN GLIOMA RISK: A REPORT FROM THE GLIOMA INTERNATIONAL CASE-CONTROL STUDY2016In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 18, 57-58 p.Article in journal (Refereed)
  • 24. Amirian, E. Susan
    et al.
    Scheurer, Michael E.
    Wrensch, Margaret
    Olson, Sara H.
    Lai, Rose
    Lachance, Daniel
    Armstrong, Georgina
    Zhou, Renke
    Wiemels, Joseph
    Lau, Ching
    Claus, Elizabeth
    Barnholtz-Sloan, Jill
    Il'yasova, Dora
    Schildkraut, Joellen
    Houlston, Richard
    Shete, Sanjay
    Bernstein, Jonine
    Jenkins, Robert
    Davis, Faith
    Merrell, Ryan
    Johansen, Christoffer
    Sadetzki, Siegal
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    ATOPIC CONDITIONS, ANTIHISTAMINE USE, AND GLIOMA RISK: PRELIMINARY RESULTS FROM THE GLIOMA INTERNATIONAL CASE-CONTROL STUDY2013In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 15, no Supplement: 3, 32-32 p.Article in journal (Other academic)
  • 25. Amirian, E. Susan
    et al.
    Scheurer, Michael E.
    Zhou, Renke
    Wrensch, Margaret R.
    Armstrong, Georgina N.
    Lachance, Daniel
    Olson, Sara H.
    Lau, Ching C.
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill S.
    Il'yasova, Dora
    Schildkraut, Joellen
    Ali-Osman, Francis
    Sadetzki, Siegal
    Jenkins, Robert B.
    Bernstein, Jonine L.
    Merrell, Ryan T.
    Davis, Faith G.
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher I.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa L.
    History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC)2016In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 5, no 6, 1352-1358 p.Article in journal (Refereed)
    Abstract [en]

    Varicella zoster virus (VZV) is a neurotropic alpha-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted.

  • 26. Amirian, E. Susan
    et al.
    Zhou, Renke
    Wrensch, Margaret R.
    Olson, Sara H.
    Scheurer, Michael E.
    Il'yasova, Dora
    Lachance, Daniel
    Armstrong, Georgina N.
    McCoy, Lucie S.
    Lau, Ching C.
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill S.
    Schildkraut, Joellen
    Ali-Osman, Francis
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard S.
    Jenkins, Robert B.
    Bernstein, Jonine L.
    Merrell, Ryan T.
    Davis, Faith G.
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher I.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa L.
    Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: a report from the Glioma International Case-Control Study2016In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 25, no 2, 282-290 p.Article in journal (Refereed)
    Abstract [en]

    Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusion: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. (C) 2016 AACR.

  • 27. Anantharaman, Devasena
    et al.
    Gheit, Tarik
    Waterboer, Tim
    Halec, Gordana
    Carreira, Christine
    Abedi-Ardekani, Behnoush
    McKay-Chopin, Sandrine
    Zaridze, David
    Mukeria, Anush
    Szeszenia-Dabrowska, Neonila
    Lissowska, Jolanta
    Mates, Dana
    Janout, Vladimir
    Foretova, Lenka
    Bencko, Vladimir
    Rudnai, Peter
    Fabianova, Eleonora
    Tjonneland, Anne
    Travis, Ruth C
    Boeing, Heiner
    Quiros, J Ramon
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Krogh, Vittorio
    Bueno-de-Mesquita, H Bas
    Kotanidou, Anastasia
    Clavel-Chapelon, Francoise
    Weiderpass, Elisabete
    Johansson, Mattias
    Pawlita, Michael
    Scelo, Ghislaine
    Tommasino, Massimo
    Brennan, Paul
    No causal association identified for human papillomavirus infections in lung cancer2014In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 13, 3525-3534 p.Article in journal (Refereed)
    Abstract [en]

    Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case-control studies (retrospective) and one nested case-control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer. (C) 2014 AACR.

