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  • 1.
    Andersson, Anne
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Enblad, Gunilla
    Tavelin, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Björkholm, Magnus
    Linderoth, Johan
    Lagerlöf, I
    Merup, Mats
    Sender, Mark
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma2008Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 98, nr 5, s. 1001-1005Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ≥2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme.

  • 2. Bamia, C.
    et al.
    Lagiou, P.
    Jenab, M.
    Aleksandrova, K.
    Fedirko, V.
    Trichopoulos, D.
    Overvad, K.
    Tjonneland, A.
    Olsen, A.
    Clavel-Chapelon, F.
    Boutron-Ruault, M-C
    Kvaskoff, M.
    Katzke, V. A.
    Kuehn, T.
    Boeing, H.
    Noethlings, U.
    Palli, D.
    Sieri, S.
    Panico, S.
    Tumino, R.
    Naccarati, A.
    Bueno-de-Mesquita, H. B(As)
    Peeters, P. H. M.
    Weiderpass, E.
    Skeie, G.
    Quiros, J. R.
    Agudo, A.
    Chirlaque, M-D
    Sanchez, M-J
    Ardanaz, E.
    Dorronsoro, M.
    Ericson, U.
    Nilsson, Lena Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Arktiskt centrum vid Umeå universitet (Arcum).
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Khaw, K-T
    Wareham, N.
    Key, T. J.
    Travis, R. C.
    Ferrari, P.
    Stepien, M.
    Duarte-Salles, T.
    Norat, T.
    Murphy, N.
    Riboli, E.
    Trichopoulou, A.
    Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study2015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, nr 7, s. 1273-1282Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. Methods: In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. Results: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. Conclusions: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.

  • 3.
    Bergh, Johanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Marklund, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Gustavsson, C
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wiklund, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grönberg, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Allard, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Alexeyev, Olog
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    No link between viral findings in the prostate and subsequent cancer development2007Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 96, nr 1, s. 137-139Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.

  • 4. Besevic, Jelena
    et al.
    Gunter, Marc J.
    Fortner, Renee T.
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Onland-Moret, N. Charlotte
    Dossus, Laure
    Tjonneland, Anne
    Hansen, Louise
    Overvad, Kim
    Mesrine, Sylvie
    Baglietto, Laura
    Clavel-Chapelon, Francoise
    Kaaks, Rudolf
    Aleksandrova, Krasimira
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Masala, Giovanna
    Agnoli, Claudia
    Tumino, Rosario
    Ricceri, Fulvio
    Panico, Salvatore
    Bueno-de-Mesquita, H. B. (as)
    Peeters, Petra H.
    Jareid, Mie
    Ramon Quiros, J.
    Duell, Eric J.
    Sanchez, Maria-Jose
    Larranaga, Nerea
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Dias, Joana A.
    Sonestedt, Emily
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wareham, Nicholas J.
    Khaw, Kay-Tee
    Travis, Ruth C.
    Rinaldi, Sabina
    Romieu, Isabelle
    Riboli, Elio
    Merritt, Melissa A.
    Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study2015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 113, nr 11, s. 1622-1631Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (>= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.

  • 5.
    Boldrup, Linda
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Coates, P J
    Laurell, G
    Wilms, Torben
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Fahraeus, R
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Downregulation of miRNA-424: a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma2015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, nr 11, s. 1760-1765Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The overall survival for patients with squamous cell carcinoma of the tongue is low and the search for early diagnostic and prognostic markers is thus essential. MicroRNAs have been suggested as potential prognostic and diagnostic candidates in squamous cell carcinoma of head and neck in general. Methods: On the basis of the known differences between sub-sites within the oral cavity, we investigated the expression and role of microRNA-424 in squamous cell carcinoma arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and plasma samples. Results: Levels of microRNA-424 were upregulated in tongue squamous cell carcinoma, but not in tumours originating from gingiva or floor of the mouth. Interestingly, microRNA-424 was downregulated in clinically normal tongue tissue next to tumour compared with completely healthy tongue, indicating that microRNA-424 could be a marker of field cancerisation in this tumour type. However, expression of microRNA-424 in a tongue-derived epithelial cell line revealed no significant changes in the expression profile of proteins and genes. Conclusions: Our patient data show that microRNA-424 alterations are a marker of field cancerisation specific for tongue tumourigenesis, which also could have a role in development of tongue squamous cell carcinoma.

  • 6. Claassen, Yvette H. M.
    et al.
    Vermeer, Nina C. A.
    Iversen, Lene H.
    van Eycken, Elizabeth
    Guren, Marianne G.
    Mroczkowski, Pawel
    Martling, Anna
    Codina Cazador, Antonio
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Vandendael, Tamara
    Wibe, Arne
    Møller, Bjørn
    Lippert, Hans
    Rutten, Harm J. T.
    Portielje, Johanneke E. A.
    Liefers, Gerrit J.
    Holman, Fabian A.
    van de Velde, Cornelis J. H.
    Bastiaannet, Esther
    Treatment and survival of rectal cancer patients over the age of 80 years: a EURECCA international comparison2018Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 119, nr 4, s. 517-522Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+.

    METHODS: Patients of >= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients.

    RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO.

    CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.

  • 7. Couto, E
    et al.
    Boffetta, P
    Lagiou, P
    Ferrari, P
    Buckland, G
    Overvad, K
    Dahm, C C
    Tjønneland, A
    Olsen, A
    Clavel-Chapelon, F
    Boutron-Ruault, M-C
    Cottet, V
    Trichopoulos, D
    Naska, A
    Benetou, V
    Kaaks, R
    Rohrmann, S
    Boeing, H
    von Ruesten, A
    Panico, S
    Pala, V
    Vineis, P
    Palli, D
    Tumino, R
    May, A
    Peeters, P H
    Bueno-de-Mesquita, H B
    Büchner, F L
    Lund, E
    Skeie, G
    Engeset, D
    Gonzalez, C A
    Navarro, C
    Rodríguez, L
    Sánchez, M-J
    Amiano, P
    Barricarte, A
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Manjer, J
    Wirfärt, E
    Allen, N E
    Crowe, F
    Khaw, K-T
    Wareham, N
    Moskal, A
    Slimani, N
    Jenab, M
    Romaguera, D
    Mouw, T
    Norat, T
    Riboli, E
    Trichopoulou, A
    Mediterranean dietary pattern and cancer risk in the EPIC cohort.2011Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, nr 9, s. 1493-1499Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.

    METHODS: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142,605 men and 335,873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.

    RESULTS: In all, 9669 incident cancers in men and 21,062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.

    CONCLUSION: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.

  • 8. Disney-Hogg, Linden
    et al.
    Sud, Amit
    Law, Philip J.
    Cornish, Alex J.
    Kinnersley, Ben
    Ostrom, Quinn T.
    Labreche, Karim
    Eckel-Passow, Jeanette E.
    Armstrong, Georgina N.
    Claus, Elizabeth B.
    Il'yasova, Dora
    Schildkraut, Joellen
    Barnholtz-Sloan, Jill S.
    Olson, Sara H.
    Bernstein, Jonine L.
    Lai, Rose K.
    Swerdlow, Anthony J.
    Simon, Matthias
    Hoffmann, Per
    Nöthen, Markus M.
    Jöckel, Karl-Heinz
    Chanock, Stephen
    Rajaraman, Preetha
    Johansen, Christoffer
    Jenkins, Robert B.
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wrensch, Margaret R.
    Sanson, Marc
    Bondy, Melissa L.
    Houlston, Richard S.
    Influence of obesity-related risk factors in the aetiology of glioma2018Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, nr 7, s. 1020-1027Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Obesity and related factors have been implicated as possible aetiological factors for the development of glioma in epidemiological observation studies. We used genetic markers in a Mendelian randomisation framework to examine whether obesity-related traits influence glioma risk. This methodology reduces bias from confounding and is not affected by reverse causation. METHODS: Genetic instruments were identified for 10 key obesity-related risk factors, and their association with glioma risk was evaluated using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. The estimated odds ratio of glioma associated with each of the genetically defined obesity-related traits was used to infer evidence for a causal relationship. RESULTS: No convincing association with glioma risk was seen for genetic instruments for body mass index, waist-to-hip ratio, lipids, type-2 diabetes, hyperglycaemia or insulin resistance. Similarly, we found no evidence to support a relationship between obesity-related traits with subtypes of glioma-glioblastoma (GBM) or non-GBM tumours. CONCLUSIONS: This study provides no evidence to implicate obesity-related factors as causes of glioma.

