77 results on '"Ljuslinder I"'
Search Results
2. 570P Subclasses of microsatellite-instability colorectal cancer with unique molecular features and immune cell infiltration patterns
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Wu, K., Wu, M., Luo, T., Li, F., Nunes, L., Hammarström, K., Lundin, E., Ljuslinder, I., Mezheyeuski, A., Edqvist, P-H., Löfgren-Burström, A., Zingmark, C., Edin, S., Ponten, F., Palmqvist, R., Lin, C., Glimelius, B., and Sjöblom, T.
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- 2023
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3. 572P Neoantigen heterogeneity among subtypes in colorectal cancer
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Li, F., Luo, T., Nunes, L., Wu, M., Hammarström, K., Lundin, E., Ljuslinder, I., Mezheyeuski, A., Edqvist, P-H., Löfgren-Burström, A., Zingmark, C., Edin, S., Ponten, F., Palmqvist, R., Wu, K., Glimelius, B., Sjöblom, T., and Lin, C.
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- 2023
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4. Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition
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Cervenka, I. Al Rahmoun, M. Mahamat-Saleh, Y. Fournier, A. Boutron-Ruault, M.-C. Severi, G. Caini, S. Palli, D. Ghiasvand, R. Veierod, M.B. Botteri, E. Tjønneland, A. Olsen, A. Fortner, R.T. Kaaks, R. Schulze, M.B. Panico, S. Trichopoulou, A. Dessinioti, C. Niforou, K. Sieri, S. Tumino, R. Sacerdote, C. Bueno-de-Mesquita, B. Sandanger, T.M. Colorado-Yohar, S. Sánchez, M.J. Gil Majuelo, L. Lujan-Barroso, L. Ardanaz, E. Merino, S. Isaksson, K. Butt, S. Ljuslinder, I. Jansson, M. Travis, R.C. Khaw, K.-T. Weiderpass, E. Dossus, L. Rinaldi, S. Kvaskoff, M.
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Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations. © 2019 UICC
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- 2020
5. Phase II multicenter open label study of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study)
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Jespersen, H., primary, Olofsson Bagge, R., additional, Ullenhag, G., additional, Carneiro, A., additional, Helgadottir, H., additional, Ljuslinder, I., additional, Levin, M., additional, All-Eriksson, C., additional, Andersson, B., additional, Stierner, U., additional, Nilsson, L.M., additional, Nilsson, J.A., additional, and Ny, L., additional
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- 2019
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6. Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition
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Bradbury, K.E. Appleby, P.N. Tipper, S.J. Travis, R.C. Allen, N.E. Kvaskoff, M. Overvad, K. Tjønneland, A. Halkjær, J. Cervenka, I. Mahamat-Saleh, Y. Bonnet, F. Kaaks, R. Fortner, R.T. Boeing, H. Trichopoulou, A. La Vecchia, C. Stratigos, A.J. Palli, D. Grioni, S. Matullo, G. Panico, S. Tumino, R. Peeters, P.H. Bueno-de-Mesquita, H.B. Ghiasvand, R. Veierød, M.B. Weiderpass, E. Bonet, C. Molina, E. Huerta, J.M. Larrañaga, N. Barricarte, A. Merino, S. Isaksson, K. Stocks, T. Ljuslinder, I. Hemmingsson, O. Wareham, N. Khaw, K.-T. Gunter, M.J. Rinaldi, S. Tsilidis, K.K. Aune, D. Riboli, E. Key, T.J.
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Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma. © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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- 2019
7. Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition
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Leenders, M., Leufkens, A.M., Siersema, P.D., Duijnhoven, F.J.B. van, Vrieling, A., Hulshof, P.J., Gils, C.H. van, Overvad, K., Roswall, N., Kyro, C., Boutron-Ruault, M.C., Fagerhazzi, G., Cadeau, C., Kuhn, T., Johnson, T., Boeing, H., Aleksandrova, K., Trichopoulou, A., Klinaki, E., Androulidaki, A., Palli, D., Grioni, S., Sacerdote, C., Tumino, R., Panico, S., Bakker, M.F., Skeie, G., Weiderpass, E., Jakszyn, P., Barricarte, A., Huerta, J. Maria, Molina-Montes, E., Arguelles, M., Johansson, I., Ljuslinder, I., Key, T.J., Bradbury, K.E., Khaw, K.T., Wareham, N.J., Ferrari, P., Duarte-Salles, T., Jenab, M., Gunter, M.J., Vergnaud, A.C., Wark, P.A., Bueno-De-Mesquita, H.B., Leenders, M, Leufkens, Am, Siersema, Pd, van Duijnhoven, Fj, Vrieling, A, Hulshof, Pj, van Gils, Ch, Overvad, K, Roswall, N, Kyr?, C, Boutron Ruault, Mc, Fagerhazzi, G, Cadeau, C, K?hn, T, Johnson, T, Boeing, H, Aleksandrova, K, Trichopoulou, A, Klinaki, E, Androulidaki, A, Palli, D, Grioni, S, Sacerdote, C, Tumino, R, Panico, Salvatore, Bakker, Mf, Skeie, G, Weiderpass, E, Jakszyn, P, Barricarte, A, Mar?a Huerta, J, Molina Montes, E, Arg?elles, M, Johansson, I, Ljuslinder, I, Key, Tj, Bradbury, Ke, Khaw, Kt, Wareham, Nj, Ferrari, P, Duarte Salles, T, Jenab, M, Gunter, Mj, Vergnaud, Ac, Wark, Pa, Bueno de Mesquita, Hb, LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA2, and Risk Assessment of Toxic and Immunomodulatory Agents
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Adult ,Male ,Ascorbic Acid ,Antioxidants ,Fruits and vegetables ,Body Mass Index ,Risk Factors ,Surveys and Questionnaires ,Odds Ratio ,Humans ,Vitamin E ,Vitamin A ,Aged ,Rectal Neoplasms ,Incidence ,Vitamins ,Middle Aged ,Colorectal cancer ,Carotenoids ,Diet ,Europe ,Oxidative Stress ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Case-Control Studies ,Colonic Neoplasms ,Multivariate Analysis ,Female - Abstract
Item does not contain fulltext Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (alpha- and beta-carotene, canthaxanthin, beta-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (alpha-, beta- and gamma- and delta-tocopherol) and dietary consumption of beta-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary beta-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.
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- 2014
8. LBA71 - Phase II multicenter open label study of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study)
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Jespersen, H., Olofsson Bagge, R., Ullenhag, G., Carneiro, A., Helgadottir, H., Ljuslinder, I., Levin, M., All-Eriksson, C., Andersson, B., Stierner, U., Nilsson, L.M., Nilsson, J.A., and Ny, L.
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- 2019
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9. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort
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Hughes, D.J. Fedirko, V. Jenab, M. Schomburg, L. Méplan, C. Freisling, H. Bueno-De-Mesquita, H.B. Hybsier, S. Becker, N.-P. Czuban, M. Tjønneland, A. Outzen, M. Boutron-Ruault, M.-C. Racine, A. Bastide, N. Kühn, T. Kaaks, R. Trichopoulos, D. Trichopoulou, A. Lagiou, P. Panico, S. Peeters, P.H. Weiderpass, E. Skeie, G. Dagrun, E. Chirlaque, M.-D. Sánchez, M.-J. Ardanaz, E. Ljuslinder, I. Wennberg, M. Bradbury, K.E. Vineis, P. Naccarati, A. Palli, D. Boeing, H. Overvad, K. Dorronsoro, M. Jakszyn, P. Cross, A.J. Quirós, J.R. Stepien, M. Kong, S.Y. Duarte-Salles, T. Riboli, E. Hesketh, J.E.
- Abstract
Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μ/L and 4.3 mg/L in cases and 85.6 μ/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR=0.92, 95% CI: 0.82-1.03 per 25 lg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (ptrend=0.032; per 25 μ/L Se increase, IRR=0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend=0.009; per 0.806 mg/L increase, IRR50.89, 95% CI: 0.82-0.98) with the association more apparent in women (ptrend=0.004; IRR=0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (ptrend50.485; IRR50.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women. © 2014 UICC.
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- 2015
10. Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk - Results from the EPIC cohort study
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Dik, VK, Bueno-De-Mesquita, HB, Van Oijen, MGH, Siersema, PD, Uiterwaal, CSPM, Van Gils, CH, Van Duijnhoven, FJB, Cauchi, S, Yengo, L, Froguel, P, Overvad, K, Bech, BH, Tjønneland, A, Olsen, A, Boutron-Ruault, MC, Racine, A, Fagherazzi, G, Kühn, T, Campa, D, Boeing, H, Aleksandrova, K, Trichopoulou, A, Peppa, E, Oikonomou, E, Palli, D, Grioni, S, Vineis, P, Tumino, R, Panico, S, Peeters, PHM, Weiderpass, E, Engeset, D, Braaten, T, Dorronsoro, M, Chirlaque, MD, Sánchez, MJ, Barricarte, A, Zamora-Ros, R, Argüelles, M, Jirström, K, Wallström, P, Nilsson, LM, Ljuslinder, I, Travis, RC, Khaw, KT, Wareham, N, Freisling, H, Licaj, I, Jenab, M, Gunter, MJ, Murphy, N, Romaguera-Bosch, D, and Riboli, E
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Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7-±-8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. What's new? Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk. © 2013 UICC.
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- 2014
11. Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Nitter, M. Norgard, B. de Vogel, S. Eussen, S. J. P. M. and Meyer, K. Ulvik, A. Ueland, P. M. Nygard, O. Vollset, S. E. Bjorge, T. Tjonneland, A. Hansen, L. Boutron-Ruault, M. Racine, A. Cottet, V. Kaaks, R. Kuehn, T. and Trichopoulou, A. Bamia, C. Naska, A. Grioni, S. Palli, D. Panico, S. Tumino, R. Vineis, P. Bueno-de-Mesquita, H. B. van Kranen, H. Peeters, P. H. Weiderpass, E. and Dorronsoro, M. Jakszyn, P. Sanchez, M. Argueelles, M. and Huerta, J. M. Barricarte, A. Johansson, M. Ljuslinder, I. and Khaw, K. Wareham, N. Freisling, H. Duarte-Salles, T. and Stepien, M. Gunter, M. J. Riboli, E.