  • 28. Anantharaman, Devasena
    et al.
    Muller, David C
    Lagiou, Pagona
    Ahrens, Wolfgang
    Holcátová, Ivana
    Merletti, Franco
    Kjærheim, Kristina
    Polesel, Jerry
    Simonato, Lorenzo
    Canova, Cristina
    Castellsague, Xavier
    Macfarlane, Tatiana V
    Znaor, Ariana
    Thomson, Peter
    Robinson, Max
    Conway, David I
    Healy, Claire M
    Tjønneland, Anne
    Westin, Ulla
    Ekström, Johanna
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Overvad, Kim
    Drogan, Dagmar
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Laurell, Göran
    Bueno-de-Mesquita, H B
    Peeters, Petra H
    Agudo, Antonio
    Larrañaga, Nerea
    Travis, Ruth C
    Palli, Domenico
    Barricarte, Aurelio
    Trichopoulou, Antonia
    George, Saitakis
    Trichopoulos, Dimitrios
    Quirós, J Ramón
    Grioni, Sara
    Sacerdote, Carlotta
    Navarro, Carmen
    Sánchez, María-José
    Tumino, Rosario
    Severi, Gianluca
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Panico, Salvatore
    Weiderpass, Elisabete
    Lund, Eiliv
    Gram, Inger T
    Riboli, Elio
    Pawlita, Michael
    Waterboer, Tim
    Kreimer, Aimée R
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Brennan, Paul
    Combined effects of smoking and HPV16 in oropharyngeal cancer2016In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 45, no 3, 752-761 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.

    METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.

    RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.

    CONCLUSIONS: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

  • 29.
    Andersson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Long-term side effects after treatment of Hodgkin's lymphoma2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Long-term side effects associated with the treatment of Hodgkin’s lymphoma (HL) have frequently been reported during the last decades. Studies have shown increased mortality in HL survivors. Following Hodgkin’s lymphoma, second malignancies (SM) and cardiovascular disease (CVD) are the most common causes of death in individuals treated for HL. This study investigates the incidence of side effects such as SM, CVD and infections in a cohort diagnosed with HL in Sweden between 1965 and 1995. In addition, this study identifies covariate risk factors for late side effects in order to develop strategies that prevent morbidity and mortality in HL survivors.

    Methods Using the Swedish Cancer Registry (SCR) at the National Board of Health and Welfare and the Multi-Generation Registry at Statistics (MGR) Sweden, we identified 6946 individuals diagnosed with HL between the years 1965 and 1995, and their first degree relatives (FDR) (n=17 858). In addition we identified the malignancies and inpatient care for CVD and infections for the HL cohort and their FDR. The standard incidence ratio (SIR) was calculated for the risk of SM, CVD and infections. For SM and CVD the risk also was stratified and calculated for family history of disease. The Swedish Hodgkin Intervention and Prevention study (SHIP), a prospective study, invited 702 individuals treated for HL at the age of 45 years or younger and who were treated in the region of Skåne, Uppsala or Umeå. The participants completed a questionnaire and were invited to an out-patient visit to an oncologist with clinical examination and blood tests. Any pathological findings were referred for further investigation.

    Results An increased risk for SM in HL long-term survivors was observed and seems to increase with the number of FDRs with cancer. There was also an increased risk for inpatient care due to congestive heart failure (CHF) and coronary artery disease (CAD). A family history of CHF and CAD further increased the risk for these diseases. The risk for inpatient care due to infections was increased and remained increased after 20 years or longer. The risk for infections was associated with splenectomy and hypothyroidism. Radiotherapy was an independent risk factor for cardiovascular disease in the cohort of the prospective study.

    ConclusionLong-term survivors from HL have an increased risk for developing late side effects such as SM, CVD and infections. Since many HL patients are young and the cure rate from the disease is high, it is of great importance to offer focused surveillance programs to selected individuals who are at high risk, e.g. individuals who received radiotherapy as part of their treatment and who have other known risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, family history and smoking.