  • 9. Duffy, SW
    et al.
    Lynge, E
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Reply: estimation of lead-time and overdiagnosis in breast cancer screening2009Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, nr 1, s. 220-220Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Eklöf, Vincy
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikberg, Maria L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Edin, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Dahlin, Anna M.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jonsson, Björn-Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Öberg, Å.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Rutegård, Jörgen
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer2013Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, nr 10, s. 2153-2163Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC. Patients We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n = 197) and Colorectal Cancer in Umea Study (CRUMS; n = 414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression. Results Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P = 0.003 and CRUMS; P = 0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information. Conclusions Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.

  • 11. Fortner, Renée T.
    et al.
    Schock, Helena
    Jung, Seungyoun
    Allen, Naomi E.
    Arslan, Alan A.
    Brinton, Louise A.
    Egleston, Brian L.
    Falk, Roni T.
    Gunter, Marc J.
    Helzlsouer, Kathy J.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johnson, Theron S.
    Kaaks, Rudolf
    Krogh, Vittorio
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Merritt, Melissa A.
    Navarro, Carmen
    Onland-Moret, N. Charlotte
    Palli, Domenico
    Shu, Xiao-Ou
    Sluss, Patrick M.
    Staats, Paul N.
    Trichopoulou, Antonia
    Weiderpass, Elisabete
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Dorgan, Joanne F.
    Anti-Mullerian hormone and endometrial cancer: a multi-cohort study2017Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 117, nr 9, s. 1412-1418Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. Methods: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. AntiMullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Results: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog(2): 1.07 (0.99-1.17)), or with any of the examined subgroups. Conclusions: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.

  • 12. Grote, VA
    et al.
    Kaaks, R
    Nieters, A
    Tjonneland, A
    Halkjaer, J
    Overvad, K
    Nielsen, MR Skjelbo
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Racine, A
    Teucher, B
    Becker, S
    Pischon, T
    Boeing, H
    Trichopoulou, A
    Cassapa, C
    Stratigakou, V
    Palli, D
    Krogh, V
    Tumino, R
    Vineis, P
    Panico, S
    Rodriguez, L
    Duell, EJ
    Sanchez, M-J
    Dorronsoro, M
    Navarro, C
    Gurrea, AB
    Siersema, PD
    Peeters, PHM
    Ye, W
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lindkvist, B
    Johansen, D
    Khaw, K-T
    Wareham, N
    Allen, NE
    Travis, RC
    Fedirko, V
    Jenab, M
    Michaud, DS
    Chuang, S-C
    Romaguera, D
    Bueno-de-Mesquita, HB
    Rohrmann, S
    Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, nr 11, s. 1866-1874Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce.

    METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-a (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models.

    RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR = 1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR = 1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI.

    CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer. British Journal of Cancer (2012) 106, 1866-1874. doi:10.1038/bjc.2012.172 www.bjcancer.com Published online 26 April 2012 (C) 2012 Cancer Research UK

  • 13.
    Harlid, Sophia
    et al.
    Lund University, Department of Laboratory Sciences.
    Ivarsson, Malin I. L.
    Butt, Salma
    Grzybowska, Eva
    Eyfjord, Jorunn E.
    Lenner, Per
    Forsti, Asta
    Hemminki, Kari
    Manjer, Jonas
    Dillner, Joakim
    Carlson, Joyce
    Combined effect of low-penetrant SNPs on breast cancer risk2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, nr 2, s. 389-396Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status.

    METHODS: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression.

    RESULTS: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 x 10(-20) and 1.5 x 10(-25), respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59-2.14; 10 SNPs) and 2.12 (95% CI: 1.80-2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 x 10(-4)).

    CONCLUSION: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer. British Journal of Cancer (2012) 106, 389-396. doi:10.1038/bjc.2011.461 www.bjcancer.com Published online 1 November 2011 (C) 2012 Cancer Research UK

  • 14. Hartana, Ciputra Adijaya
    et al.
    Kinn, Johan
    Rosenblatt, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Anania, Stefan
    Alamdari, Farhood
    Glise, Hans
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Winqvist, Ola
    Detection of micrometastases by flow cytometry in sentinel lymph nodes from patients with renal tumours2016Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 115, nr 8, s. 957-966Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Stage is an important prognostic factor in renal tumours and dissemination to regional lymph nodes is associated with poor outcomes. Lymph nodes are routinely assessed by immunohistochemistry and microscopic evaluation, a time-consuming process where micrometastases might go undiagnosed. We evaluate an alternative method for detecting metastatic cells in sentinel nodes (SNs) by flow cytometry.

    METHODS: A total of 15 nodes from 5 patients diagnosed with renal tumours were analysed by flow cytometry. Staining for the intracellular marker cytokeratin 18 (CK18) with the surface markers carbonic anhydrase IX (CA9) and Cadherin 6 were used in flow cytometry analysis. Peripheral blood mononuclear cells (PBMCs) with the addition of known concentrations of cancer cell lines were analysed to investigate the sensitivity of micrometastasis detection.

    RESULTS: Stability of the assay was marked by low intra-assay variability (coefficient of variance ⩽16%) and low inter-assay variability (R(2)=0.9996-1). Eight nodes in four patients were positive for metastasis; six of them were considered being micrometastatic. These metastases were undetected by routine pathology and the patients were restaged from pN0 to pN1.

    CONCLUSIONS: Flow cytometry is able to detect micrometastases in lymph nodes of renal tumour patients that were undetected under H&E examination.

  • 15. Heikkila, Katriina
    et al.
    Nyberg, Solja T.
    Madsen, Ida E. H.
    de Vroome, Ernest
    Alfredsson, Lars
    Bjorner, Jacob J.
    Borritz, Marianne
    Burr, Hermann
    Erbel, Raimund
    Ferrie, Jane E.
    Fransson, Eleonor I.
    Geuskens, Goedele A.
    Hooftman, Wendela E.
    Houtman, Irene L.
    Jöckel, Karl-Heinz
    Knutsson, Anders
    Koskenvuo, Markku
    Lunau, Thorsten
    Nielsen, Martin L.
    Nordin, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Stress Research Institute, Stockholm University, Stockholm SE-106 91.
    Oksanen, Tuula
    Pejtersen, Jan H.
    Pentti, Jaana
    Shipley, Martin J.
    Steptoe, Andrew
    Suominen, Sakari B.
    Theorell, Töres
    Vahtera, Jussi
    Westerholm, Peter J. M.
    Westerlund, Hugo
    Dragano, Nico
    Rugulies, Reiner
    Kawachi, Ichiro
    Batty, G. David
    Singh-Manoux, Archana
    Virtanen, Marianna
    Kivimäki, Mika
    Long working hours and cancer risk: a multi-cohort study2016Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, nr 7, s. 813-818Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Working longer than the maximum recommended hours is associated with an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer is unclear. Methods: This multi-cohort study examined the association between working hours and cancer risk in 116 462 men and women who were free of cancer at baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers; weekly working hours were self-reported. Results: During median follow-up of 10.8 years, 4371 participants developed cancer (n colorectal cancer: 393; n lung cancer: 247; n breast cancer: 833; and n prostate cancer: 534). We found no clear evidence for an association between working hours and the overall cancer risk. Working hours were also unrelated the risk of incident colorectal, lung or prostate cancers. Working >= 55 h per week was associated with 1.60-fold (95% confidence interval 1.12-2.29) increase in female breast cancer risk independently of age, socioeconomic position, shift-and night-time work and lifestyle factors, but this observation may have been influenced by residual confounding from parity. Conclusions: Our findings suggest that working long hours is unrelated to the overall cancer risk or the risk of lung, colorectal or prostate cancers. The observed association with breast cancer would warrant further research.