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Background: Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. Patients and methods: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations. Results: Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk. Conclusions: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.
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- 2014
12. LRIG1 amplification in breast cancer
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Ljuslinder, I., primary, Malmer, B., additional, Thomasson, M., additional, Golovleva, I., additional, Grankvist, K., additional, Höckenström, T., additional, Emdin, S., additional, Jonsson, Y., additional, Hedman, H., additional, and Henriksson, R., additional
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- 2004
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13. ALKYLRESORCINOLS (BIOMARKERS OF WHOLE-GRAIN INTAKE) AND RISK OF COLORECTAL CANCER IN THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION
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Kyro, C., Olsen, A., Landberg, R., Skeie, G., Loft, S., Aman, P., Leenders, M., Dik, V., Siersema, P., Pischon, T., Christensen, J., Overvad, K., Boutron-Ruault, M. C., Guy Fagherazzi, Cottet, V., Kuehn, T., Changclaude, J., Boeing, H., Trichopoulou, A., Bamia, C., Trichopoulos, D., Palli, D., Krogh, V., Tumino, R., Vineis, P., Panico, S., Peters, P., Weiderpass, E., Bakken, T., Asli, L., Argueelles, M., Jakszyn, P., Sanchez, M. J., Castano, J., Barricarte, A., Ljuslinder, I., Palmqvist, R., Key, T., Travis, R., Ferrari, P., Freisling, H., Jenab, M., Tjonneland, A., and Bueno-De-Mesquita, B.
14. Expression of verotoxin-1 receptor Gb3 in breast cancer tissue and verotoxin-1 signal transduction to apoptosis
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Johansson Anders, Brännström Thomas, Ljuslinder Ingrid, Moharer Jasmin, Kosovac Eldina, Johansson David, and Behnam-Motlagh Parviz
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The prerequisite for the potential use of the bacterial toxin verotoxin-1 in the treatment of breast cancer was investigated by first determining the expression of its receptor Gb3 (CD77) in clinical breast cancer tissue specimens. We then examined the cytotoxicity and mechanism of apoptosis induction of Escherichia coli verotoxin-1 (VT-1) in two human breast cancer cell lines. Methods Immunohistochemistry for Gb3 expression was performed on cryostat section from 25 breast cancer specimens. The human breast cancer cell lines T47D and MCF-7 were screened for Gb3 expression by flow cytometry. Fluorescein diacetate and LDH release was used to determine cell viability after VT-1 exposure. Apoptosis was studied by measuring caspase activity and DNA-fragmentation. Signal transduction studies were performed on T47D cells with immunoblotting. Results Gb3 expression was detected in the vascular endothelial cells of all tumours specimens, and in tumour cells in 17 of the specimens. We found no associations between tumour cell Gb3-expression and age, tumour size, TNM-classification, histological type, hormone receptor expression, or survival time. T47D cells strongly expressed Gb3 and were sensitive to the cytotoxicity, caspase activation and DNA fragmentation by VT-1, whereas MCF-7 cells with faint Gb3-expression were insensitive to VT-1. VT-1 (0.01 – 5 μg/L) exposure for 72 h resulted in a small percentage of viable T47D cells whereas the cytotoxicity of cells pre-treated with 2 μmol/L D, L-treo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP, an inhibitor of glucosylceramide synthesis) was eliminated (≤ 0.1 μg/L VT-1) or reduced (0.5 – 5 μg/L VT-1). VT-1 did not cause cellular LDH-release or cell cycle arrest. VT-1 induction of caspase-3 (0.1, 1, and 5 μg/L VT-1), -8, and -9 (1 and 5 μg/L VT-1) activity and DNA fragmentation of T47D cells was blocked by PPMP. Key components of MAP kinase signalling pathways that control mitochondrial function were investigated. VT-1 0.1 – 5 μg/L induced phosphorylation of JNK as well as MKK3/6 suggesting that survival signal pathways were overruled by VT-1-induced JNK activation leading to mitochondrial depolarization, caspase-9 activation and apoptosis. Conclusion The high specificity and apoptosis-inducing properties of verotoxin-1 indicates that the toxin potentially may be used for treatment of Gb3-expressing breast cancer.
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- 2009
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15. Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study
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Per Magne Ueland, Anne Tjønneland, Nicholas J. Wareham, Petra H.M. Peeters, Richard Palmqvist, Stein Emil Vollset, Marc J. Gunter, Kim Overvad, Miren Dorronsoro, Amanda J. Cross, Giovanna Masala, J. Ramón Quirós, Øivind Midttun, Krasimira Aleksandrova, Dimitrios Trichopoulos, Aurelio Barricarte, Yunxia Lu, Ruth C. Travis, Bas Bueno-de-Mesquita, Tilman Kuehn, Shu Chun Chuang, Claudia Agnoli, José María Huerta, Tobias Pischon, Martin Lajous, Heiner Boeing, Marie-Christine Boutron-Ruault, Pagona Lagiou, Antonia Trichopoulou, Guy Fagherazzi, Rosario Tumino, Rudolf Kaaks, Kay-Tee Khaw, Amalia Mattiello, Antonio Agudo, Esther Molina-Montes, Dagmar Drogan, Elisabete Weiderpass, Paolo Vineis, Elio Riboli, Ingrid Ljuslinder, University Medical Center Utrecht, Imperial College Trust, [Chuang,S] Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.[Chuang,S, Bueno-de-Mesquita,B, Peeter,PH, Gunter,M, Lu,Y, Cross,AJ, Riboli,E, Vineis,P] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Vollset,SE] Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. Division of Epidemiology, Norwegian Institute of Public Health, Bergen, Norway. [Midttun,O] Bevital AS, Bergen, Norway. [Ueland,PM] Department of Clinical Science, University of Bergen, Bergen, Norway. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway. [Bueno-de-Mesquita,B] The National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Lajous,M, Fagherazzi,G, Boutron-Ruault,M] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. University of Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Küehn,T] Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Drogan,D] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Tjønneland,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Oviedo, Spain. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Molina-Montes,E, Huerta,JM] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Travis,RC, Trichopoulou,A] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, ASP Ragusa, Italy. [Mattiello,A] Dipartamento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Palmqvist,R] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Aleksandrova,K] Nutrition, Immunity and Metabolism Start-up Lab, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany., The EPIC cohort is supported by the Europe Against Cancer Program of the European Commission (SANCO). The individual centers also received funding from: Denmark: Danish Cancer Society, France: Ligue centre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), Greece: the Hellenic Health Foundation, the Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity, Germany : German Cancer Aid, and Federal Ministry of Education and Research, Italy: Italian Association for Research on Cancer and the National Research Council, The Netherlands: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, Norway: Helga – Nordforsk centre of excellence in food, nutrition and health and The Norwegian Extra Foundation for Health and Rehabilitation, The Norwegian Cancer Society, Spain: Health Research Fund (FIS) of the Spanish Ministry of Health (Exp 96/0032, RETICC DR06/ 0020), the Spanish Regional Governments of Andalusia, Asturias, Basque Country, Murcia (N0 6236), and the Navarra and the Catalan Institute of Oncology, Sweden: Swedish Cancer Society, Swedish Scientific Council, and Regional Governments of Skane and Västerbotten, UK: Cancer Research UK and Medical Research Council. Grant supports for the biochemical measurements: HDL-C and TG were analysed with additional support from the Ministry of Public Health, Welfare and Sports, the Netherlands,German Cancer Aid, Federal Ministry for Education and Research, European Union, European Union and AIRC-ITALY , German Cancer Aid, Federal Ministry for Education and Research, European Union, Stavros Niarchos Foundation , Hellenic Ministry of Health, Hellenic Health Foundation, MRC and Cancer Research UK, and Hba1c was analysed with additional support from National Cancer Institute grant 1RO1CA102460 and data analyses on CRP were performed with support from World Cancer Research Fund International and Wereld Kanker Onderzoek Fonds (WCRF NL)
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0301 basic medicine ,Aging ,Síndrome metabòlica ,Geriatrics & Gerontology ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Methods::Research Design [Medical Subject Headings] ,030204 cardiovascular system & hematology ,Cardiovascular ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,immune system diseases ,GENETIC-VARIANTS ,Hyperlipidemia ,HORDALAND HEALTH ,Metabolic syndrome ,Cell-mediated immunity ,Neopterin ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes [Medical Subject Headings] ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,PROGNOSTIC VALUE ,Neopterina ,Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Lipid Metabolism Disorders::Dyslipidemias::Hyperlipidemias [Medical Subject Headings] ,1107 Immunology ,Biomarker (medicine) ,CORONARY-ARTERY-DISEASE ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Pteridines::Pterins::Biopterin::Neopterin [Medical Subject Headings] ,Life Sciences & Biomedicine ,SERUM NEOPTERIN ,medicine.medical_specialty ,Clinical Sciences ,Immunology ,Clinical nutrition ,Procesos Bioquímicos ,ADVERSE CARDIAC EVENTS ,03 medical and health sciences ,Clinical Research ,Internal medicine ,medicine ,Journal Article ,Nutrition ,COLORECTAL-CANCER RISK ,Cancer och onkologi ,Proyectos de Investigación ,Science & Technology ,INTERFERON-GAMMA ,business.industry ,Research ,1103 Clinical Sciences ,medicine.disease ,Ageing ,030104 developmental biology ,Blood pressure ,Endocrinology ,SYSTEM ACTIVATION ,chemistry ,Cardiovascular and Metabolic Diseases ,Cancer and Oncology ,Glycated hemoglobin ,Hiperlipidemias ,business ,Hiperlipèmia - Abstract
BACKGROUND: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC).RESULTS: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p CONCLUSIONS: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.