  • 30.
    Andersson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enblad, Gunilla
    Department of Oncology, Radiology and Clinical immunology, Section of Oncology, Uppsala University, Uppsala.
    Gustavsson, Anita
    Department of Oncology, Skåne University Hospital, Lund University, Lund .
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hagberg, Hans
    Department of Oncology, Radiology and Clinical immunology, Section of Oncology, Uppsala University, Uppsala .
    Molin, Daniel
    Department of Oncology, Radiology and Clinical immunology, Section of Oncology, Uppsala University, Uppsala .
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Long term risk of infections in Hodgkin lymphoma long-term survivors2011In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 154, no 5, 661-663 p.Article in journal (Refereed)
  • 31.
    Andersson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enblad, Gunilla
    Uppsala universitet.
    Gustavsson, Anita
    Lunds universitet.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hagberg, Hans
    Uppsala universitet.
    Molin, Daniel
    Uppsala universitet.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cardiovascular side effects following treatment of Hodgkin’s lymphoma: comorbidity factors and a strategy for interventionManuscript (preprint) (Other academic)
  • 32.
    Andersson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enblad, Gunilla
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björkholm, Magnus
    Linderoth, Johan
    Lagerlöf, I
    Merup, Mats
    Sender, Mark
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma2008In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 98, no 5, 1001-1005 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 33.
    Andersson, Anne
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Tavelin, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Enblad, Gunilla
    Gustavsson, Anita
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors: retrospective cohort analyses and a concept for prospective intervention2009In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, no 8, 1914-1917 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 34. Andersson, Carola
    et al.
    Österlundh, Gustaf
    Enlund, Fredrik
    Kindblom, Lars-Gunnar
    Hansson, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: a paediatric case report and review of the literature2014In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 4, 1608-1612 p.Article, review/survey (Refereed)
    Abstract [en]

    Mesenchymal chondrosarcoma is an extremely rare malignant tumour that most commonly originates in the bone, but is also present in extraskeletal sites. The tumour is morphologically characterized by a biphasic pattern of small round cells and islands of cartilage. Spinal mesenchymal chondrosarcomas are even rarer and, therefore, few investigations exist regarding the biological behaviour of the tumours. In the present study, we report a case of a 10-year-old female presenting with 9 months of back pain and radiographic findings of an intradural lesion measuring 1.5 cm at the level of Th4. The tumour was completely excised and subjected to pathological analyses. Following detection of the HEY1-NCOA2 fusion gene, the tumour was morphologically and immunohistochemically defined as an intradural mesenchymal chondrosarcoma attached to the dura mater. In this study, we validate the recent identification of the fusion gene HEY1-NCOA2 in paediatric extraskeletal mesenchymal chondrosarcomas: The relevant literature is reviewed and further discussed in relation to our findings.

  • 35.
    Andersson, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Oji, Yusuke
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wang, Sihan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Li, Xingru
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Ottander, Ulrika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sugiyama, Haruo
    Li, Aihong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Prognostic significance of specific anti-WT1 IgG antibody level in plasma in patients with ovarian carcinoma2014In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 3, no 4, 909-918 p.Article in journal (Refereed)
    Abstract [en]

    Ovarian carcinoma (OC) has a poor prognosis and lack early effective screening markers. Wilm's tumor gene 1 (WT1) is overexpressed in OCs. Therefore, it is of great interest to investigate whether WT1-specific antibody (Ab) measurements in plasma can serve as a biomarker of anti-OC response, and is of importance in relation to patient prognosis. Peripheral blood samples were obtained from a total of 103 women with ovarian tumors with median being 1 day (range 0-48 days) before operation. WT1 IgG Ab levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis of WT1 protein expression was performed on OC tissue samples. We found that low-WT1 Ab level in plasma was related to improved survival in patients diagnosed at stages III-IV and grade 3 carcinomas. Positive WT1 protein staining on OC tissue samples had a negative impact on survival in the entire cohort, both overall survival (OS) (P = 0.046) and progression-free survival (PFS) (P = 0.006), but not in the serous OC subtype. Combining WT1 IgG Ab levels and WT1 staining, patients with high-WT1 IgG Ab levels in plasma and positive WT1 protein staining in cancer tissues had shorter survival, with a significant association in PFS (P = 0.016). These results indicated that WT1 Ab measurements in plasma and WT1 staining in tissue specimens could be useful as biomarkers for patient outcome in the high-risk subtypes of OCs for postoperative individualized therapy.