  • 16. Hellman, K
    et al.
    Lindquist, David
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Oncology Research Laboratory, Department of Radiation Sciences, Umeå University.
    Ranhem, C
    Wilander, E
    Andersson, S
    Human papillomavirus, p16(INK4A), and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina2014Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 110, nr 6, s. 1561-1570Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:This study aimed to determine human papillomavirus (HPV) status and to investigate p16(INK4A) and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV).Methods:The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (2 years) and long-term (8 years) PCV survivors. p16(INK4A) and Ki-67 expression was evaluated by immunohistochemistry.Results:Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16(INK4A) expression was significantly correlated with low histopathological grade (P=0.004), HPV positivity (P=0.032), and long-term survival (P=0.045). High Ki-67 expression was negatively correlated with histopathological grade (P<0.001) and tumour size (P=0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival.Conclusion:High p16(INK4A) expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16(INK4A) and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16(INK4A) expression as a marker for HPV positivity, but this has to be further elucidated.

  • 17. Holmberg, L.
    et al.
    Wong, Y. N. S.
    Tabar, L.
    Ringberg, A.
    Karlsson, P.
    Arnesson, L-G
    Sandelin, K.
    Anderson, H.
    Garmo, H.
    Emdin, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study2013Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, nr 4, s. 812-819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. Methods: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. Results: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (Cl) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% Cl 2.20-140). Conclusion: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

  • 18. Honkaniemi, E
    et al.
    Talekar, G
    Huang, W
    Bogdanovic, G
    Forestier, E
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    von Doblen, U
    Engvall, M
    Ornelles, D A
    Gooding, L R
    Gustafsson, B
    Adenovirus DNA in Guthrie cards from children who develop acute lymphoblastic leukaemia (ALL).2010Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 102, nr 5, s. 796-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In search of a proposed viral aetiology of childhood acute lymphoblastic leukaemia (ALL), the common species C adenoviruses were analysed in Guthrie cards. METHODS: Guthrie cards from 243 children who later developed ALL and from 486 matched controls were collected and analysed by nested polymerase chain reaction for the presence of adenovirus DNA. RESULTS: Adenovirus DNA was reliably detected from only two subjects, both of whom developed ALL. CONCLUSION: Adenovirus DNA is detected in Guthrie card samples at too low a frequency to reveal an association between adenovirus and the development of leukaemia.

  • 19. Hultdin, M
    et al.
    Rosenquist, R
    Thunberg, U
    Tobin, G
    Norrback, K-F
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Johnson, A
    Sundström, C
    Roos, G
    Association between telomere length and V(H) gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications.2003Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 88, nr 4, s. 593-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The immunoglobulin V(H) gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V(H) genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated V(H) genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and V(H) gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between V(H) gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 6.3 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months). Furthermore, the Ig gene sequence data revealed that samples with high mutations frequency (>6%) had long telomeres ( approximately 8 kbp). Thus, both the telomere and V(H) gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction.

  • 20.
    Hultdin, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rosenquist, R
    Thunberg, U
    Tobin, G
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Johnson, A
    Sundström, C
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Association between telomere length and V-H gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications2003Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 88, nr 4, s. 593-598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The immunoglobulin V-H gene mutation status can divide B-cell chronic lymphocytic leukaemia (CLL) into two entities with a different clinical course. Cases with unmutated V-H genes, considered to evolve from pregerminal centre (GC) cells, have a worse outcome compared to cases showing mutated VH genes, that is, post-GC derived. Also, telomere length has been reported to be of prognostic significance in CLL. Interestingly, telomerase becomes activated during the GC reaction and an elongation of the telomeres occurs in GC B cells. We performed telomere length and VH gene analysis in a series of 61 CLL cases, in order to investigate if the unique telomere lengthening shown in GC B cells could reflect the telomere status in the two subsets of mutated and unmutated CLL. A novel association was found between VH gene mutation status and telomere length, since significantly shorter telomeres were demonstrated in the unmutated group compared to the mutated group (mean length 4.3 vs 63 kbp). Shorter telomeres also constituted a subgroup with a worse prognosis than cases with longer telomeres (median survival 59 vs 159 months), Furthermore, the I-g gene sequence data revealed that samples with high mutations frequency (> 6%) had long telomeres (similar to 8 kbp). Thus, both the telomere and VH gene mutation status in CLL appear linked, which may reflect the proliferative history of the clonal cells with regard to the GC reaction. (C) 2003 Cancer Research UK.

  • 21. Jakubowska, A.
    et al.
    Rozkrut, D.
    Antoniou, A.
    Hamann, U.
    Scott, R. J.
    McGuffog, L.
    Healy, S.
    Sinilnikova, O. M.
    Rennert, G.
    Lejbkowicz, F.
    Flugelman, A.
    Andrulis, I. L.
    Glendon, G.
    Ozcelik, H.
    Thomassen, M.
    Paligo, M.
    Aretini, P.
    Kantala, J.
    Aroer, B.
    Von Wachenfeldt, A.
    Liljegren, A.
    Loman, N.
    Herbst, K.
    Kristoffersson, U.
    Rosenquist, R.
    Karlsson, P.
    Stenmark-Askmalm, M.
    Melin, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Nathanson, K. L.
    Domchek, S. M.
    Byrski, T.
    Huzarski, T.
    Gronwald, J.
    Menkiszak, J.
    Cybulski, C.
    Serrano, P.
    Osorio, A.
    Cajal, T. R.
    Tsitlaidou, M.
    Benitez, J.
    Gilbert, M.
    Rookus, M.
    Aalfs, C. M.
    Kluijt, I.
    Boessenkool-Pape, J. L.
    Meijers-Heijboer, H. E. J.
    Oosterwijk, J. C.
    van Asperen, C. J.
    Blok, M. J.
    Nelen, M. R.
    van den Ouweland, A. M. W.
    Seynaeve, C.
    van der Luijt, R. B.
    Devilee, P.
    Easton, D. F.
    Peock, S.
    Frost, D.
    Platte, R.
    Ellis, S. D.
    Fineberg, E.
    Evans, D. G.
    Lalloo, F.
    Eeles, R.
    Jacobs, C.
    Adlard, J.
    Davidson, R.
    Eccles, D.
    Cole, T.
    Cook, J.
    Godwin, A.
    Bove, B.
    Stoppa-Lyonnet, D.
    Caux-Moncoutier, V.
    Belotti, M.
    Tirapo, C.
    Mazoyer, S.
    Barjhoux, L.
    Boutry-Kryza, N.
    Pujol, P.
    Coupier, I.
    Peyrat, J-P
    Vennin, P.
    Muller, D.
    Fricker, J-P
    Venat-Bouvet, L.
    Johannsson, OTh
    Isaacs, C.
    Schmutzler, R.
    Wappenschmidt, B.
    Meindl, A.
    Arnold, N.
    Varon-Mateeva, R.
    Niederacher, D.
    Sutter, C.
    Deissler, H.
    Preisler-Adams, S.
    Simard, J.
    Soucy, P.
    Durocher, F.
    Chenevix-Trench, G.
    Beesley, J.
    Chen, X.
    Rebbeck, T.
    Couch, F.
    Wang, X.
    Lindor, N.
    Fredericksen, Z.
    Pankratz, V. S.
    Peterlongo, P.
    Bonanni, B.
    Fortuzzi, S.
    Peissel, B.
    Szabo, C.
    Mai, P. L.
    Loud, J. T.
    Lubinski, J.
    Association of PHB 1630 C > T and MTHFR 677 C > T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, nr 12, s. 2016-2024Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. METHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. RESULTS: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95% CI 1.10-2.04 and HR 2.16, 95% CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. CONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.

