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  • 1.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sundkvist, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Fuchs, Klara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Zingmark, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Löfgren Burström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Plasma concentrations of gut hormones acyl ghrelin and peptide YY and subsequent risk of colorectal cancer and molecular tumor subtypes2023Ingår i: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 16, nr 2, s. 75-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity and metabolic dysfunction are implicated in colorectal cancer development. Appetite-regulating gut hormones might have a role in colorectal cancer risk. We investigated whether circulating levels of the gut hormones ghrelin (analyzed as acyl ghrelin) and Peptide YY (PYY) were associated with subsequent colorectal cancer risk, including clinical and molecular tumor subtypes. We also provide descriptive data on these hormones in relation to background participant characteristics and metabolic biomarkers. This population-based study included 1,010 matched case-control pairs with a median of 12.3 years of follow-up. Acyl ghrelin and PYY were measured by multiplex immunoassay. Data on KRAS and BRAF mutations and microsatellite instability (MSI) status were available for 704 and 708 cases, respectively. Conditional logistic regression models estimated association to colorectal cancer risk. Partial correlation and linear regression were used to investigate relationships between background and metabolic variables and variation in plasma gut hormone concentrations. Acyl ghrelin was not clearly associated with colorectal cancer risk (multivariable OR per 1 SD increase: 1.11; 95% CI, 1.00-1.23). Positive associations were observed for specific subtypes, in particular BRAF-mutated colorectal cancer and right-sided colon cancer, although with nonsignificant heterogeneity. PYY was not related to colorectal cancer risk (multivariable OR per 1 SD: 1.04; 95% CI, 0.95-1.14) or any tumor subtype. In the control participants, ghrelin was inversely correlated with BMI, and PYY was positively correlated with C-peptide and insulin levels. These findings provide limited support for a possible role for ghrelin in colorectal cancer development, primarily in specific anatomical and molecular tumor subtypes.

    PREVENTION RELEVANCE: The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.

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  • 2.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Sundkvist, Anneli
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Zingmark, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Löfgren Burström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer2020Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, nr 7, s. 1482-1491Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Inflammation has been implicated in colorectal cancer etiology, but the relationship between C-reactive protein (CRP) and colorectal cancer risk is unclear. We aimed to investigate the association between prediagnostic plasma CRP concentrations and the risk of clinical and molecular colorectal cancer subtypes.

    Methods: We used prospectively collected samples from 1,010 matched colorectal cancer case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of colorectal cancer, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag time, and (using unconditional logistic regression) body mass index.

    Results: CRP was not associated with colorectal cancer risk, regardless of clinical or molecular colorectal cancer subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk [OR per 1 unit increase in natural logarithm (In) transformed CRP, 1.32; 95% confidence interval (CI), 1.01-1.73]. CRP levels increased over time, but average time trajectories were similar for cases and controls (P-interaction = 0.19).

    Conclusions: Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in colorectal cancer etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Impact: Future efforts to establish the putative role of chronic, low-grade inflammation in colorectal cancer development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.

  • 3.
    Dimou, Niki
    et al.
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Mori, Nagisa
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Martin, Richard M.
    MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Bristol, United Kingdom; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom.
    Smith-Byrne, Karl
    Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
    Papadimitriou, Nikos
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Timothy Bishop, D.
    Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.
    Casey, Graham
    Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States.
    Colorado-Yohar, Sandra M.
    Department of Epidemiology, Murcia Regional Health Council, IMIBArrixaca, Murcia, Spain; CIBER Epidemiología y Salud Publica (CIBERESP), Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
    Cotterchio, Michelle
    Ontario Health (Cancer Care Ontario), ON, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, ON, Toronto, Canada.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London, United Kingdom.
    Le Marchand, Loic
    University of Hawaii Cancer Center, HI, Honolulu, United States.
    Lin, Yi
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States.
    Offit, Kenneth
    Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, NY, New York, United States; Department of Medicine, Weill Cornell Medical College, NY, New York, United States.
    Charlotte Onland-Moret, N.
    Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
    Peters, Ulrike
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States.
    Potter, John D.
    Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States; Centre for Public Health Research, Massey University, Wellington, New Zealand.
    Rohan, Thomas E.
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, Bronx, United States.
    Weiderpass, Elisabete
    Office of the Director, International Agency for Research on Cancer, Lyon, France.
    Gunter, Marc J.
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Murphy, Neil
    Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
    Circulating levels of testosterone, sex hormone binding globulin and colorectal cancer risk: Observational and mendelian randomization analyses2021Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, nr 7, s. 1336-1348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses.

    Methods: The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR.

    Results: In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational andMRanalyses.

    Conclusions: Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development.

  • 4.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Circulating markers of risk and etiology in colorectal cancer2023Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Colorectal cancer is the third most commonly diagnosed cancer in men and women. Worldwide around 2 million individuals are diagnosed each year – a number expected to increase as colorectal cancer risk factors become more prevalent. In men and women there is a difference in incidence, which possibly could be explained by inherent differences, including sex hormone profiles. The prognosis of colorectal cancer is highly dependent on the stage at diagnosis, with individuals diagnosed at early stages having the best long-term survival. However, as onset of symptoms can be diffuse, many individuals are diagnosed at later stages when survival rates are significantly poorer. Therefore, screening and prevention strategies to detect colorectal cancer at earlier stages or remove cancer precursors such as polyps may be key to increasing survival. Commonly used screening tools today include fecal blood tests and colonoscopy, but they have modest accuracy or may not be cost-effective. Being able to identify markers in blood, either for early detection, as a complementary or alternative screening method, or for risk stratification, could aid in solving this problem. 