  • 36.
    Andersson, Jesper
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Low frequency of sequence variants in EEF1A1 in clear cell Renal Cell Carcinoma2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 37.
    Andersson, Kristin
    et al.
    Laboratory Medicine, Lund University, Malm ö , Sweden.
    Bray, Freddie
    Cancer Registry of Norway, Oslo, Norway.
    Arbyn, Marc
    Unit of Cancer Epidemiology, Scientifi c Institute of Public Health, Brussels, Belgium.
    Storm, Hans
    Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen, Denmark.
    Zanetti, Roberto
    Piedmont Cancer Registry – CPO, Torino, Italy.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Coebergh, Jan W
    Comprehensive Cancer Centre South, Eindhoven, Netherlands.
    Dillner, Joakim
    Laboratory Medicine, Lund University, Malmö, Sweden.
    The interface of population-based cancer registries and biobanks in etiological and clinical research: current and future perspectives2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 8, 1227-1234 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The availability of quality assured, population-based cancer registries and biobanks with high quality samples makes it possible to conduct research on large samples sets with long follow-up within a reasonable time frame. Defined quality for both cancer registries and biobanks is essential for enabling high quality biobank-based research. Recent networking projects have brought these infrastructures together to promote the combined use of cancer registries and biobanks in cancer research.

    MATERIALS AND METHODS: In this report we review the current status and future perspectives of cancer registries and biobanks and how the interface between them should be developed to optimally further cancer research.

    RESULTS AND DISCUSSION: Major conclusions for future improvements are that the research exploiting cancer registries and biobanks, and the research that is building and optimising the infrastructure, should evolve together for maximally relevant progress. Population-based and sustainable biobanks that continuously and consecutively store all samples ("Biological registries") under strict quality control are needed. There is also a need for increased education, information and visibility of the interdisciplinary sciences required for optimal exploitation of these resources.

  • 38.
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Experimental studies in brain tumours: with special regard to multidrug resistance and the ErbB-family2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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.

  • 39.
    Andersson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Degerman, Sofie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahlin, Anna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brannstrom, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Melin, B. S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    TELOMERE LENGTH, ALLERGIES AND RISK OF GLIOMA2017In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 19, no Supplement: 3, 23-23 p., Meeting Abstract: P01.03Article in journal (Refereed)
  • 40.
    Andersson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schwartzbaum, Judith
    Wiklund, Fredrik
    Sjöström, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Liu, Yanhong
    Tsavachidis, Spyros
    Ahlbom, Anders
    Auvinen, Anssi
    Collatz-Laier, Helle
    Feychting, Maria
    Johansen, Christoffer
    Kiuru, Anne
    Lönn, Stefan
    Schoemaker, Minouk J
    Swerdlow, Anthony J
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 6, 767-775 p.Article in journal (Refereed)
    Abstract [en]

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

  • 41.
    Andersson, Ulrika
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cederquist, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Aradottir, Steina
    Borg, Åke
    Armstrong, Georgina N.
    Shete, Sanjay
    Lau, Ching C.
    Bainbridge, Matthew N.
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill
    Lai, Rose
    Il'yasova, Dora
    Houlston, Richard S.
    Schildkraut, Joellen
    Bernstein, Jonine L.
    Olson, Sara H.
    Jenkins, Robert B.
    Lachance, Daniel H.
    Wrensch, Margaret
    Davis, Faith G.
    Merrell, Ryan
    Johansen, Christoffer
    Sadetzki, Siegal
    Bondy, Melissa L.
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer2014In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 16, no 10, 1333-1340 p.Article in journal (Refereed)
    Abstract [en]

    Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.