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- 2016
16. Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations
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Fedirko, Veronika, Romieu, Isabelle, Aleksandrova, Krasimira, Pischon, Tobias, Trichopoulos, Dimitrios, Peeters, Petra H, Romaguera-Bosch, Dora, Bueno-de-Mesquita, H Bas, Dahm, Christina C, Overvad, Kim, Chirlaque, Maria-Dolores, Johansen, Christoffer, Bidstrup, Pernille Envold Hansen, Dalton, Susanne Oksbjerg, Gunter, Marc J, Wark, Petra A, Norat, Teresa, Halkjaer, Jytte, Tjønneland, Anne, Dik, Vincent K, Siersema, Peter D, Boutron-Ruault, Marie-Christine, Dossus, Laure, Bastide, Nadia, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Trichopoulou, Antonia, Klinaki, Eleni, Katsoulis, Michalis, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Palli, Domenico, Vineis, Paolo, Weiderpass, Elisabete, Skeie, Guri, González, Carlos A, Sánchez, María-José, Barricarte, Aurelio, Amiano, Pilar, Quiros, J Ramon, Manjer, Jonas, Jirström, Karin, Ljuslinder, Ingrid, Palmqvist, Richard, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Stepien, Magdalena, Duarte-Salles, Talita, Riboli, Elio, Jenab, Mazda, Fedirko, V, Romieu, I, Aleksandrova, K, Pischon, T, Trichopoulos, D, Peeters, Ph, Romaguera Bosch, D, Bueno de Mesquita, Hb, Dahm, Cc, Overvad, K, Chirlaque, Md, Johansen, C, Bidstrup, Pe, Dalton, So, Gunter, Mj, Wark, Pa, Norat, T, Halkjaer, J, Tj?nneland, A, Dik, Vk, Siersema, Pd, Boutron Ruault, Mc, Dossus, L, Bastide, N, K?hn, T, Kaaks, R, Boeing, H, Trichopoulou, A, Klinaki, E, Katsoulis, M, Pala, V, Panico, Salvatore, Tumino, R, Palli, D, Vineis, P, Weiderpass, E, Skeie, G, Gonz?lez, Ca, S?nchez, Mj, Barricarte, A, Amiano, P, Quiros, Jr, Manjer, J, Jirstr?m, K, Ljuslinder, I, Palmqvist, R, Khaw, Kt, Wareham, N, Bradbury, Ke, Stepien, M, Duarte Salles, T, Riboli, E, and Jenab, M.
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Male ,Anthropometry ,Waist-Hip Ratio ,Incidence ,Adenocarcinoma ,Middle Aged ,Body Mass Index ,Europe ,Multivariate Analysis ,Humans ,Female ,Obesity ,Prospective Studies ,Sex Distribution ,Waist Circumference ,Colorectal Neoplasms ,Aged ,Proportional Hazards Models - Abstract
General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, pre-diagnostic BMI ≥30 kg/m(2) was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI
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- 2014
17. Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study
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Domenico Palli, Aurelio Barricarte, José Ramón Quirós, Laureen Dartois, Heather Ward, Salvatore Panico, Isabelle Romieu, Veronika Fedirko, Ulrika Ericson, Kim Overvad, Miren Dorronsoro, Pagona Lagiou, Krasimira Aleksandrova, Rudolf Kaaks, Kay-Tee Khaw, Anne Tjønneland, Elio Riboli, Laure Dossus, Sabina Rinaldi, Ingrid Ljuslinder, Genevieve Buckland, Marc J. Gunter, Petra H.M. Peeters, Vittorio Krogh, Alessio Naccarati, Ingegerd Johansson, Bodil Ohlsson, Peter D. Siersema, Kathryn E. Bradbury, Heiner Boeing, María José Sánchez, Mazda Jenab, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Elisabete Weiderpass, Guri Skeie, Kristin Benjaminsen Borch, Tobias Pischon, Sven Knüppel, Teresa Norat, Nicholas J. Wareham, Joyce Kong, Dora Romaguera, Kuanrong Li, Dimitrios Trichopoulos, Rosario Tumino, Marie-Christine Boutron-Ruault, María Dolores Chirlaque, [Aleksandrova,K, Knüppe,S, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Jenab,M, Fedirko,V, Rinald,S, Romieu,I, Kong,J] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands. [Bueno-de-Mesquita,HB, Norat,T, Romaguera,D, Peeters,PHM, Gunter,MJ, Ward,HA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Romaguera,D] Instituto de Investigacion Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Univ Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Li,K] Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Tjønneland,K] Diet, Genes and Environment Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Sánchez,MJ, Chirlaque,M] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Bradbury,KE] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'M.P.Arezzo' Hospital, Ragusa, Italy. [Naccarati,A] HuGeF - Human Genetics Foundation – Torino, Molecular and Genetic Epidemiology Unit, Turin, Italy. [Panico,S] Department of clinical and experimental medicine-Federico II University, Naples, Italy. [Peeters,PHM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherland. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Umeå University, Umeå, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital Malmö, Lund University, Malmö, Sweden. [Weiderpass,E, Skeie,G, Borch,KB] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland., The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l¿Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom)., Aleksandrova, Krasimira, Pischon, Tobia, Jenab, Mazda, Bueno de Mesquita, H. Ba, 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 Dolore, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nicholas J, Bradbury, Kathryn E, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Siersema, Peter D, Peeters, Petra H. M, Ljuslinder, Ingrid, Johansson, Ingegerd, Ericson, Ulrika, Ohlsson, Bodil, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Rinaldi, Sabina, Romieu, Isabelle, Kong, Joyce, Gunter, Marc J, Ward, Heather A, Riboli, Elio, and Boeing, Heiner
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Male ,consumo de alcohol ,Health Behavior ,0302 clinical medicine ,estudios prospectivos ,European Prospective Investigation into Cancer and ,Prospective Studies ,estudios de cohortes ,mediana edad ,PROPORTION ,anciano ,education.field_of_study ,VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801 ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings] ,dieta ,Incidence ,COLON-CANCER ,Hazard ratio ,lifestyle factors ,General Medicine ,adulto ,3. Good health ,estilo de vida ,030220 oncology & carcinogenesis ,Cohort ,acrylamide ,Dieta ,Cohort study ,Human ,medicine.medical_specialty ,Alcohol Drinking ,European Continental Ancestry Group ,Lifestyles ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings] ,European Prospective Investigation into Cancer and Nutrition (EPIC) ,Endocrinology and Diabetes ,dietary questionnaires ,haemoglobin adducts ,incidencia ,White People ,03 medical and health sciences ,Càncer colorectal ,population attributable risks ,Humans ,education ,Life Style ,METAANALYSIS ,Aged ,Cancer och onkologi ,Science & Technology ,Proportional hazards model ,VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 ,biomarkers ,Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings] ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings] ,PREVENTION ,Prospective Studie ,MYOCARDIAL-INFARCTION ,ATTRIBUTABLE RISK ,Cardiovascular and Metabolic Diseases ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings] ,Cancer and Oncology ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings] ,RISK-FACTORS ,Proportional Hazards Model ,grupo de ascendencia continental europea ,measurement errors ,Gerontology ,colorectal cancer ,combined impact ,modelos de riesgos proporcionales ,humanos ,Colorectal Neoplasm ,Cohort Studies ,Risk Factors ,Neoplasias colorrectales ,Hábito de fumar ,030212 general & internal medicine ,Prospective cohort study ,conducta sanitaria ,Medicine(all) ,Consumo de alcohol ,Public Health, Global Health, Social Medicine and Epidemiology ,Middle Aged ,European Prospective Investigation into Cancer and Nutrition ,Europe ,NUTRITION ,Female ,Colorectal Neoplasms ,Life Sciences & Biomedicine ,Research Article ,Adult ,Estils de vida ,neoplasias colorrectales ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings] ,Population ,Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings] ,smoking ,Medicine, General & Internal ,General & Internal Medicine ,Internal medicine ,medicine ,factores de riesgo ,Proportional Hazards Models ,Nutrition (EPIC) ,RECTAL CANCERS ,business.industry ,Risk Factor ,Diet ,VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762 ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,PHYSICAL-ACTIVITY ,Attributable risk ,Cohort Studie ,VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801 ,business - Abstract
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, The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom).
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- 2014
18. 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)
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Anne Tjønneland, Christina Bamia, Aurelio Barricarte, Laure Dossus, Petra H.M. Peeters, Marc J. Gunter, Sabine Westhpal, Antonia Trichopoulou, Sabina Rinaldi, Ruth C. Travis, Veronika Fedirko, Fränzel J.B. Van Duijnhoven, J. Ramón Quirós, Kay-Tee Khaw, Philippos Orfanos, Rudolf Kaaks, Krasimira Aleksandrova, Richard Palmqvist, Neil Murphy, Esther Molina-Montes, Eric J. Duell, Eugene Jansen, Jytte Halkjær, Nicholas J. Wareham, Tobias Pischon, Mazda Jenab, Antoine Racine, María Dolores Chirlaque, Domenico Palli, Claudia Agnoli, Miren Dorronsoro, Pietro Ferrari, Heiner Boeing, Kim Overvad, Rosario Tumino, Elio Riboli, Ingrid Ljuslinder, Marie-Christine Boutron-Ruault, Salvatore Panico, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Isabelle Romieu, Paolo Vineis, Aleksandrova, K, Jenab, M, Bueno de Mesquita, Hb, Fedirko, V, Kaaks, R, Lukanova, A, van Duijnhoven, Fj, Jansen, E, Rinaldi, S, Romieu, I, Ferrari, P, Murphy, N, Gunter, Mj, Riboli, E, Westhpal, S, Overvad, K, Tj?nneland, A, Halkj?r, J, Boutron Ruault, Mc, Dossus, L, Racine, A, Trichopoulou, A, Bamia, C, Orfanos, P, Agnoli, C, Palli, D, Panico, Salvatore, Tumino, R, Vineis, P, Peeters, Ph, Duell, Ej, Molina Montes, E, Quir?s, Jr, Dorronsoro, M, Chirlaque, Md, Barricarte, A, Ljuslinder, I, Palmqvist, R, Travis, Rc, Khaw, Kt, Wareham, N, Pischon, T, and Boeing, H.