  • 22. Jenab, M
    et al.
    Riboli, E
    Ferrari, P
    Friesen, M
    Sabate, J
    Norat, T
    Slimani, N
    Tjonneland, A
    Olsen, A
    Overvad, K
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Boeing, H
    Schulz, M
    Linseisen, J
    Nagel, G
    Trichopoulou, A
    Naska, A
    Oikonomou, E
    Berrino, F
    Panico, S
    Palli, D
    Sacerdote, C
    Tumino, R
    Peeters, PH
    Numans, ME
    Bueno-de Mesquita, HB
    Buchner, FL
    Lund, E
    Pera, G
    Chirlaque, MD
    Sanchez, MJ
    Arriola, L
    Barricarte, A
    Quiros, JR
    Johansson, Ingegerd
    Umeå universitet, Medicinsk fakultet, Odontologi, Kariologi.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Berglund, G
    Bingham, S
    Khaw, KT
    Allen, N
    Key, T
    Carneiro, F
    Save, V
    Del Giudice, G
    Plebani, M
    Kaaks, R
    Gonzalez, CA
    Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition2006Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 95, nr 3, s. 406-415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and - and -tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and -tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma -cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30-0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22-0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33-0.93, Ptrend=0.005) and lipid-unadjusted -tocopherol (OR=0.59, 95% CI=0.37-0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted -tocopherol (OR=0.26, 95% CI=0.11-0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and -tocopherol are associated with reduced risk of GC.

  • 23.
    Johansson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersson, Carola
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Moharer, Jasmin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Behnam-Motlagh, Parviz
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Cisplatin-induced expression of Gb3 enables verotoxin-1 treatment of cisplatin resistance in malignant pleural mesothelioma cells2010Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 102, nr 2, s. 383-391Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    A major problem with cisplatin treatment is the development of acquired-drug resistance of the tumour cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the membrane glycolipid globotriasosylceramide (Gb3), a molecule associated with drug resistance. Cisplatin- and VT-1-induced apoptosis involves mitogen-activated protein kinase (MAPK) activation, and deactivation of MAPKs is associated with cisplatin resistance. This study aimed to investigate whether a sub-toxic concentration of VT-1 could enhance cisplatin-induced apoptosis and overcome acquired-cisplatin resistance in cultured cancer cell lines.

    Method:

    P31 and H1299 cells with corresponding cisplatin-resistant sub-lines (P31res/H1299res) were incubated with VT-1 and/or cisplatin followed by determination of Gb3 expression, cell viability, apoptosis, and signalling pathways.

    Results:

    Cells from the resistant sub-lines had elevated Gb3 expression compared with the parental cell lines, and cisplatin further increased Gb3 expression, whereas VT-1 reduced the percentage of Gb3-expressing cells. Combination of cisplatin and sub-toxic concentrations of VT-1 led to a super-additive increase of cytotoxicity and TUNEL staining, especially in the cisplatin-resistant sub-lines. Blockade of Gb3 synthesis by a Gb3 synthesis inhibitor not only led to eradicated TUNEL staining of P31 cells, but also sensitised P31res cells to the induction of apoptosis by cisplatin alone. Cisplatin- and VT-1-induced apoptosis involved the MAPK pathways with increased C-Jun N-terminal kinase and MAPK kinase-3 and -6 phosphorylation.

    Conclusions:

    We show the presence of Gb3 in acquired-cisplatin resistance in P31res and H1299res cells. Cisplatin up-regulated Gb3 expression in all cells and thus sensitised the cells to VT-1-induced cytotoxicity. A strong super-additive effect of combined cisplatin and a sub-toxic concentration of VT-1 in cisplatin-resistant malignant pleural mesothelioma cells were observed, indicating a new potential clinical-treatment approach.

  • 24. Key, T J
    et al.
    Appleby, P N
    Reeves, G K
    Roddam, A W
    Helzlsouer, K J
    Alberg, A J
    Rollison, D E
    Dorgan, J F
    Brinton, L A
    Overvad, K
    Kaaks, R
    Trichopoulou, A
    Clavel-Chapelon, F
    Panico, S
    Duell, E J
    Peeters, P H M
    Rinaldi, S
    Fentiman, I S
    Dowsett, M
    Manjer, J
    Lenner, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Baglietto, L
    English, D R
    Giles, G G
    Hopper, J L
    Severi, G
    Morris, H A
    Hankinson, S E
    Tworoger, S S
    Koenig, K
    Zeleniuch-Jacquotte, A
    Arslan, A A
    Toniolo, P
    Shore, R E
    Krogh, V
    Micheli, A
    Berrino, F
    Barrett-Connor, E
    Laughlin, G A
    Kabuto, M
    Akiba, S
    Stevens, R G
    Neriishi, K
    Land, C E
    Cauley, J A
    Lui, Li Yung
    Cummings, Steven R
    Gunter, M J
    Rohan, T E
    Strickler, H D
    Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies.2011Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, nr 5, s. 709-722Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.

    METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.

    RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.

    CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.

  • 25. Kjellberg, L
    et al.
    Hallmans, G
    Ahren, A M
    Johansson, R
    Bergman, F
    Wadell, G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Angström, T
    Dillner, J
    Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection.2000Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 82, nr 7, s. 1332-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case-control study in the Vasterbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2-3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P < 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2-3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2-3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7-4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3-4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9-4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia.

  • 26. Li, K.
    et al.
    Huesing, A.
    Fortner, R. T.
    Tjonneland, A.
    Hansen, L.
    Dossus, L.
    Chang-Claude, J.
    Bergmann, M.
    Steffen, A.
    Bamia, C.
    Trichopoulos, D.
    Trichopoulou, A.
    Palli, D.
    Mattiello, A.
    Agnoli, C.
    Tumino, R.
    Onland-Moret, N. C.
    Peeters, P. H.
    Bueno-de-Mesquita, H. B(as)
    Gram, I. T.
    Weiderpass, E.
    Sanchez-Cantalejo, E.
    Chirlaque, M-D
    Duell, E. J.
    Ardanaz, E.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, E.
    Khaw, K-T
    Travis, R. C.
    Merritt, M. A.
    Gunter, M. J.
    Riboli, E.
    Ferrari, P.
    Terry, K.
    Cramer, D.
    Kaaks, R.
    An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study2015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, nr 7, s. 1257-1265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. Results: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. Conclusion: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.

  • 27.
    Lindmark, Fredrik
    et al.
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Zheng, S L
    Wiklund, Fredrik
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    A Bälter, K
    Sun, J
    Chang, B
    Hedelin, M
    Clark, J
    Johansson, J-E
    Meyers, D A
    Adami, H-O
    Isaacs, W
    Grönberg, Henrik
    Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi.
    Xu, J
    Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk2005Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 93, nr 4, s. 493-497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1alpha and IL1beta. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the 'ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR = 1.0, 95% CI = 0.8-1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI = 1.3-2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.