  • 42. Andren, O.
    et al.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Falt, A.
    Ulvskog, E.
    Davidsson, S.
    Thellenberg Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hjalm-Eriksson, M.
    Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A randomized, open label, phase III, multicenter trial2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28Article in journal (Other academic)
  • 43.
    Andræ, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Education, Uppsala University, Uppsala, Sweden.
    Facing death: physicians' difficulties and coping strategies in cancer care1994Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Even if the treatment of cancer has developed over the last decades 50% of the patients still die of their cancer. The doctor's way of dealing with his and his patient's anxiety must surely be of significance for the treatment the patient receives.

    In the first part of the thesis earlier studies of physicians' stress and ways of coping are reported. There is a lack of systematic studies which show how doctors working with cancer patients adjust to this work. The aim of this investigation is to study cancer doctors' difficulties and coping strategies. The theoretical frame of the study embraces parts of psychoanalytical theory and coping models, emphasizing that both unconscious and conscious psychological processes play their part in the coping process.

    The second, empirical part of the study includes 23 physicians strategically selected out of a population of physicians who work with institutional care and who have daily contact with adult cancer patients. The main method of data collection has been a series of recorded interviews. The focus of the interview was the physician's perception of how he reacts, thinks, talks and acts in different phases of the cancer disease. To illustrate the defence strategies of the interviewers, the projective percept-genetic test, the "Defence Mechanism Test" (DMT) is used. The "Structural Analysis of Social Behaviour" (SASB) has been used to study the doctors' self image.

    The results indicate that the stated difficulties deeply affect the doctor as a human being. The statements reflect conflicting feelings and wishes in relation to authority, conflicting feelings and wishes in relation to frightening and injuring, conflicting feelings and wishes in relation to intimacy/distance. Thirty themes of coping strategies frequently recur and they have been grouped into seven categories. Most of the doctors "seek knowledge" and support from scientific literature. The majority of them state that attempting to "solve a problem" is their main strategy. Most of the doctors "seek support " as a part of their coping strategy. An interesting observation is that the doctors to a higher extent "seek a relation" to their patients rather than to their colleagues. Almost one third use "denial of the severity of a situation" as their main strategy. All the doctors consciously or unconsciously use "diverting strategies", i.e. undertake tasks which are devoid of contact with patients, such as research and administration or other activities which allow them to avoid the patient. One third use "projective manoeuvres" but this is never a main strategy.

    In the third part of the study the credibility of the results and their pedagogical and practical implications are discussed.