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Oncology ,Male ,Nutrition and Disease ,multiple imputation ,Epidemiology ,hdl-cholesterol ,Rate ratio ,adipose-tissue ,Body Mass Index ,chemistry.chemical_compound ,c-reactive protein ,Risk Factors ,Voeding en Ziekte ,plasma adiponectin ,oxidative stress ,Prospective Studies ,Prospective cohort study ,Incidence ,density-lipoprotein cholesterol ,Middle Aged ,Prognosis ,European Prospective Investigation into Cancer and Nutrition ,Europe ,C-Reactive Protein ,Biomarker (medicine) ,Female ,Colorectal Neoplasms ,Metabolic Networks and Pathways ,medicine.medical_specialty ,binding-proteins ,insulin-resistance ,soluble leptin receptor ,Adipokines ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Triglycerides ,VLAG ,Aged ,Glycated Hemoglobin ,Inflammation ,Leptin receptor ,Adiponectin ,business.industry ,Case-control study ,Endocrinology ,Logistic Models ,chemistry ,Socioeconomic Factors ,Case-Control Studies ,Glycated hemoglobin ,business - Abstract
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 multi-variable-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. © Springer Science+Business Media 2014.
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- 2013
19. Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer
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Kyrø, Cecilie, Olsen, Anja, Landberg, Rikard, Skeie, Guri, Loft, Steffen, Åman, Per, Leenders, Max, Dik, Vincent K., Siersema, Peter D., Pischon, Tobias, Christensen, Jane, Overvad, Kim, Boutron-Ruault, Marie Christine, Fagherazzi, Guy, Cottet, Vanessa, Kühn, Tilman, Chang-Claude, Jenny, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Trichopoulos, Dimitrios, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Peeters, Petra H., Weiderpass, Elisabete, Bakken, Toril, Åsli, Lene Angell, Argüelles, Marcial, Jakszyn, Paula, Sánchez, María José, Amiano, Pilar, Huerta, José María, Barricarte, Aurelio, Ljuslinder, Ingrid, Palmqvist, Richard, Khaw, Kay Tee, Wareham, Nick, Key, Timothy J., Travis, Ruth C., Ferrari, Pietro, Freisling, Heinz, Jenab, Mazda, Gunter, Marc J., Murphy, Neil, Riboli, Eilo, Tjønneland, Anne, Bueno-De-Mesquita, H. B., LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, Risk Assessment of Toxic and Immunomodulatory Agents, Kyr?, C, Olsen, A, Landberg, R, Skeie, G, Loft, S, Aman, P, Leenders, M, Dik, Vk, Siersema, Pd, Pischon, T, Christensen, J, Overvad, K, Boutron Ruault, Mc, Fagherazzi, G, Cottet, V, K?hn, T, Chang Claude, J, Boeing, H, Trichopoulou, A, Bamia, C, Trichopoulos, D, Palli, D, Krogh, V, Tumino, R, Vineis, P, Panico, Salvatore, Peeters, Ph, Weiderpass, E, Bakken, T, Asli, La, Arg?elles, M, Jakszyn, P, S?nchez, Mj, Amiano, P, Huerta, Jm, Barricarte, A, Ljuslinder, I, Palmqvist, R, Khaw, Kt, Wareham, N, Key, Tj, Travis, Rc, Ferrari, P, Freisling, H, Jenab, M, Gunter, Mj, Murphy, N, Riboli, E, Tj?nneland, A, Bueno de Mesquita, Hb, LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, and Risk Assessment of Toxic and Immunomodulatory Agents
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Male ,medicine.medical_specialty ,Pathology ,Cancer Research ,Colorectal cancer ,Scandinavian and Nordic Countries ,Rate ratio ,Gastroenterology ,Body Mass Index ,Alkylresorcinol ,Risk Factors ,Internal medicine ,Odds Ratio ,Medicine ,Humans ,Triticum ,Aged ,Cancer och onkologi ,business.industry ,Mediterranean Region ,Incidence (epidemiology) ,Incidence ,Secale ,Case-control study ,food and beverages ,Cancer ,Odds ratio ,Feeding Behavior ,Resorcinols ,Middle Aged ,medicine.disease ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Europe ,Logistic Models ,Oncology ,Cardiovascular and Metabolic Diseases ,Cancer and Oncology ,Case-Control Studies ,Female ,business ,Colorectal Neoplasms ,Biomarkers - Abstract
Background Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. Methods The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. Results High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). Conclusions High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.
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- 2013
20. Mediterranean diet and colorectal cancer risk: results from a European cohort
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Timothy J. Key, Domenico Palli, Isabelle Romieu, Brian Buijsse, Alessio Naccarati, Veronika Fedirko, Pagona Lagiou, Miren Dorronsoro, Kay-Tee Khaw, Richard Palmqvist, Petra H.M. Peeters, Fränzel J.B. Van Duijnhoven, Anja Olsen, Eiliv Lund, Guri Skeie, Christina C. Dahm, Christina Bamia, Anne Tjønneland, Sara Grioni, Sophie Morois, Claudia Agnoli, Kim Overvad, Dimitrios Trichopoulos, George Adarakis, Dagrun Engeset, Nicholas J. Wareham, Verena A. Grote, Antonia Trichopoulou, Dora Romaguera, Rosario Tumino, María José Sánchez, Heiner Boeing, Genevieve Buckland, Salvatore Panico, Vanessa Cottet, Birgit Teucher, Aurelio Barricarte, Mazda Jenab, J. Ramón Quirós, Isabel Drake, José María Huerta, H. Bas Bueno-de-Mesquita, Teresa Norat, Marie-Christine Boutron-Ruault, Aliki J. Taylor, Ingrid Ljuslinder, Bamia, C, Lagiou, P, Buckland, G, Grioni, S, Agnoli, C, Taylor, Aj, Dahm, Cc, Overvad, K, Olsen, A, Tj?nneland, A, Cottet, V, Boutron Ruault, Mc, Morois, S, Grote, V, Teucher, B, Boeing, H, Buijsse, B, Trichopoulos, D, Adarakis, G, Tumino, R, Naccarati, A, Panico, Salvatore, Palli, D, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Peeters, Ph, Engeset, D, Skeie, G, Lund, E, S?nchez, Mj, Barricarte, A, Huerta, Jm, Quir?s, Jr, Dorronsoro, M, Ljuslinder, I, Palmqvist, R, Drake, I, Key, Tj, Khaw, Kt, Wareham, N, Romieu, I, Fedirko, V, Jenab, M, Romaguera, D, Norat, T, and Trichopoulou, A.
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Gerontology ,Mediterranean diet ,Nutrition and Disease ,Epidemiology ,population ,Diet, Mediterranean ,0302 clinical medicine ,Risk Factors ,Surveys and Questionnaires ,Voeding en Ziekte ,Medicine ,Prospective Studies ,030212 general & internal medicine ,adherence ,Prospective cohort study ,physical-activity ,education.field_of_study ,Incidence ,Hazard ratio ,health ,Middle Aged ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Europe ,nutrition ,030220 oncology & carcinogenesis ,Cohort ,Female ,epic cohort ,Colorectal Neoplasms ,Cohort study ,metaanalysis ,Adult ,Population ,survival ,White People ,03 medical and health sciences ,rectal cancers ,Confidence Intervals ,Humans ,patterns ,Sex Distribution ,education ,Aged ,Proportional Hazards Models ,VLAG ,business.industry ,Proportional hazards model ,Socioeconomic Factors ,business ,Follow-Up Studies ,Demography - Abstract
The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6-9) with the lowest (scores 0-3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk.
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- 2013
21. Prognostic genome and transcriptome signatures in colorectal cancers.
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Nunes L, Li F, Wu M, Luo T, Hammarström K, Torell E, Ljuslinder I, Mezheyeuski A, Edqvist PH, Löfgren-Burström A, Zingmark C, Edin S, Larsson C, Mathot L, Osterman E, Osterlund E, Ljungström V, Neves I, Yacoub N, Guðnadóttir U, Birgisson H, Enblad M, Ponten F, Palmqvist R, Xu X, Uhlén M, Wu K, Glimelius B, Lin C, and Sjöblom T
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- Humans, Prognosis, Genome, Human genetics, DNA Copy Number Variations genetics, Male, Female, Cohort Studies, Stromal Cells metabolism, Stromal Cells pathology, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms mortality, Transcriptome genetics, Mutation, Gene Expression Profiling, Microsatellite Instability, Gene Expression Regulation, Neoplastic
- Abstract
Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways
1 . Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24 had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFβ pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy., (© 2024. The Author(s).)- Published
- 2024
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22. Survival and Quality of Life after Isolated Hepatic Perfusion with Melphalan as a Treatment for Uveal Melanoma Liver Metastases - Final Results from the Phase III Randomized Controlled Trial SCANDIUM.