  • 28.
    Lindquist, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Näsman, A.
    Department of Oncology-Pathology, Karolinska Institute, SE-171 76, Stockholm, Sweden.
    Tarján, M.
    Department of Pathology and Clinical Cytology, Central Hospital Falun, SE-791 29, Falun, Sweden.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Tot, T.
    Department of Pathology and Clinical Cytology, Central Hospital Falun, SE-791 29, Falun, Sweden.
    Dalianis, T.
    Department of Oncology-Pathology, Karolinska Institute, SE-171 76, Stockholm, Sweden.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Expression of LRIG1 is associated with good prognosis and human papillomavirus status in oropharyngeal cancer2014Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 110, nr 7, s. 1793-1800Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer has increased rapidly during the past decades. HPV is typically associated with a favourable outcome; however, a need exists for new and more effective prognostic and predictive markers for this disease. Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is a tumour suppressor protein that belongs to the LRIG family. LRIG1 expression has prognostic significance in various human cancers, including cervical cancer, where HPV is a key aetiological agent.Methods:The prognostic value of LRIG1 and LRIG2 immunoreactivity was investigated in tumour specimens from a Swedish cohort of patients with tonsillar and base of tongue oropharyngeal cancers, including 278 patients.Results:LRIG1 immunoreactivity correlated with disease-free survival and overall survival in univariate and multivariate analyses. Notably, patients with HPV-positive tumours with high LRIG1 staining intensity or a high percentage of LRIG1-positive cells showed a very good prognosis. Furthermore, LRIG1 expression correlated with HPV status, whereas LRIG2 expression inversely correlated with HPV status.Conclusions:Taken together, the results suggest that LRIG1 immunoreactivity could be a clinically important prognostic marker in HPV-associated oropharyngeal cancer.

  • 29.
    Ling, Agnes
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Edin, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikberg, Maria L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Öberg, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The intratumoural subsite and relation of CD8(+) and FOXP3(+) T lymphocytes in colorectal cancer provide important prognostic clues2014Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 110, nr 10, s. 2551-2559Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To find improved tools for prognostic evaluation in patients with colorectal cancer (CRC), we have analysed how infiltration of cytotoxic T lymphocytes (CD8(+)) and regulatory T lymphocytes (FoxP3(+)) correlates to prognosis, not only according to quantity and relation, but also to subsite within tumours of different molecular characteristics (microsatellite instability and CpG island methylator phenotype status).

    Methods: CD8 and FOXP3 expression was evaluated by immunohistochemistry in 426 archival tumour tissue samples from patients surgically resected for CRC. The average infiltration of CD8(+) and FOXP3(+) cells was assessed along the tumour invasive front, in the tumour centre and within the tumour epithelium (intraepithelial).

    Results: We found that infiltration of CD8(+) T lymphocytes within the tumour epithelium provided the strongest prognostic information (P < 0.001). At the tumour invasive front and tumour centre, FOXP3 expression withheld the strongest association to prognosis (P < 0.001), suggesting FOXP3(+) T-lymphocyte infiltration to be a better prognostic tool than CD8(+) T lymphocytes at these intratumoural subsites. We further analysed the possible prognostic impact of the relation between these T-cell subsets, finding that a high intraepithelial CD8 expression was associated with a better patient outcome, independent of FOXP3 infiltration. In groups of low intraepithelial CD8 expression, however, a high infiltration rate of FOXP3(+) cells at the tumour invasive front, significantly improved prognosis.

    Conclusions: Analyses of intraepithelial infiltration of CD8(+) T lymphocytes, infiltration of FOXP3(+) T lymphocytes at the tumour front or centre, and the relation between these subsets, may be a valuable tool for predicting prognosis in colon cancer.

  • 30. Molina-Montes, Esther
    et al.
    Sanchez, Maria-Jose
    Buckland, Genevieve
    Bueno-de-Mesquita, H. B(as)
    Weiderpass, Elisabete
    Amiano, Pilar
    Wark, Petra A.
    Kuehn, Tilman
    Katzke, Verena
    Maria Huerta, Jose
    Ardanaz, Eva
    Ramon Quiros, Jose
    Affret, Aurelie
    His, Mathilde
    Boutron-Ruault, Marie-Christine
    Peeters, Petra H.
    Ye, Weimin
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Boeing, Heiner
    Iqbal, Khalid
    Ohlsson, Bodil
    Sonestedt, Emily
    Tjonneland, Anne
    Petersen, Kristina E. N.
    Travis, Ruth C.
    Skeie, Guri
    Agnoli, Claudia
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Sacerdote, Carlotta
    Freisling, Heinz
    Huybrechts, Inge
    Overvad, Kim
    Trichopoulou, Antonia
    Bamia, Christina
    Vasilopoulou, Effie
    Wareham, Nick
    Khaw, Kay-Tee
    Cross, Amanda J.
    Ward, Heather A.
    Riboli, Elio
    Duell, Eric J.
    Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort2017Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, nr 6, s. 811-820Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Methods: Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs).

    Results: Adherence to the arMED score was not associated with risk of pancreatic cancer (HR highvs low adherence=0.99; 95% CI: 0.77–1.26, and HR per increments of two units in adherence to arMED=1.00; 95% CI: 0.94–1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern.

    Conclusions: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.

  • 31. Moskal, Aurelie
    et al.
    Freisling, Heinz
    Byrnes, Graham
    Assi, Nada
    Fahey, Michael T.
    Jenab, Mazda
    Ferrari, Pietro
    Tjonneland, Anne
    Petersen, Kristina E. N.
    Dahm, Christina C.
    Plambeck Hansen, Camilla
    Affret, Aurelie
    Boutron-Ruault, Marie-Christine
    Cadeau, Claire
    Kuhn, Tilman
    Katzke, Verena
    Iqbal, Khalid
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    Naska, Androniki
    Masala, Giovanna
    de Magistris, Maria Santucci
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Peeters, Petra H.
    Bueno-De-Mesquita, Bas H.
    Engeset, Dagrun
    Licaj, Idlir
    Skeie, Guri
    Ardanaz, Eva
    Buckland, Genevieve
    Huerta Castano, Jose M.
    Quiros, Jose R.
    Amiano, Pilar
    Molina-Portillo, Elena
    Winkvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, PO Box 459, 40530 Gothenburg, Sweden.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ericson, Ulrika
    Sonestedt, Emily
    Perez-Cornago, Aurora
    Wareham, Nick
    Khaw, Kay-Tee
    Huybrechts, Inge
    Tsilidis, Konstantinos K.
    Ward, Heather
    Gunter, Marc J.
    Slimani, Nadia
    Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study2016Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 115, nr 11, s. 1430-1440Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. Results: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d. = 0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.) = 0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. Conclusions: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.

  • 32.
    Mu, Yabing
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Zang, Guangxiang
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Engstrom, U.
    Busch, C.
    Landstrom, Maréne
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    TGF beta-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells2015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, nr 7, s. 1223-1231Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    The Par complex - comprising partition-defective 6 (Par6), Par3, and atypical protein kinase C (aPKC) - is crucial for cell polarisation, the loss of which contributes to cancer progression. Transforming growth factor beta (TGF beta)-induced phosphorylation of Par6 on the conserved serine 345 is implicated in epithelial-to-mesenchymal transition (EMT) in breast cancer. Here we investigated the importance of phosphorylated Par6 in prostate cancer.

    Methods:

    We generated a p-Par6(345)-specific antibody and verified its specificity in vitro. Endogenous p-Par6(345) was analysed by immunoblotting in normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular localisation of p-Par6(345) in migrating TGF beta-treated PC-3U cells was analysed by confocal imaging. Invasion assays of TGF beta-treated PC-3U cells were performed. p-Par6 expression was immunohistochemically analysed in prostate cancer tissues.

    Results:

    TGF beta induced Par6 phosphorylation on Ser345 and its recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells, where it colocalised with aPKC zeta. The p-Par6-aPKC zeta complex is important for cell migration and invasion, as interference with this complex prevented prostate cancer cell invasion. High levels of activated Par6 correlated with aggressive prostate cancer.