  • 44. Antoniou, Antonis C
    et al.
    Beesley, Jonathan
    McGuffog, Lesley
    Sinilnikova, Olga M
    Healey, Sue
    Neuhausen, Susan L
    Ding, Yuan Chun
    Rebbeck, Timothy R
    Weitzel, Jeffrey N
    Lynch, Henry T
    Isaacs, Claudine
    Ganz, Patricia A
    Tomlinson, Gail
    Olopade, Olufunmilayo I
    Couch, Fergus J
    Wang, Xianshu
    Lindor, Noralane M
    Pankratz, Vernon S
    Radice, Paolo
    Manoukian, Siranoush
    Peissel, Bernard
    Zaffaroni, Daniela
    Barile, Monica
    Viel, Alessandra
    Allavena, Anna
    Dall'Olio, Valentina
    Peterlongo, Paolo
    Szabo, Csilla I
    Zikan, Michal
    Claes, Kathleen
    Poppe, Bruce
    Foretova, Lenka
    Mai, Phuong L
    Greene, Mark H
    Rennert, Gad
    Lejbkowicz, Flavio
    Glendon, Gord
    Ozcelik, Hilmi
    Andrulis, Irene L
    Thomassen, Mads
    Gerdes, Anne-Marie
    Sunde, Lone
    Cruger, Dorthe
    Birk Jensen, Uffe
    Caligo, Maria
    Friedman, Eitan
    Kaufman, Bella
    Laitman, Yael
    Milgrom, Roni
    Dubrovsky, Maya
    Cohen, Shimrit
    Borg, Åke
    Jernström, Helena
    Lindblom, Annika
    Rantala, Johanna
    Stenmark-Askmalm, Marie
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nathanson, Kate
    Domchek, Susan
    Jakubowska, Ania
    Lubinski, Jan
    Huzarski, Tomasz
    Osorio, Ana
    Lasa, Adriana
    Durán, Mercedes
    Tejada, Maria-Isabel
    Godino, Javier
    Benitez, Javier
    Hamann, Ute
    Kriege, Mieke
    Hoogerbrugge, Nicoline
    van der Luijt, Rob B
    van Asperen, Christi J
    Devilee, Peter
    Meijers-Heijboer, EJ
    Blok, Marinus J
    Aalfs, Cora M
    Hogervorst, Frans
    Rookus, Matti
    Cook, Margaret
    Oliver, Clare
    Frost, Debra
    Conroy, Don
    Evans, D Gareth
    Lalloo, Fiona
    Pichert, Gabriella
    Davidson, Rosemarie
    Cole, Trevor
    Cook, Jackie
    Paterson, Joan
    Hodgson, Shirley
    Morrison, Patrick J
    Porteous, Mary E
    Walker, Lisa
    Kennedy, M John
    Dorkins, Huw
    Peock, Susan
    Godwin, Andrew K
    Stoppa-Lyonnet, Dominique
    de Pauw, Antoine
    Mazoyer, Sylvie
    Bonadona, Valérie
    Lasset, Christine
    Dreyfus, Hélène
    Leroux, Dominique
    Hardouin, Agnès
    Berthet, Pascaline
    Faivre, Laurence
    Loustalot, Catherine
    Noguchi, Tetsuro
    Sobol, Hagay
    Rouleau, Etienne
    Nogues, Catherine
    Frénay, Marc
    Vénat-Bouvet, Laurence
    Hopper, John L
    Daly, Mary B
    Terry, Mary B
    John, Esther M
    Buys, Saundra S
    Yassin, Yosuf
    Miron, Alexander
    Goldgar, David
    Singer, Christian F
    Dressler, Anne Catharina
    Gschwantler-Kaulich, Daphne
    Pfeiler, Georg
    Hansen, Thomas VO
    Jønson, Lars
    Agnarsson, Bjarni A
    Kirchhoff, Tomas
    Offit, Kenneth
    Devlin, Vincent
    Dutra-Clarke, Ana
    Piedmonte, Marion
    Rodriguez, Gustavo C
    Wakeley, Katie
    Boggess, John F
    Basil, Jack
    Schwartz, Peter E
    Blank, Stephanie V
    Toland, Amanda Ewart
    Montagna, Marco
    Casella, Cinzia
    Imyanitov, Evgeny
    Tihomirova, Laima
    Blanco, Ignacio
    Lazaro, Conxi
    Ramus, Susan J
    Sucheston, Lara
    Karlan, Beth Y
    Gross, Jenny
    Schmutzler, Rita
    Wappenschmidt, Barbara
    Engel, Christoph
    Meindl, Alfons
    Lochmann, Magdalena
    Arnold, Norbert
    Heidemann, Simone
    Varon-Mateeva, Raymonda
    Niederacher, Dieter
    Sutter, Christian
    Deissler, Helmut
    Gadzicki, Dorothea
    Preisler-Adams, Sabine
    Kast, Karin
    Schönbuchner, Ines
    Caldes, Trinidad
    de la Hoya, Miguel
    Aittomäki, Kristiina
    Nevanlinna, Heli
    Simard, Jacques
    Spurdle, Amanda B
    Holland, Helene
    Chen, Xiaoqing
    Platte, Radka
    Chenevix-Trench, Georgia
    Easton, Douglas F
    Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction2010In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 70, no 23, 9742-9754 p.Article in journal (Refereed)
    Abstract [en]

    The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.