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Olofsson Bagge R, Nelson A, Shafazand A, All-Eriksson C, Cahlin C, Elander N, Gustavsson A, Helgadottir H, Kiilgaard JF, Kinhult S, Ljuslinder I, Mattsson J, Rizell M, Sternby Eilard M, Ullenhag GJ, Nilsson JA, Ny L, and Lindnér P
- Abstract
Objective: To investigate overall survival (OS) and health-related quality of life (HRQOL) of first-line isolated hepatic perfusion (IHP) compared to best alternative care (BAC) for patients with uveal melanoma liver metastases., Summary Background Data: Approximately half of patients with uveal melanoma develop metastatic disease, most commonly in the liver and systemic treatment options are limited. Isolated hepatic perfusion (IHP) is a locoregional therapy with high response rates but with unclear effect on overall survival (OS)., Methods: In this phase III randomized controlled multicenter trial (the SCANDIUM trial) patients with previously untreated isolated uveal melanoma liver metastases were included between 2013-2021, with at least 24 months of follow-up. The planned accrual was 90 patients randomized 1:1 to receive a one-time treatment with IHP or BAC. Crossover to IHP was not allowed. The primary endpoint was the 24-month OS rate, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. HRQOL was measured by the EuroQol 5-domains 3-levels (EQ-5D-3L) questionnaire over 12 months., Results: The intention-to-treat (ITT) population included 87 patients randomized to the IHP group (43 patients; 41 [89%] received IHP) or the control group (44 patients). The control group received chemotherapy (49%), immunotherapy (39%), or localized interventions (9%). In the ITT population, the median PFS was 7.4 months in the IHP group compared with 3.3 months in the control group, with a hazard ratio of 0.21 (95% CI, 0.12-0.36). The 24-month OS rate was 46.5% in the IHP group versus 29.5% in the control group (P=0.12). The median OS was 21.7 months versus 17.6 months, with a hazard ratio of 0.64 (95% CI, 0.37-1.10). EQ-5D-3L showed a sustained high health status for the IHP group over 12 months, compared to a deteriorating trend in the control group., Conclusions: For patients with liver metastases from uveal melanoma, IHP offers high response rates translating to a benefit in PFS including a trend of better HRQOL compared to the control group. However, the primary endpoint of OS at 24 months was not met., Competing Interests: CONFLICT OF INTEREST: ROB has received institutional research grants from Bristol-Myers Squibb (BMS) and SkyLineDx, speaker honoraria from Roche and Pfizer, and has served on advisory boards for Amgen, BD/BARD, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Roche and Sanofi Genzyme, and is a shareholder in SATMEG Ventures AB. LN has received institutional research grants from Merck and Syndax Pharmaceuticals, speaker honoraria from BMS, Johnson&Johnson, Leo Pharma, MSD, Novartis, and Pfizer, has served on advisory boards for BMS, MSD, Novartis, Pierre Fabre, Sanofi Genzyme, and Zealth, and is a shareholder in SATMEG Ventures AB. HH has received speaker honoraria from BMS, MSD, and Pierre Fabre and has served on advisory boards for MSD and Novartis. ILJ has served on advisory boards for MSD and BMS. JN is a shareholder in SATMEG Ventures AB. GU has during the past two years received honoraria for teaching activities by BMS, MSD, Pierre Fabre, and Novartis and for consulting/advising by Incyte, BMS, Novartis, MSD, Alligator Bioscience, LIDDS, and SeqCure Immunology AB and is a stock owner in ESSITY and Oncopeptides. PL has served on advisory boards for Pierre Fabre, (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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23. Opposing roles by KRAS and BRAF mutation on immune cell infiltration in colorectal cancer - possible implications for immunotherapy.
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Edin S, Gylling B, Li X, Stenberg Å, Löfgren-Burström A, Zingmark C, van Guelpen B, Ljuslinder I, Ling A, and Palmqvist R
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- Humans, Immunotherapy, Microsatellite Instability, Mutation, Prognosis, Proto-Oncogene Proteins p21(ras) genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms therapy, Colorectal Neoplasms pathology, Proto-Oncogene Proteins B-raf genetics, Lymphocytes, Tumor-Infiltrating metabolism
- Abstract
Background: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC., Methods: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8
+ ), Th1 cells (T-bet+ ), T regulatory cells (FoxP3+ ), B cells (CD20+ ), and macrophages (CD68+ ) in a cohort of 257 CRC patients., Results: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts., Conclusion: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC., (© 2023. The Author(s).)- Published
- 2024
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24. Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial).
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Olofsson Bagge R, Nelson A, Shafazand A, All-Eriksson C, Cahlin C, Elander N, Helgadottir H, Kiilgaard JF, Kinhult S, Ljuslinder I, Mattsson J, Rizell M, Sternby Eilard M, Ullenhag GJ, Nilsson JA, Ny L, and Lindnér P
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- Humans, Scandium therapeutic use, Prospective Studies, Chemotherapy, Cancer, Regional Perfusion adverse effects, Chemotherapy, Cancer, Regional Perfusion methods, Perfusion, Melphalan, Liver Neoplasms therapy
- Abstract
Purpose: About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking., Methods: In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety., Results: Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively ( P < .0001). The median PFS was 7.4 months versus 3.3 months ( P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months ( P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group., Conclusion: IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
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- 2023
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25. Porphyromonas gingivalis in Colorectal Cancer and its Association to Patient Prognosis.
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Kerdreux M, Edin S, Löwenmark T, Bronnec V, Löfgren-Burström A, Zingmark C, Ljuslinder I, Palmqvist R, and Ling A
- Abstract
Microbiota dysbiosis may affect both the development and progression of colorectal cancer (CRC). Large metagenomic studies have highlighted specific oral bacteria linked to CRC including Porphyromonas gingivalis . Few studies have however analysed the implications of this bacterium in CRC progression and survival. In this study, we investigated the intestinal presence of P. gingivalis by qPCR in both faecal and mucosal samples from two different patient cohorts, including patients with precancerous dysplasia or CRC, as well as controls. P. gingivalis was detected in 2.6-5.3% of CRC patients and significantly different levels of P. gingivalis were found in faeces of CRC patients compared to controls ( P = 0.028). Furthermore, an association was found between the presence of P. gingivalis in faeces and tumour tissue ( P < 0.001). Our findings further suggested a potential link between mucosal P. gingivalis and tumours of MSI subtype ( P = 0.040). Last but not least, patients with faecal P. gingivalis were found to have a significantly decreased cancer-specific survival ( P = 0.040). In conclusion, P. gingivalis could be linked to patients with CRC and to a worse patient prognosis. Further studies are needed to elucidate the role of P. gingivalis in CRC pathogenesis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
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- 2023
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26. Defunctioning stoma before neoadjuvant treatment or resection of endoscopically obstructing rectal cancer.
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Sandén G, Svensson J, Ljuslinder I, and Rutegård M
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- Humans, Neoadjuvant Therapy, Retrospective Studies, Anastomosis, Surgical adverse effects, Surgical Stomas adverse effects, Rectal Neoplasms complications, Rectal Neoplasms surgery
- Abstract
Aim: To investigate whether patients with endoscopically untraversable rectal cancer may benefit from a defunctioning stoma created before neoadjuvant therapy or resectional surgery., Methods: This retrospective study comprise patients diagnosed with rectal cancer during 2007-2020 in Region Västerbotten, Sweden. The primary outcome was time between diagnosis and any treatment, while survival and the incidence of complications were secondary outcomes. Excluded were patients without endoscopic obstruction, patients already having a stoma, patients with recurrent disease, palliative patients, and patients receiving a stoma shortly after diagnosis due to any urgent bowel-related complication. Data were obtained from the Swedish Colorectal Cancer Registry and medical records. Kaplan-Meier failure curves were drawn, and a multivariable Cox regression model was employed for confounding adjustment., Results: Out of 843 patients, 57 remained after applying exclusion criteria. Some 12/57 (21%) patients received a planned stoma before treatment, and the remainder received upfront neoadjuvant therapy or surgery. Median time to any treatment was 51 days for the planned stoma group and 36 days for the control group, with an adjusted hazard ratio of 0.28 (95% confidence interval: 0.12-0.64). Complications occurred at a rate of 5/12 (42%) and 7/45 (16%) in the planned stoma group and control group, respectively. Survival was similar between groups., Conclusion: A planned stoma results in treatment delay, but it remains unclear whether this is clinically relevant. Complications were more common in the planned stoma group, although the data are limited. While larger studies are needed, it seems feasible to avoid defunctioning stomas even in endoscopically obstructing rectal cancers., (© 2023. The Author(s).)
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- 2023
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27. Tumour Colonisation of Parvimonas micra Is Associated with Decreased Survival in Colorectal Cancer Patients.
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Löwenmark T, Löfgren-Burström A, Zingmark C, Ljuslinder I, Dahlberg M, Edin S, and Palmqvist R
- Abstract
Increasing evidence suggests that the gut microbiota may impact colorectal cancer (CRC) development and progression. In this study, the tumour colonisation of two CRC-associated bacteria, Parvimonas micra and Fusobacterium nucleatum , was studied in relation to patient survival in a cohort of 257 CRC patients. Colonisation of P. micra and F. nucleatum was analysed in fresh frozen tumour tissue (n = 112) and in faeces (n = 250) by qPCR. When analysing tumour tissues, both P. micra and F. nucleatum were found to be associated with decreased five-year cancer-specific survival, an association that remained significant in multivariable analysis for P. micra . Furthermore, we found significant associations of high levels of P. micra and F. nucleatum with tumour molecular characteristics, i.e., tumours mutated in BRAF
V600E , and tumours of the MSI subtype. The analysis of faecal samples showed weaker associations with prognosis and tumour molecular characteristics. In conclusion, our findings support a novel association of tumour colonisation of P. micra with decreased patient survival. A better understanding of the role of the gut microbiota in CRC might contribute to the advancement of prognostic tools and new targets for therapy., Competing Interests: The authors declare no conflict of interest.- Published
- 2022
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28. Parvimonas micra is associated with tumour immune profiles in molecular subtypes of colorectal cancer.
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Löwenmark T, Li X, Löfgren-Burström A, Zingmark C, Ling A, Kellgren TG, Larsson P, Ljuslinder I, Wai SN, Edin S, and Palmqvist R
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- Firmicutes, Fusobacterium nucleatum, Humans, Microsatellite Instability, Colorectal Neoplasms
- Abstract
The importance of the tumour microbiome in different aspects of colorectal cancer (CRC) has been increasingly recognised, but many questions remain. The aim of this study was to explore the effect of specific CRC associated microbes on the tumour immune response, which has a considerable prognostic value in CRC. We applied specific qPCR to detect Parvimonas micra and Fusobacterium nucleatum in tumour tissues from an immunologically well-characterised cohort of 69 CRC patients. This cohort included detailed analyses of immune profiles based on flow cytometry and transcriptomics in tumour tissue and blood, along with comprehensive analyses of molecular subtypes. P. micra and F. nucleatum were detected in 24% and 64% of tumour tissues, respectively. We found a significant association of P. micra with high-grade tumours and tumours of CMS1 subtype. F. nucleatum was significantly associated with right-sided tumours, microsatellite instability, and CMS1 tumours. The immunological analyses revealed significant associations of P. micra with activated CD69
+ T lymphocytes and increased antigen-presenting HLA-DR+ B lymphocytes. P. micra was also positively associated with M1 and M2 macrophage traits. The impact of P. micra tumour colonisation on the immune response was further assessed using transcriptomics in validation of our findings. No associations were found between F. nucleatum and immune profiles in this study. Our findings support novel associations between P. micra and the immune response in CRC. A better understanding of these interactions might help to identify important predictive and prognostic tools as well as new targets for therapy., (© 2022. The Author(s).)- Published
- 2022
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29. Type IV Collagen in Human Colorectal Liver Metastases-Cellular Origin and a Circulating Biomarker.