    Conclusions: Increased p-Par6Ser(345) levels in aggressive prostate cancer tissues and cells suggest that it could be a useful novel biomarker for predicting prostate cancer progression.

  • 33. Naucler, P
    et al.
    Ryd, W
    Törnberg, S
    Strand, A
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Hansson, B G
    Rylander, E
    Dillner, J
    HPV type-specific risks of high-grade CIN during 4 years of follow-up: a population-based prospective study.2007Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 97, nr 1, s. 129-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We followed a population-based cohort of 5696 women, 32-38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2+ than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2+. In summary, the different HPV types found in cervical cancer show distinctly different CIN2+ risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33.

  • 34. Obón-Santacana, M.
    et al.
    Kaaks, R.
    Slimani, N.
    Lujan-Barroso, L.
    Freisling, H.
    Ferrari, P.
    Dossus, L.
    Chabbert-Buffet, N.
    Baglietto, L.
    Fortner, R. T.
    Boeing, H.
    Tjønneland, A.
    Olsen, A.
    Overvad, K.
    Menéndez, V.
    Molina-Montes, E.
    Larrañaga, N.
    Chirlaque, M-D
    Ardanaz, E.
    Khaw, K-T
    Wareham, N.
    Travis, R. C.
    Lu, Y.
    Merritt, M. A.
    Trichopoulou, A.
    Benetou, V.
    Trichopoulos, D.
    Saieva, C.
    Sieri, S.
    Tumino, R.
    Sacerdote, C.
    Galasso, R.
    Bueno-de-Mesquita, H. B.
    Wirfalt, E.
    Ericson, U.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Ohlson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Skeie, G.
    Gram, I. T.
    Weiderpass, E.
    Onland-Moret, N. C.
    Riboli, E.
    Duell, E. J.
    Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort2014Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 111, nr 5, s. 987-997Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n = 1382) or type-I EC risk (n = 627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n = 203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.

  • 35.
    Ohlsson, Lina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Israelsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Näslund, L.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Öberg, Å.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Lindmark, G.
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR2006Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 95, nr 2, s. 218-225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT–PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A–D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2.

  • 36.
    Ohlsson, Lina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Lindmark, Gudrun
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Sitohy, Basel
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ectopic expression of the chemokine CXCL17 in colon cancer cells2016Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, nr 6, s. 697-703Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The novel chemokine CXCL17 acts as chemoattractant for monocytes, macrophages and dendritic cells. CXCL17 also has a role in angiogenesis of importance for tumour development. Methods: Expression of CXCL17, CXCL10, CXCL9 and CCL2 was assessed in primary colon cancer tumours, colon carcinoma cell lines and normal colon tissue at mRNA and protein levels by real-time qRT-PCR, immunohistochemistry, two-colour immunofluorescence and immunomorphometry. Results: CXCL17 mRNA was expressed at 8000 times higher levels in primary tumours than in normal colon (P<0.0001). CXCL17 protein was seen in 17.2% of cells in tumours as compared with 0.07% in normal colon (P = 0.0002). CXCL10, CXCL9 and CCL2 mRNAs were elevated in tumours but did not reach the levels of CXCL17. CXCL17 and CCL2 mRNA levels were significantly correlated in tumours. Concordant with the mRNA results, CXCL10-and CXCL9-positive cells were detected in tumour tissue, but at significantly lower numbers than CXCL17. Two-colour immunofluorescence and single-colour staining of consecutive sections for CXCL17 and the epithelial cell markers carcinoembryonic antigen and BerEP4 demonstrated that colon carcinoma tumour cells indeed expressed CXCL17. Conclusions: CXCL17 is ectopically expressed in primary colon cancer tumours. As CXCL17 enhances angiogenesis and attracts immune cells, its expression could be informative for prognosis in colon cancer patients.

  • 37.
    Ohlsson, Lina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Lindmark, G
    Israelsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Öberg, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Lymph node tissue kallikrein-related peptidase 6 mRNA: a progression marker for colorectal cancer.2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, nr 1, s. 150-157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:A most important characteristic feature for poor prognosis in colorectal cancer (CRC) is the presence of lymph node metastasis. Determination of carcinoembryonic antigen (CEA) mRNA levels in lymph nodes has proven powerful for quantification of disseminated tumour cells. Here, we investigate the utility of human tissue kallikrein-related peptidase 6 (KLK6) mRNA as a progression biomarker to complement CEA mRNA, for improved selection of patients in need of adjuvant therapy and intensified follow-up after surgery.Methods:Lymph nodes of pTNM stage I-IV CRC- (166 patients/503 lymph nodes) and control (23/108) patients were collected at surgery and analysed by quantitative RT-PCR.Results:Lymph node KLK6 positivity was an indicator of poor outcome (hazard ratio 3.7). Risk of recurrence and cancer death increased with KLK6 lymph node levels. Patients with KLK6 lymph node levels above the 90th percentile had a hazard ratio of 6.5 and 76 months shorter average survival time compared to patients with KLK6 negative nodes. The KLK6 positivity in lymph nodes with few tumour cells, that is, low CEA mRNA levels, also indicated poor prognosis (hazard ratio 2.8).Conclusion:In CRC patients, lymph node KLK6 positivity indicated presence of aggressive tumour cells associated with poor prognosis and high risk of tumour recurrence.

  • 38. Ose, J.
    et al.
    Fortner, R. T.
    Schock, H.
    Peeters, P. H.
    Onland-Moret, N. C.
    Bueno-de-Mesquita, H. B.
    Weiderpass, E.
    Gram, I. T.
    Overvad, K.
    Tjonneland, A.
    Dossus, L.
    Fournier, A.
    Baglietto, L.
    Trichopoulou, A.
    Benetou, V.
    Trichopoulos, D.
    Boeing, H.
    Masala, G.
    Krogh, V.
    Matiello, A.
    Tumino, R.
    Popovic, M.
    Obon-Santacana, M.
    Larranaga, N.
    Ardanaz, E.
    Sanchez, M-J
    Menendez, V.
    Chirlaque, M-D
    Travis, R. C.
    Khaw, K-T
    Braendstedt, J.
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rinaldi, S.
    Kuhn, E.
    Romieu, I.
    Gunter, M. J.
    Merritt, M. A.
    Riboli, E.
    Kaaks, R.
    Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort2015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, nr 1, s. 162-166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n = 565 cases). Multivariable conditional logistic regression models were used to estimate associations. Results: We observed no association between IGF-I and EOC overall or by tumour characteristics. Conclusions: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.