  • 45. Araghi, Marzieh
    et al.
    Galanti, Maria Rosaria
    Lundberg, Michael
    Lager, Anton
    Engström, Gunnar
    Alfredsson, Lars
    Knutsson, Anders
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Trolle Lagerros, Ylva
    Bellocco, Rino
    Pedersen, Nancy L.
    Östergren, Per-Olof
    Magnusson, Cecilia
    Use of moist oral snuff (snus) and pancreatic cancer: pooled analysis of nine prospective observational studies2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 4, 687-693 p.Article in journal (Refereed)
    Abstract [en]

    While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83–1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.

  • 46. Arason, Adalgeir
    et al.
    Gunnarsson, Haukur
    Johannesdottir, Gudrun
    Jonasson, Kristjan
    Bendahl, Pär-Ola
    Gillanders, Elizabeth M
    Agnarsson, Bjarni A
    Jönsson, Göran
    Pylkäs, Katri
    Mustonen, Aki
    Heikkinen, Tuomas
    Aittomäki, Kristiina
    Blomqvist, Carl
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johannsson, Oskar TH
    Møller, Pål
    Winqvist, Robert
    Nevanlinna, Heli
    Borg, Åke
    Barkardottir, Rosa B
    Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families2010In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 12, no 4, R50- p.Article in journal (Refereed)
    Abstract [en]

    Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.

  • 47.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Prediction of prognosis in human breast cancer: a study on clinicopathologic and cytometric prognostic factors1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This study was undertaken to evaluate some important prognostic factors in human breast cancer. The prognostic value of accepted clinicopathological factors such as the presence of axillary lymph node métastasés, histologic grade, clinical and pathological stage was confirmed.

    In a cohort of stage T3,T4,M0 breast cancer with 91 patients (paper I) DNA ploidy by static cytometry (SCM) turned out to be the most important prognostic factor. In a cohort of stage T2,M0 breast cancer with 99 patients (paper III) the presence of involved axillary nodes and low histologic grade were independent prognostic factors. According to life-table analyses DNA ploidy by flow cytometty (FCM) and SCM were significant prognostic predictors for survival but S-phase fraction (SPF) was not. The significant discrimination between euploid and aneuploid tumours was seen also among the node-negative patients. In a patient material with 158 tumours of predominantly low stages (73% T0,T1, papers IV and V) and calculated mammographie tumour volume doubling time (DT) DNA ploidy by FCM gave no significant prognostic information. A computer program was used to calculate SPF from the histograms obtained by FCM. SPF with a cut-off value of 7.5% between tumours with high and low proliferation rate was a highly significant and independent prognostic factor for survival. The other independent prognostic predictors were low histologic grade, the presence of involved axillary nodes and stage II and III (versus stage I).

    DT values for 158 patients (papers IV and V) varied between 0.6 and 65.8 months (mean 10.9 months) and 11 tumours showed no growth at all between mammographies. The median value of 9.0 months was chosen as cut-off point between slow and fast growing tumours. The prognostic power of DT was however low, and the difference between slow and fast growing tumours was significant only for distant disease-free survival. Seventy-one of the 158 tumours were detected by mammographie screening. The screening detected carcinomas with predominantly long DT:s were discovered at an early stage and showed favourable characteristics concerning DNA ploidy and SPF.

    FCM was a rapid and reliable method for DNA analysis with a better prognostic discrimination between euploid and aneuploid groups than SCM (papers II and III).

    SPF, DNA ploidy and histologic grade are significantly correlated to one another but show no strong correlation to the presence of axillary lymph node métastasés. There is also a significant correlation between DT on one hand and DNA ploidy and SPF on the other hand.

    In conclusion the classic prognostic factors are still valuable. DNA ploidy as a single prognostic factor seems to have a relatively low prognostic power and seems to be of limited clinical value. SPF is a highly significant prognostic predictor for breast cancer of low stage, but the clinical value is not defined.