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Lindgren M, Rask G, Jonsson J, Berglund A, Lundin C, Jonsson P, Ljuslinder I, and Nyström H
- Abstract
Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM.
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- 2022
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30. The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma.
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Ny L, Jespersen H, Karlsson J, Alsén S, Filges S, All-Eriksson C, Andersson B, Carneiro A, Helgadottir H, Levin M, Ljuslinder I, Olofsson Bagge R, Sah VR, Stierner U, Ståhlberg A, Ullenhag G, Nilsson LM, and Nilsson JA
- Subjects
- Humans, Melanoma pathology, Progression-Free Survival, Tumor Suppressor Proteins genetics, Ubiquitin Thiolesterase genetics, Uveal Neoplasms pathology, Antibodies, Monoclonal, Humanized administration & dosage, Benzamides administration & dosage, Melanoma drug therapy, Pyridines administration & dosage, Uveal Neoplasms drug therapy
- Abstract
Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.Trial registration ClinicalTrials.gov registration number: NCT02697630 (registered 3 March 2016). EudraCT registration number: 2016-002114-50., (© 2021. The Author(s).)
- Published
- 2021
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31. A modified protein marker panel to identify four consensus molecular subtypes in colorectal cancer using immunohistochemistry.
- Author
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Li X, Larsson P, Ljuslinder I, Ling A, Löfgren-Burström A, Zingmark C, Edin S, and Palmqvist R
- Subjects
- Aged, Aged, 80 and over, Biomarkers, Tumor genetics, CDX2 Transcription Factor analysis, Colorectal Neoplasms classification, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Cytoskeletal Proteins analysis, Female, Gene Expression Profiling, Humans, Male, Membrane Proteins analysis, Middle Aged, Predictive Value of Tests, Receptor, Serotonin, 5-HT2B analysis, Reproducibility of Results, Sequence Analysis, RNA, Transcriptome, Wnt Signaling Pathway, Zinc Finger E-box-Binding Homeobox 1 analysis, beta Catenin analysis, Biomarkers, Tumor analysis, Colorectal Neoplasms chemistry, Immunohistochemistry
- Abstract
Colorectal cancer (CRC) is a heterogeneous disease with different genetic and molecular backgrounds, leading to a diverse patient prognosis and treatment response. Four consensus molecular subtypes (CMS 1-4) have recently been proposed based on transcriptome profiling. A clinically practical immunohistochemistry (IHC) based CMS classifier consisting of the four markers FRMD6, ZEB1, HTR2B, and CDX2 was then demonstrated. However, the IHC-CMS classifier did not distinguish between CMS2 and CMS3 tumours. In this study, we have applied the proposed transcriptome based and IHC-based CMS classifiers in a CRC cohort of 65 patients and found a concordance of 77.5 %. Further, we modified the IHC-CMS classifier by analysing the differentially expressed genes between CMS2 and CMS3 tumours using RNA-sequencing data from the TCGA dataset. The result showed that WNT signalling was among the most upregulated pathways in CMS2 tumours, and the expression level of CTNNB1 (encoding β-catenin), a WNT pathway hallmark, was significantly upregulated (P = 1.15 × 10
-6 ). We therefore introduced nuclear β-catenin staining to the IHC-CMS classifier. Using the modified classifier in our cohort, we found a 71.4 % concordance between the IHC and RNA-sequencing based CMS classifiers. Moreover, β-catenin staining could classify 16 out of the 19 CMS2/3 tumours into CMS2 or CMS3, thereby showing an 84.2 % concordance with the RNA-sequencing-based classifier. In conclusion, we evaluated CMS classifiers based on transcriptome and IHC analysis. We present a modified IHC panel that categorizes CRC tumours into the four CMS groups. To our knowledge, this is the first study using IHC to identify all four CMS groups., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)- Published
- 2021
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32. A Detailed Flow Cytometric Analysis of Immune Activity Profiles in Molecular Subtypes of Colorectal Cancer.
- Author
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Li X, Ling A, Kellgren TG, Lundholm M, Löfgren-Burström A, Zingmark C, Rutegård M, Ljuslinder I, Palmqvist R, and Edin S
- Abstract
The local anti-tumour immune response has important prognostic value in colorectal cancer (CRC). In the era of immunotherapy, a better understanding of the immune response in molecular subgroups of CRC may lead to significant advances in personalised medicine. On this note, microsatellite instable (MSI) tumours have been characterised by increased immune infiltration, suggesting MSI as a marker for immune inhibitor checkpoint therapy. Here, we used flow cytometry to perform a comprehensive analysis of immune activity profiles in tumour tissues, adjacent non-malignant tissues and blood, from a cohort of 69 CRC patients. We found several signs of immune suppression in tumours compared to adjacent non-malignant tissues, including T cells more often expressing the immune checkpoint molecules programmed cell death protein (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). We further analysed immune cell infiltration in molecular subgroups of CRC. MSI tumours were indeed found to be associated with increased immune infiltration, including increased fractions of PD-1
+ T cells. No correlation was, however, found between MSI and the fraction of CTLA-4+ T cells. Interestingly, within the group of patients with microsatellite stable (MSS) tumours, some also presented with increased immune infiltration, including comparably high portions of PD-1+ T cells, but also CTLA-4+ T cells. Furthermore, no correlation was found between PD-1+ and CTLA-4+ T cells, suggesting that different tumours may, to some extent, be regulated by different immune checkpoints. We further evaluated the distribution of immune activity profiles in the consensus molecular subtypes of CRC. In conclusion, our findings suggest that different immune checkpoint inhibitors may be beneficial for selected CRC patients irrespective of MSI status. Improved predictive tools are required to identify these patients.- Published
- 2020
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33. Rectal cancer: a methodological approach to matching PET/MRI to histopathology.
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Rutegård MK, Båtsman M, Blomqvist L, Rutegård M, Axelsson J, Ljuslinder I, Rutegård J, Palmqvist R, Brännström F, Brynolfsson P, and Riklund K
- Subjects
- Adult, Aged, Female, Humans, Lymphatic Metastasis diagnostic imaging, Lymphatic Metastasis pathology, Magnetic Resonance Imaging standards, Male, Middle Aged, Multimodal Imaging standards, Neoplasm Staging, Positron-Emission Tomography standards, Rectal Neoplasms pathology, Magnetic Resonance Imaging methods, Multimodal Imaging methods, Positron-Emission Tomography methods, Rectal Neoplasms diagnostic imaging
- Abstract
Purpose: To enable the evaluation of locoregional disease in the on-going RECTOPET (REctal Cancer Trial on PET/MRI/CT) study; a methodology to match mesorectal imaging findings to histopathology is presented, along with initial observations., Methods: FDG-PET/MRI examinations were performed in twenty-four consecutively included patients with rectal adenocarcinoma. In nine patients, of whom five received neoadjuvant treatment, a postoperative MRI of the surgical specimen was performed. The pathological cut-out was performed according to clinical routine with the addition of photo documentation of each slice of the surgical specimen, meticulously marking the location, size, and type of pathology of each mesorectal finding. This allowed matching individual nodal structures from preoperative MRI, via the specimen MRI, to histopathology., Results: Preoperative MRI identified 197 mesorectal nodal structures, of which 92 (47%) could be anatomically matched to histopathology. Of the matched nodal structures identified in both MRI and histopathology, 25% were found to be malignant. These malignant structures consisted of lymph nodes (43%), tumour deposits (48%), and extramural venous invasion (9%). One hundred eleven nodal structures (55%) could not be matched anatomically. Of these, 97 (87%) were benign lymph nodes, and 14 (13%) were malignant nodal structures. Five were malignant lymph nodes, and nine were tumour deposits, all of which had a short axis diameter < 5 mm., Conclusions: We designed a method able to anatomically match and study the characteristics of individual mesorectal nodal structures, enabling further research on the impact of each imaging modality. Initial observations suggest that small malignant nodal structures assessed as lymph nodes in MRI often comprise other forms of mesorectal tumour spread., Trial Registration: Clinical Trials Identifier: NCT03846882 .
- Published
- 2020
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34. Parvimonas micra as a putative non-invasive faecal biomarker for colorectal cancer.
- Author
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Löwenmark T, Löfgren-Burström A, Zingmark C, Eklöf V, Dahlberg M, Wai SN, Larsson P, Ljuslinder I, Edin S, and Palmqvist R
- Subjects
- Aged, Aged, 80 and over, Bacterial Load, Biomarkers, Tumor genetics, Biomarkers, Tumor isolation & purification, Case-Control Studies, Cohort Studies, Colonoscopy, Early Detection of Cancer methods, Feces microbiology, Female, Firmicutes genetics, Fusobacterium nucleatum genetics, Fusobacterium nucleatum isolation & purification, Humans, Male, Middle Aged, Risk Factors, Colorectal Neoplasms diagnosis, Colorectal Neoplasms microbiology, Firmicutes isolation & purification, Gastrointestinal Microbiome genetics
- Abstract
The use of faecal microbial markers as non-invasive biomarkers for colorectal cancer (CRC) has been suggested, but not fully elucidated. Here, we have evaluated the importance of Parvimonas micra as a potential non-invasive faecal biomarker in CRC and its relation to other microbial biomarkers. The levels of P. micra, F. nucleatum and clbA + bacteria were quantified using qPCR in faecal samples from a population-based cohort of patients undergoing colonoscopy due to symptoms from the large bowel. The study included 38 CRC patients, 128 patients with dysplasia and 63 controls. The results were validated in a second consecutive CRC cohort including faecal samples from 238 CRC patients and 94 controls. We found significantly higher levels of P. micra in faecal samples from CRC patients compared to controls. A test for P. micra could detect CRC with a specificity of 87.3% and a sensitivity of 60.5%. In addition, we found that combining P. micra with other microbial markers, could further enhance test sensitivity. Our findings support the potential use of P. micra as a non-invasive biomarker for CRC. Together with other microbial faecal markers, P. micra may identify patients with "high risk" microbial patterns, indicating increased risk and incidence of cancer.