  • 39. Osorio, A
    et al.
    Milne, R L
    Pita, G
    Peterlongo, P
    Heikkinen, T
    Simard, J
    Chenevix-Trench, G
    Spurdle, A B
    Beesley, J
    Chen, X
    Healey, S
    Neuhausen, S L
    Ding, Y C
    Couch, F J
    Wang, X
    Lindor, N
    Manoukian, S
    Barile, M
    Viel, A
    Tizzoni, L
    Szabo, C I
    Foretova, L
    Zikan, M
    Claes, K
    Greene, M H
    Mai, P
    Rennert, G
    Lejbkowicz, F
    Barnett-Griness, O
    Andrulis, I L
    Ozcelik, H
    Weerasooriya, N
    Gerdes, A-M
    Thomassen, M
    Cruger, D G
    Caligo, M A
    Friedman, E
    Kaufman, B
    Laitman, Y
    Cohen, S
    Kontorovich, T
    Gershoni-Baruch, R
    Dagan, E
    Jernström, H
    Askmalm, M S
    Arver, B
    Malmer, Beatrice
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Domchek, S M
    Nathanson, K L
    Brunet, J
    Ramón Y Cajal, T
    Yannoukakos, D
    Hamann, U
    Hogervorst, F B L
    Verhoef, S
    Gómez García, E B
    Wijnen, J T
    van den Ouweland, A
    Easton, D F
    Peock, S
    Cook, M
    Oliver, C T
    Frost, D
    Luccarini, C
    Evans, D G
    Lalloo, F
    Eeles, R
    Pichert, G
    Cook, J
    Hodgson, S
    Morrison, P J
    Douglas, F
    Godwin, A K
    Sinilnikova, O M
    Barjhoux, L
    Stoppa-Lyonnet, D
    Moncoutier, V
    Giraud, S
    Cassini, C
    Olivier-Faivre, L
    Révillion, F
    Peyrat, J-P
    Muller, D
    Fricker, J-P
    Lynch, H T
    John, E M
    Buys, S
    Daly, M
    Hopper, J L
    Terry, M B
    Miron, A
    Yassin, Y
    Goldgar, D
    Singer, C F
    Gschwantler-Kaulich, D
    Pfeiler, G
    Spiess, A-C
    Hansen, Thomas V O
    Johannsson, O T
    Kirchhoff, T
    Offit, K
    Kosarin, K
    Piedmonte, M
    Rodriguez, G C
    Wakeley, K
    Boggess, J F
    Basil, J
    Schwartz, P E
    Blank, S V
    Toland, A E
    Montagna, M
    Casella, C
    Imyanitov, E N
    Allavena, A
    Schmutzler, R K
    Versmold, B
    Engel, C
    Meindl, A
    Ditsch, N
    Arnold, N
    Niederacher, D
    Deissler, H
    Fiebig, B
    Varon-Mateeva, R
    Schaefer, D
    Froster, U G
    Caldes, T
    de la Hoya, M
    McGuffog, L
    Antoniou, A C
    Nevanlinna, H
    Radice, P
    Benítez, J
    Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)2009Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 101, nr 12, s. 2048-2054Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. METHODS: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. RESULTS: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers. CONCLUSION: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.

  • 40.
    Remes, K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Rosenquist, R
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Mehle, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Lindh, Jack
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Telomere length and telomerase activity in malignant lymphomas at diagnosis and relapse2000Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 82, nr 3, s. 601-607Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Telomere length maintenance, in the vast majority of cases executed by telomerase, is a prerequisite for long-term proliferation. Most malignant tumours, including lymphomas, are telomerase-positive and this activity is a potential target for future therapeutic interventions since inhibition of telomerase has been shown to result in telomere shortening and cell death in vitro. One prerequisite for the suitability of anti-telomerase drugs in treating cancer is that tumours exhibit shortened telomeres compared to telomerase-positive stem cells. A scenario is envisioned where the tumour burden is reduced using conventional therapy whereafter remaining tumour cells are treated with telomerase inhibitors. In evaluating the realism of such an approach it is essential to know the effects on telomere status by traditional therapeutic regimens. We have studied the telomere lengths in 47 diagnostic lymphomas and a significant telomere shortening was observed compared to benign lymphoid tissues. In addition, telomere length and telomerase activity were studied in consecutive samples from patients with relapsing non-Hodgkin's lymphomas. Shortened, unchanged and elongated telomere lengths were observed in the relapse samples. The telomere length alterations found in the relapsing lymphomas appeared to be independent of telomerase and rather represented clonal selection random at the telomere length level. These data indicate that anti-telomerase therapy would be suitable in only a fraction of malignant lymphomas.

  • 41. Rohrmann, S
    et al.
    Grote, VA
    Becker, S
    Rinaldi, S
    Tjonneland, A
    Roswall, N
    Gronbaek, H
    Overvad, K
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Racine, A
    Teucher, B
    Boeing, H
    Drogan, D
    Dilis, V
    Lagiou, P
    Trichopoulou, A
    Palli, D
    Tagliabue, G
    Tumino, R
    Vineis, P
    Mattiello, A
    Rodriguez, L
    Duell, EJ
    Molina-Montes, E
    Dorronsoro, M
    Huerta, J-M
    Ardanaz, E
    Jeurnink, S
    Peeters, PHM
    Lindkvist, B
    Johansen, D
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Ye, W
    Khaw, K-T
    Wareham, NJ
    Allen, NE
    Crowe, FL
    Fedirko, V
    Jenab, M
    Michaud, DS
    Norat, T
    Riboli, E
    Bueno-de-Mesquita, HB
    Kaaks, R
    Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition2012Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, nr 5, s. 1004-1010Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.

    METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables.

    RESULTS: Neither circulating levels of IGF-I (OR = 1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR = 1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR = 1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR = 1.72, 95% CI 1.05-2.83; P-interaction = 0.154).

    CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

    British Journal of Cancer (2012) 106, 1004-1010. doi:10.1038/bjc.2012.19 www.bjcancer.com Published online 7 February 2012 (C) 2012 Cancer Research UK

  • 42. Rohrmann, S.
    et al.
    Linseisen, J.
    Allen, N.
    Bueno-de-Mesquita, H. B.
    Johnsen, N. F.
    Tjonneland, A.
    Overvad, K.
    Kaaks, R.
    Teucher, B.
    Boeing, H.
    Pischon, T.
    Lagiou, P.
    Trichopoulou, A.
    Trichopoulos, D.
    Palli, D.
    Krogh, Vittorio
    Tunnino, R.
    Ricceri, F.
    Argueelles Suarez, M. V.
    Agudo, A.
    Sanchez, M-J
    Chirlaque, M-D
    Barricarte, A.
    Larranaga, N.
    Boshuizen, H.
    van Kranen, H. J.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Johansson, M.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Bjartell, A.
    Ulmert, D.
    Khaw, K-T
    Wareham, N. J.
    Ferrari, Pietro
    Romieux, I.
    Gunter, M. J. R.
    Riboli, Elio
    Key, T. J.
    Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition2013Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, nr 3, s. 708-714Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR = 0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR = 1.81, 95% CI: 1.11-2.93; RR = 1.38, 95% CI: 1.01-1.87, respectively). Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.

  • 43. Rosell, Johan
    et al.
    Nordenskjöld, B
    Bengtsson, Nils-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Fornander, T
    Hatschek, T
    Lindman, H
    Malmström, P-O
    Wallgren, A
    Stål, O
    Carstensen, J
    Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial2011Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, nr 6, s. 899-902Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:  

    Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease.

    Methods:  

    Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression.

    Results:  

    Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05–2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63–0.96), and the difference in HR between the two time-periods was significant (P=0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03–9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40–0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke.

    Conclusion:  

    In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period.

  • 44.
    Sandström, Maria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Andersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Patologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model2004Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 91, nr 6, s. 1174-1180Artikel i tidskrift (Refereegranskat)
  • 45. Sen, Abhijit
    et al.
    Tsilidis, Konstantinos K.
    Allen, Naomi E.
    Rinaldi, Sabina
    Appleby, Paul N.
    Almquist, Martin
    Schmidt, Julie A.
    Dahm, Christina C.
    Overvad, Kim
    Tjonneland, Anne
    Rostgaard-Hansen, Agnetha L.
    Clavel-Chapelon, Francoise
    Baglietto, Laura
    Boutron-Ruault, Marie-Christine
    Kuehn, Tilman
    Katze, Verena A.
    Boeing, Heiner
    Trichopoulou, Antonia
    Tsironis, Christos
    Lagiou, Pagona
    Palli, Domenico
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, H. B. (as)
    Peeters, Petra H.
    Hjartaker, Anette
    Lund, Eiliv
    Weiderpass, Elisabete
    Ramon Quiros, J.
    Agudo, Antonio
    Sanchez, Maria-Jose
    Arriola, Larraitz
    Gavrila, Diana
    Barricarte Gurrea, Aurelio
    Tosovic, Ada
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Romieu, Isabelle
    Ferrari, Pietro
    Zamora-Ros, Raul
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Riboli, Elio
    Gunter, Marc
    Franceschi, Silvia
    Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study2015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 113, nr 5, s. 840-847Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Results from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered.

    Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models.

    Results: Compared with participants consuming 0.1-4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1-1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR = 0.77; 95% CI = 0.60-0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes.

    Conclusions: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas.

  • 46.
    Sgaramella, Nicola
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Naples, Italy.
    Coates, P. J.
    Dundee, U.K..
    Strindlund, K.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Loljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Colella, G.
    Naples, Italy.
    Laurell, G.
    Uppsala, Sweden.
    Rossiello, R.
    Naples, Italy.
    Muzio, L. L.
    Foggia, Italy.
    Loizou, Christos
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Tartaro, G.
    Naples, Italy.
    Olofsson, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Danielsson, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Fåhraeus, R.
    Brno, Czech Republic; Paris, France.
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-12015Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 113, nr 2, s. 321-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged <= 40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.

  • 47. Singel, Kelly L.
    et al.
    Grzankowski, Kassondra S.
    Khan, A. N. M. Nazmul H.
    Grimm, Melissa J.
    D'Auria, Anthony C.
    Morrell, Kayla
    Eng, Kevin H.
    Hylander, Bonnie
    Mayor, Paul C.
    Emmons, Tiffany R.
    Lénárt, Nikolett
    Fekete, Rebeka
    Környei, Zsuzsanna
    Muthukrishnan, Uma
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Gilthorpe, Jonathan D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Urban, Constantin F.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Itagaki, Kiyoshi
    Hauser, Carl J.
    Leifer, Cynthia
    Moysich, Kirsten B.
    Odunsi, Kunle
    Dénes, Ádám
    Segal, Brahm H.
    Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer2019Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 120, nr 2, s. 207-217Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Advanced cancer causes necrosis and releases damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs activate neutrophils, including generation of neutrophil extracellular traps (NETs), which are injurious, thrombogenic, and implicated in metastasis. We hypothesised that extracellular mitochondrial DNA (mtDNA) in ascites from patients with epithelial ovarian cancer (EOC) would correlate with worse outcomes.

    METHODS: Banked ascites supernatants from patients with newly diagnosed advanced EOC were analysed for mtDNA, neutrophil elastase, and activation of healthy donor neutrophils and platelets. TCGA was mined for expression of SELP and ELANE.

    RESULTS: The highest quartile of ascites mtDNA correlated with reduced progression-free survival (PFS) and a higher likelihood of disease progression within 12-months following primary surgery (n = 68, log-rank, p = 0.0178). NETs were detected in resected tumours. Ascites supernatants chemoattracted neutrophils, induced NETs, and activated platelets. Ascites exposure rendered neutrophils suppressive, based on abrogation of ex vivo stimulated T cell proliferation. Increased SELP mRNA expression correlated with worse overall survival (n = 302, Cox model, p = 0.02).

    CONCLUSION: In this single-centre retrospective analysis, ascites mtDNA correlated with worse PFS in advanced EOC. Mitochondrial and other DAMPs in ascites may activate neutrophil and platelet responses that facilitate metastasis and obstruct anti-tumour immunity. These pathways are potential prognostic markers and therapeutic targets.

  • 48.
    Sitaram, Raviprakash T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Andersson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Oji, Y
    Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
    Sugiyama, H
    Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
    Roos, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Li, Ai-Hong
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Wilms' tumour 1 can suppress hTERT gene expression and telomerase activity in clear cell renal cell carcinoma via multiple pathways2010Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 103, nr 8, s. 1255-1262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Wilms' tumour 1 (WT1) gene was discovered as a tumour suppressor gene. Later findings have suggested that WT1 also can be oncogenic. This complexity is partly explained by the fact that WT1 has a number of target genes.

    METHOD: WT1 and its target gene human telomerase reverse transcriptase (hTERT) were analysed in clear cell renal cell carcinoma (ccRCC). In vitro experiments were performed to examine the functional link between WT1 and hTERT by overexpression of WT1 isoforms in the ccRCC cell line, TK-10.

    RESULTS: WT1 demonstrated lower RNA expression in ccRCC compared with renal cortical tissue, whereas hTERT was increased, showing a negative correlation between WT1 and hTERT (P=0.005). These findings were experimentally confirmed in vitro. The WT1 generated effect on hTERT promoter activity seemed complex, as several negative regulators of hTERT transcription, such as SMAD3, JUN (AP-1) and ETS1, were activated by WT1 overexpression. Downregulation of potential positive hTERT regulators, such as cMyc, AP-2α, AP-2γ, IRF1, NFX1 and GM-CSF, were also observed. Chromatin immunoprecipitation analysis verified WT1 binding to the hTERT, cMyc and SMAD3 promoters.

    CONCLUSION: The collected data strongly indicate multiple pathways for hTERT regulation by WT1 in ccRCC.

  • 49. Stendahl, M
    et al.
    Kronblad, Å
    Rydén, L
    Emdin, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Bengtsson, Nils-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Landberg, G
    Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients2004Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 90, nr 10, s. 1942-1948Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antioestrogen treatment by tamoxifen is a well-established adjuvant therapy for oestrogen receptor-alpha (ER) positive breast cancer. Despite ER expression some tumours do not respond to tamoxifen and we therefore delineated the potential link between the cell cycle regulator and ERco-factor, cyclin D1, and tamoxifen response in a material of 167 postmenopausal breast cancers arranged in a tissue array. The patients had been randomised to 2 years of tamoxifen treatment or no treatment and the median follow-up time was 18 years. Interestingly in the 55 strongly ERpositive samples with moderate or low cyclin D1 levels, patients responded to tamoxifen treatment whereas the 46 patients with highly ER positive and cyclin D1 overexpressing tumours did not show any difference in survival between tamoxifen and no treatment. Survival in untreated patients with cyclin D1 high tumours was slightly better than for patients with cyclin D1 low/moderate tumours. However, there was a clearly increased risk of death in the cyclin D1 high group compared to an age-matched control population. Our results suggest that cyclin D1 overexpression predicts for tamoxifen treatment resistance in breast cancer, which is line with recent experimental data using breast cancer cell lines and overexpression systems.

  • 50. Stepien, Magdalena
    et al.
    Hughes, David J.
    Hybsier, Sandra
    Bamia, Christina
    Tjønneland, Anne
    Overvad, Kim
    Affret, Aurélie
    His, Mathilde
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Kuehn, Tilman
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Lagiou, Pagona
    Orfanos, Phlippos
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Ricceri, Fulvio
    Panico, Salvatore
    Bueno-de-Mesquita, H. B. (as)
    Peeters, Petra H.
    Weiderpass, Elisabete
    Lasheras, Cristina
    Bonet Bonet, Catalina
    Molina-Portillo, Elena
    Dorronsoro, Miren
    Maria Huerta, José
    Barricarte, Aurelio
    Ohlsson, Bodil
    Sjöberg, Klas
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wareham, Nick
    Khaw, Kay-Tee
    Travis, Ruth C.
    Freisling, Heinz
    Cross, Amanda J.
    Schomburg, Lutz
    Jenab, Mazda
    Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans2017Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, nr 5, s. 688-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n = 106, IHDB n = 34, GBTC n = 96) and their matched controls (1: 1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. Results: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR = 0.36; 95% CI: 0.13-0.98, Ptrend = 0.0123), but no association for copper (OR = 1.06; 95% CI: 0.45-2.46, Ptrend = 0.8878) in multivariable models. The calculated Cu/ Zn ratio showed a positive association for HCC (OR = 4.63; 95% CI: 1.41-15.27, Ptrend = 0.0135). For IHBC and GBTC, no significant associations were observed. Conclusions: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

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