  • 48. Arnold, Melina
    et al.
    Freisling, Heinz
    Stolzenberg-Solomon, Rachael
    Kee, Frank
    O'Doherty, Mark George
    Ordóñez-Mena, José Manuel
    Wilsgaard, Tom
    May, Anne Maria
    Bueno-de-Mesquita, Hendrik Bas
    Tjønneland, Anne
    Orfanos, Philippos
    Trichopoulou, Antonia
    Boffetta, Paolo
    Bray, Freddie
    Jenab, Mazda
    Soerjomataram, Isabelle
    Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States2016In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 31, no 9, 893-904 p.Article in journal (Refereed)
    Abstract [en]

    Recent studies have shown that cancer risk related to overweight and obesity is mediated by time and might be better approximated by using life years lived with excess weight. In this study we aimed to assess the impact of overweight duration and intensity in older adults on the risk of developing different forms of cancer. Study participants from seven European and one US cohort study with two or more weight assessments during follow-up were included (n = 329,576). Trajectories of body mass index (BMI) across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25) and cumulative weighted overweight years were calculated. In multivariate Cox models and random effects analyses, a longer duration of overweight was significantly associated with the incidence of obesity-related cancer [overall hazard ratio (HR) per 10-year increment: 1.36; 95 % CI 1.12-1.60], but also increased the risk of postmenopausal breast and colorectal cancer. Additionally accounting for the degree of overweight further increased the risk of obesity-related cancer. Risks associated with a longer overweight duration were higher in men than in women and were attenuated by smoking. For postmenopausal breast cancer, increased risks were confined to women who never used hormone therapy. Overall, 8.4 % of all obesity-related cancers could be attributed to overweight at any age. These findings provide further insights into the role of overweight duration in the etiology of cancer and indicate that weight control is relevant at all ages. This knowledge is vital for the development of effective and targeted cancer prevention strategies.

  • 49.
    Arslan, Alan A
    et al.
    Department of Environmental Medicine, New York University School of Medicine.
    Clendenen, Tess V
    Department of Environmental Medicine, New York University School of Medicine.
    Koenig, Karen L
    Department of Environmental Medicine, New York University School of Medicine.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Enquist, Kerstin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ågren, Åsa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lukanova, Annekatrin
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    Sjodin, Hubert
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Zeleniuch-Jacquotte, Anne
    Department of Environmental Medicine, New York University School of Medicine.
    Shore, Roy E
    Radiation Effects Research Foundation, Hiroshima, Japan.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Department of Environmental Medicine, New York University School of Medicine.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Circulating vitamin d and risk of epithelial ovarian cancer2009In: Journal of oncology, ISSN 1687-8450, Vol. 2009, 672492-672500 p.Article in journal (Refereed)
    Abstract [en]

    We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59-2.01). In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.

  • 50. Arslan, Alan A.
    et al.
    Koenig, Karen L.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Afanasyeva, Yelena
    Shore, Roy E.
    Chen, Yu
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Toniolo, Paolo
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Zeleniuch-Jacquotte, Anne
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Circulating Estrogen Metabolites and Risk of Breast Cancer in Postmenopausal Women2014In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 7, 1290-1297 p.Article in journal (Refereed)
    Abstract [en]

    Background: It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16 alpha-hydroxylation pathway may be inversely associated with breast cancer risk. Methods: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and the 2-OHE1: 16 alpha-OHE1 ratio in a case-control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16 alpha-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation. Results: Overall, no significant associations were observed between breast cancer risk and circulating levels of 2-OHE1, 16 alpha-OHE1, or their ratio in either cohort and in combined analyses. For 2-OHE1, there was evidence of heterogeneity by ER status in models adjusting for estrone (P <= 0.03). We observed a protective association of 2-OHE1 with ER + breast cancer [multivariate-adjusted OR for a doubling of 2-OHE1, 0.67 (95% confidence interval [CI], 0.48-0.94; P = 0.02)]. Conclusions: In this study, higher levels of 2-OHE1 were associated with reduced risk of ER + breast cancer in postmenopausal women after adjustment for circulating estrone. Impact: These results suggest that taking into account the levels of parent estrogens and ER status is important in studies of estrogen metabolites and breast cancer.

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