- Published
- 2020
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35. Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition.
- Author
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Cervenka I, Al Rahmoun M, Mahamat-Saleh Y, Fournier A, Boutron-Ruault MC, Severi G, Caini S, Palli D, Ghiasvand R, Veierod MB, Botteri E, Tjønneland A, Olsen A, Fortner RT, Kaaks R, Schulze MB, Panico S, Trichopoulou A, Dessinioti C, Niforou K, Sieri S, Tumino R, Sacerdote C, Bueno-de-Mesquita B, Sandanger TM, Colorado-Yohar S, Sánchez MJ, Gil Majuelo L, Lujan-Barroso L, Ardanaz E, Merino S, Isaksson K, Butt S, Ljuslinder I, Jansson M, Travis RC, Khaw KT, Weiderpass E, Dossus L, Rinaldi S, and Kvaskoff M
- Subjects
- Adult, Aged, Confounding Factors, Epidemiologic, Estrogen Replacement Therapy statistics & numerical data, Europe epidemiology, Female, Humans, Incidence, Melanoma etiology, Middle Aged, Postmenopause, Premenopause, Proportional Hazards Models, Prospective Studies, Risk Factors, Skin Neoplasms etiology, Surveys and Questionnaires statistics & numerical data, Time Factors, Contraceptives, Oral, Hormonal adverse effects, Estrogen Replacement Therapy adverse effects, Melanoma epidemiology, Skin Neoplasms epidemiology
- Abstract
Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (p
homogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations., (© 2019 UICC.)- Published
- 2020
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36. LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer.
- Author
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Faraz M, Tellström A, Ardnor CE, Grankvist K, Huminiecki L, Tavelin B, Henriksson R, Hedman H, and Ljuslinder I
- Subjects
- Breast Neoplasms genetics, Breast Neoplasms surgery, Case-Control Studies, Female, Follow-Up Studies, Humans, In Situ Hybridization, Fluorescence, Middle Aged, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local surgery, Prognosis, Survival Rate, Biomarkers, Tumor genetics, Breast Neoplasms pathology, Gene Dosage, Membrane Glycoproteins genetics, Neoplasm Recurrence, Local pathology, Polymerase Chain Reaction methods, Receptor, ErbB-2 genetics
- Abstract
Background: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer., Methods: We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols., Results: Four of the LRIG1/reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/- 0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases., Conclusions: Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
- Published
- 2020
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37. Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells.
- Author
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Li X, Larsson P, Ljuslinder I, Öhlund D, Myte R, Löfgren-Burström A, Zingmark C, Ling A, Edin S, and Palmqvist R
- Abstract
Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF -mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF -mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.
- Published
- 2020
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38. PET/MRI and PET/CT hybrid imaging of rectal cancer - description and initial observations from the RECTOPET (REctal Cancer trial on PET/MRI/CT) study.
- Author
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Rutegård MK, Båtsman M, Axelsson J, Brynolfsson P, Brännström F, Rutegård J, Ljuslinder I, Blomqvist L, Palmqvist R, Rutegård M, and Riklund K
- Subjects
- Adenocarcinoma pathology, Adult, Aged, Female, Fluorodeoxyglucose F18, Humans, Male, Middle Aged, Neoplasm Staging, Radiopharmaceuticals, Rectal Neoplasms pathology, Adenocarcinoma diagnostic imaging, Magnetic Resonance Imaging, Multimodal Imaging, Positron Emission Tomography Computed Tomography, Rectal Neoplasms diagnostic imaging
- Abstract
Purpose: The role of hybrid imaging using
18 F-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET), computed tomography (CT) and magnetic resonance imaging (MRI) to improve preoperative evaluation of rectal cancer is largely unknown. To investigate this, the RECTOPET (REctal Cancer Trial on PET/MRI/CT) study has been launched with the aim to assess staging and restaging of primary rectal cancer. This report presents the study workflow and the initial experiences of the impact of PET/CT on staging and management of the first patients included in the RECTOPET study., Methods: This prospective cohort study, initiated in September 2016, is actively recruiting patients from Region Västerbotten in Sweden. This pilot study includes patients recruited and followed up until December 2017. All patients had a biopsy-verified rectal adenocarcinoma and underwent a minimum of one preoperative FDG-PET/CT and FDG-PET/MRI examination. These patients were referred to the colorectal cancer multidisciplinary team meeting at Umeå University Hospital. All available data were evaluated when making management recommendations. The clinical course was noted and changes consequent to PET imaging were described; surgical specimens underwent dedicated MRI for anatomical matching between imaging and histopathology., Results: Twenty-four patients have so far been included in the study. Four patients were deemed unresectable, while 19 patients underwent or were scheduled for surgery; one patient was enrolled in a watch-and-wait programme after restaging. Consequent to taking part in the study, two patients were upstaged to M1 disease: one patient was diagnosed with a solitary hepatic metastasis detected using PET/CT and underwent metastasectomy prior to rectal cancer surgery, while one patient with a small, but metabolically active, lung nodulus experienced no change of management. PET/MRI did not contribute to any recorded change in patient management., Conclusions: The RECTOPET study investigating the role of PET/CT and PET/MRI for preoperative staging of primary rectal cancer patients will provide novel data that clarify the value of adding hybrid to conventional imaging, and the role of PET/CT versus PET/MRI., Trial Registration: NCT03846882 .- Published
- 2019
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39. Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.
- Author
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Jespersen H, Olofsson Bagge R, Ullenhag G, Carneiro A, Helgadottir H, Ljuslinder I, Levin M, All-Eriksson C, Andersson B, Stierner U, Nilsson LM, Nilsson JA, and Ny L
- Subjects
- Administration, Intravenous, Administration, Oral, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzamides therapeutic use, Drug Administration Schedule, Female, Humans, Male, Prospective Studies, Pyridines therapeutic use, Research Design, Treatment Outcome, Antibodies, Monoclonal, Humanized administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Benzamides administration & dosage, Melanoma drug therapy, Pyridines administration & dosage, Uveal Neoplasms drug therapy
- Abstract
Background: While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells., Methods: The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200 mg intravenously every third week in combination with entinostat 5 mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24 months., Discussion: The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM., Trial Registration: ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
- Published
- 2019
- Full Text
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40. Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition.
- Author
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Bradbury KE, Appleby PN, Tipper SJ, Travis RC, Allen NE, Kvaskoff M, Overvad K, Tjønneland A, Halkjaer J, Cervenka I, Mahamat-Saleh Y, Bonnet F, Kaaks R, Fortner RT, Boeing H, Trichopoulou A, La Vecchia C, Stratigos AJ, Palli D, Grioni S, Matullo G, Panico S, Tumino R, Peeters PH, Bueno-de-Mesquita HB, Ghiasvand R, Veierød MB, Weiderpass E, Bonet C, Molina E, Huerta JM, Larrañaga N, Barricarte A, Merino S, Isaksson K, Stocks T, Ljuslinder I, Hemmingsson O, Wareham N, Khaw KT, Gunter MJ, Rinaldi S, Tsilidis KK, Aune D, Riboli E, and Key TJ
- Subjects
- Adult, Aged, Breast Neoplasms etiology, Breast Neoplasms metabolism, Case-Control Studies, Europe, Female, Humans, Male, Middle Aged, Odds Ratio, Prospective Studies, Prostatic Neoplasms etiology, Risk Factors, Insulin-Like Growth Factor I metabolism, Melanoma etiology, Melanoma metabolism, Nutritional Status physiology
- Abstract
Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2019
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41. The BRCA1 exon 13 duplication: clinical characteristics of 22 families in Northern Sweden.
- Author
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Edwinsdotter Ardnor C, Rosén A, Ljuslinder I, and Melin B
- Subjects
- Adult, Age of Onset, Aged, Aged, 80 and over, Breast Neoplasms diagnosis, Colonic Neoplasms diagnosis, Exons genetics, Female, Gene Rearrangement genetics, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Testing statistics & numerical data, Germ-Line Mutation, Humans, Male, Medical History Taking statistics & numerical data, Middle Aged, Ovarian Neoplasms diagnosis, Prostatic Neoplasms diagnosis, Risk Assessment, Sweden, BRCA1 Protein genetics, Breast Neoplasms genetics, Colonic Neoplasms genetics, Ovarian Neoplasms genetics, Prostatic Neoplasms genetics
- Abstract
The clinical management of BRCA1/2 mutation carriers requires accurate cancer risk estimates. Cancer risks vary according to type and location of the mutation and since there is limited information about mutation-specific cancer risks, genotype-phenotype correlation studies are needed. This is a report of 22 families with the same mutation, BRCA1 duplication exon 13, a mutation that is found world-wide, with the objective to describe the cancer history found in these families. We studied 69 confirmed carriers, 53 women and 16 men, and additionally 29 women who were clinically expected carriers. Among the confirmed carriers, 27 women (51%) were diagnosed with breast cancer, 10 (19%) with ovarian cancer, 5 (9%) with breast and ovarian cancer and 17 (32%) without cancer. Nine women (17%) with breast cancer were 35 years or younger at diagnose. Also, two cases of early onset colon cancer were found, and 37,5% of the male carriers were diagnosed with prostate cancer. These data may have implications for risk assessment and cancer prevention decision making for carriers of the BRCA1 duplication exon 13 mutation.
- Published
- 2019
- Full Text
- View/download PDF
42. Plasma miRNA can detect colorectal cancer, but how early?
- Author
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Wikberg ML, Myte R, Palmqvist R, van Guelpen B, and Ljuslinder I
- Subjects
- Adult, Aged, Aged, 80 and over, Area Under Curve, Biomarkers, Tumor blood, Case-Control Studies, Colorectal Neoplasms blood, Colorectal Neoplasms genetics, Early Detection of Cancer, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Prognosis, Real-Time Polymerase Chain Reaction, Up-Regulation, Biomarkers, Tumor genetics, Colorectal Neoplasms diagnosis, Gene Expression Profiling methods, MicroRNAs blood
- Abstract
Colorectal cancer (CRC) is a major cause of deaths worldwide but has a good prognosis if detected early. The need for efficient, preferable non- or minimally invasive, inexpensive screening tools is therefore critical. We analyzed 12 miRNAs in pre- and postdiagnostic plasma samples to evaluate their potential as CRC screening markers. We used a unique study design with two overlapping cohorts, allowing analysis of pre- and postdiagnostic samples from 58 patients with CRC and matched healthy controls. Plasma concentrations of miR-15b, -16, -18a, -19a, 21, -22, -25, -26a, -29c, -142-5p, -150, and -192 were measured by semi-quantitative real-time PCR. Concentrations of miR-18a, -21, -22, and -25 in plasma from patients with CRC were significantly altered compared to healthy controls. Combined as a multimarker panel, they detected CRC with an AUC of 0.93. Furthermore, levels of these three miRNAs also showed different levels in the prediagnostic case samples close to diagnosis. Only miR-21-levels were elevated several years before diagnosis. Plasma levels of miR-18a, -21, -22, and -25 show promise as screening biomarkers for CRC. However, based on our unique analysis of prediagnostic and postdiagnostic samples from the same patients, we conclude that circulating miRNAs elevated at diagnosis may not automatically be suitable for CRC screening, if the increase occurs too close to clinical diagnosis., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2018
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43. U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- Author
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Glimelius B, Melin B, Enblad G, Alafuzoff I, Beskow A, Ahlström H, Bill-Axelson A, Birgisson H, Björ O, Edqvist PH, Hansson T, Helleday T, Hellman P, Henriksson K, Hesselager G, Hultdin M, Häggman M, Höglund M, Jonsson H, Larsson C, Lindman H, Ljuslinder I, Mindus S, Nygren P, Pontén F, Riklund K, Rosenquist R, Sandin F, Schwenk JM, Stenling R, Stålberg K, Stålberg P, Sundström C, Thellenberg Karlsson C, Westermark B, Bergh A, Claesson-Welsh L, Palmqvist R, and Sjöblom T
- Subjects
- Humans, Sweden, Biological Specimen Banks organization & administration, Biomarkers, Tumor, Neoplasms
- Abstract
Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population., Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data., Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort., Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
- Published
- 2018
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44. MicroRNA Expression in KRAS - and BRAF -mutated Colorectal Cancers.
- Author
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Lundberg IV, Wikberg ML, Ljuslinder I, Li X, Myte R, Zingmark C, Löfgren-Burström A, Edin S, and Palmqvist R
- Subjects
- Caco-2 Cells, Gene Expression Regulation, Neoplastic, Humans, Colorectal Neoplasms genetics, MicroRNAs genetics, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Background/aim: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS- and BRAF-mutated CRCs., Materials and Methods: Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF., Results: Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors., Conclusion: Our results suggest that KRAS- and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS- and BRAF-mutated tumors was evident for the miRNAs analyzed in this study., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
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- 2018
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45. Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition.
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Caini S, Masala G, Saieva C, Kvaskoff M, Savoye I, Sacerdote C, Hemmingsson O, Hammer Bech B, Overvad K, Tjønneland A, Petersen KE, Mancini FR, Boutron-Ruault MC, Cervenka I, Kaaks R, Kühn T, Boeing H, Floegel A, Trichopoulou A, Valanou E, Kritikou M, Tagliabue G, Panico S, Tumino R, Bueno-de-Mesquita HB, Peeters PH, Veierød MB, Ghiasvand R, Lukic M, Quirós JR, Chirlaque MD, Ardanaz E, Salamanca Fernández E, Larrañaga N, Zamora-Ros R, Maria Nilsson L, Ljuslinder I, Jirström K, Sonestedt E, Key TJ, Wareham N, Khaw KT, Gunter M, Huybrechts I, Murphy N, Tsilidis KK, Weiderpass E, and Palli D
- Subjects
- Adult, Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Prospective Studies, Registries, Risk Assessment, Risk Factors, Surveys and Questionnaires, Anticarcinogenic Agents, Coffee, Neoplasms epidemiology, Neoplasms prevention & control, Tea
- Abstract
In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma., (© 2017 UICC.)
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- 2017
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46. Cellular immune activity biomarker neopterin is associated hyperlipidemia: results from a large population-based study.
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Chuang SC, Boeing H, Vollset SE, Midttun Ø, Ueland PM, Bueno-de-Mesquita B, Lajous M, Fagherazzi G, Boutron-Ruault MC, Kaaks R, Küehn T, Pischon T, Drogan D, Tjønneland A, Overvad K, Quirós JR, Agudo A, Molina-Montes E, Dorronsoro M, Huerta JM, Barricarte A, Khaw KT, Wareham NJ, Travis RC, Trichopoulou A, Lagiou P, Trichopoulos D, Masala G, Agnoli C, Tumino R, Mattiello A, Peeters PH, Weiderpass E, Palmqvist R, Ljuslinder I, Gunter M, Lu Y, Cross AJ, Riboli E, Vineis P, and Aleksandrova K
- Abstract
Background: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Results: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p < 0.01 for men and 9.2 %, p < 0.01 for women), whereas no association was observed with the rest of the MetS components as well as with MetS overall (per 10 nmol/L: OR = 1.42, 95 % CI = 0.85-2.39 for men and OR = 1.38, 95 % CI = 0.79-2.43)., Conclusions: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.
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- 2016
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47. Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer.
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Nimptsch K, Aleksandrova K, Boeing H, Janke J, Lee YA, Jenab M, Kong SY, Tsilidis KK, Weiderpass E, Bueno-De-Mesquita HB, Siersema PD, Jansen EH, Trichopoulou A, Tjønneland A, Olsen A, Wu C, Overvad K, Boutron-Ruault MC, Racine A, Freisling H, Katzke V, Kaaks R, Lagiou P, Trichopoulos D, Severi G, Naccarati A, Mattiello A, Palli D, Grioni S, Tumino R, Peeters PH, Ljuslinder I, Nyström H, Brändstedt J, Sánchez MJ, Gurrea AB, Bonet CB, Chirlaque MD, Dorronsoro M, Quirós JR, Travis RC, Khaw KT, Wareham N, Riboli E, Gunter MJ, and Pischon T
- Subjects
- Aged, Case-Control Studies, Colorectal Neoplasms epidemiology, Colorectal Neoplasms pathology, Female, Humans, Male, Middle Aged, Risk Factors, alpha-2-HS-Glycoprotein genetics, Colorectal Neoplasms blood, Colorectal Neoplasms genetics, alpha-2-HS-Glycoprotein metabolism
- Abstract
Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 µg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 µg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development., (© 2015 UICC.)
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- 2015
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48. Erratum to: Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial): study protocol for a randomized controlled trial.
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Olofsson Bagge R, Ny L, All-Ericsson C, Sternby Eilard M, Rizell M, Cahlin C, Stierner U, Lönn U, Hansson J, Ljuslinder I, Lundgren L, Ullenhag G, Kiilgaard JF, Nilsson J, and Lindnér P
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- 2015
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49. Human papillomavirus antibodies and future risk of anogenital cancer: a nested case-control study in the European prospective investigation into cancer and nutrition study.
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Kreimer AR, Brennan P, Lang Kuhs KA, Waterboer T, Clifford G, Franceschi S, Michel A, Willhauck-Fleckenstein M, Riboli E, Castellsagué X, Hildesheim A, Fortner RT, Kaaks R, Palli D, Ljuslinder I, Panico S, Clavel-Chapelon F, Boutron-Ruault MC, Mesrine S, Trichopoulou A, Lagiou P, Trichopoulos D, Peeters PH, Cross AJ, Bueno-de-Mesquita HB, Vineis P, Larrañaga N, Pala V, Sánchez MJ, Navarro C, Barricarte A, Tumino R, Khaw KT, Wareham N, Boeing H, Steffen A, Travis RC, Quirós JR, Weiderpass E, Pawlita M, and Johansson M
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- Adult, Aged, Anus Neoplasms virology, Biomarkers, Tumor, Case-Control Studies, Europe, Female, Follow-Up Studies, Genital Neoplasms, Female virology, Genital Neoplasms, Male virology, Genotype, Humans, Male, Middle Aged, Nutritional Sciences, Oncogene Proteins, Viral immunology, Papillomaviridae, Papillomavirus Infections complications, Prospective Studies, Repressor Proteins immunology, Treatment Outcome, Antibodies, Viral blood, Anus Neoplasms immunology, Genital Neoplasms, Female immunology, Genital Neoplasms, Male immunology, Papillomavirus Infections immunology
- Abstract
Purpose: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort., Methods: Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression., Results: HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis., Conclusion: HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers., (© 2015 by American Society of Clinical Oncology.)
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- 2015
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50. Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.
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Hughes DJ, Fedirko V, Jenab M, Schomburg L, Méplan C, Freisling H, Bueno-de-Mesquita HB, Hybsier S, Becker NP, Czuban M, Tjønneland A, Outzen M, Boutron-Ruault MC, Racine A, Bastide N, Kühn T, Kaaks R, Trichopoulos D, Trichopoulou A, Lagiou P, Panico S, Peeters PH, Weiderpass E, Skeie G, Dagrun E, Chirlaque MD, Sánchez MJ, Ardanaz E, Ljuslinder I, Wennberg M, Bradbury KE, Vineis P, Naccarati A, Palli D, Boeing H, Overvad K, Dorronsoro M, Jakszyn P, Cross AJ, Quirós JR, Stepien M, Kong SY, Duarte-Salles T, Riboli E, and Hesketh JE
- Subjects
- Adult, Aged, Case-Control Studies, Colorectal Neoplasms blood, Colorectal Neoplasms epidemiology, Europe epidemiology, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nutritional Status, Prognosis, Prospective Studies, ROC Curve, Risk Factors, Spectrometry, X-Ray Emission, Biomarkers, Tumor blood, Colorectal Neoplasms etiology, Selenium blood, Selenoprotein P blood
- Abstract
Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 μg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (p(trend) = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (p(trend) = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (p(trend) = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (p(trend) = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women., (© 2014 UICC.)
- Published
- 2015
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