    Aim: The overall of aim of the thesis was to improve our understanding of underlying factors contributing to CRC etiology and to find biomarkers associated with CRC that could aid in the future development of effective risk prediction models. 

    Methods: All studies included in this thesis were based on a case-control cohort nested within the Northern Sweden Health and Disease Study (NSHDS). Additionally in paper I, we also used data from the European Prospective Investigation into Cancer and Nutrition (EPIC), a large multi-center cohort study. In this paper we examined associations between sex hormones, sex hormone binding globulin (SHBG), and colon cancer in men. The study included 690 colon cancer cases and 690 matched controls. Paper II was a longitudinal study, using repeated samples from 80 men, on circulating sex hormones, SHBG, and DNA methylation in white blood cells. Papers III and IV were nested case-control studies on proteins and colorectal cancer risk with Paper III divided into a discovery and a validation phase. In the first phase, which included 69 colorectal cancer case-control pairs with repeated samples, 160 unique proteins related to inflammation and oncology were analyzed. In the second phase, 13 proteins that were significantly associated with colorectal cancer risk, together with 8 proteins identified from the literature, were measured on a custom panel, and validated in a larger material consisting of 1000 case-control pairs. In paper IV, which included 195 colorectal cancer case-control pairs, the protein analysis was extended to include 1536 proteins linked to oncology, inflammation, neurology, and metabolism. In papers using a matched case-control design, conditional i logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations. For longitudinal analyses, mixed effects models were used to estimate associations. 

    Results: In paper I, we observed a statistically significant inverse association between circulating levels of testosterone and colon cancer. For SHBG there was a statistically significant inverse association prior to adjustment of testosterone and estradiol levels. In paper II, we found one novel genome-wide significant association between circulating levels of dehydroepiandrosterone and DNA methylation at the cg14319657 CpG site. In addition, we also identified more than 40 differentially methylated regions associated with levels of sex hormones and SHBG. In paper III, we first identified 13 proteins associated with CRC risk in the discovery phase. In the validation phase, however, none of the proteins remained significantly associated with colorectal cancer. When stratifying by tumor site, FGF-21 and PPY, were statically significant in colon and rectal cancer respectively, and showed some modest increase in predictive performance. In paper IV, we identified 20 proteins surpassing a significance threshold of 0.005. One protein, TFF3 (Trefoil Factor 3), which was positively associated with colorectal, also withstood strict Bonferroni correction. In addition, we validated several proteins, including AREG, CEA, and LGALS4, which were identified as biomarker candidates in previous studies. 

    Conclusions: Our results support the hypothesis that circulating sex hormones play a role in male colon cancer etiology and that this may partly explain the difference in colorectal cancer incidence between men and women. Furthermore, our findings suggest a possible link between circulating sex hormones, SHBG and DNA methylation, which could be of interest in the etiology of colorectal cancer as well as other hormone-dependent diseases. Finally, we also identified several proteins associated with colorectal cancer, some of which have shown potential as screening markers. 

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  • 5.
    Harbs, Justin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rentoft, Matilda
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Melin, Beatrice S.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gylling, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Identifying prediagnostic colorectal cancer biomarkers using a targeted proteomics platform with extensive coverageManuskript (preprint) (Övrigt vetenskapligt)
  • 6.
    Harbs, Justin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rinaldi, Sabina
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Gicquiau, Audrey
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Keski-Rahkonen, Pekka
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Mori, Nagisa
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Liu, Xijia
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Katzke, Verena
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy.
    Bueno-De-Mesquita, Bas
    Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
    Crous-Bou, Marta
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Sánchez, Maria-Jose
    Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Aizpurua, Amaia
    Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Spain.
    Chirlaque, María-Dolores
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Gurrea, Aurelio Barricarte
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Travis, Ruth C.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Watts, Eleanor L.
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Christakoudi, Sofia
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; MRC Centre for Transplantation, Division of Transplantation Immunology and Mucosal Biology, Faculty of Life Sciences & Medicine, King’s College London, London, United Kingdom.
    Tsilidis, Konstantinos K.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, Faculty of Medicine, University of Ioannina School of Medicine, Ioannina, Greece.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Gunter, Marc J.
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Murphy, Neil
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case–Control Study and Meta-Analysis2022Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 31, nr 4, s. 793-803Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking.

    Methods: We conducted a comprehensive nested case–control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men.

    Results: Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51–0.89) and SHBG (OR, 0.77; 95% CI, 0.62–0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58–1.18). In a dose–response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL ¼ 0.98; 95% CI, 0.96–1.00; I2 ¼ 22%] and free testosterone (RR per 1 ng/dL ¼ 0.98; 95% CI, 0.95–1.00; I2 ¼ 0%).

    Conclusions: Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development.

    Impact: Additional support for the involvement of sex hormones in male colon cancer.

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  • 7.
    Harbs, Justin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rinaldi, Sabina
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Keski-Rahkonen, Pekka
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Liu, Xijia
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples2023Ingår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 18, nr 1, artikel-id 2196759Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their interrelationships could provide new insights into the pathology of disease development. We, therefore, investigated associations between circulating sex hormones, sex hormone binding globulin (SHBG), and DNA methylation in blood, using samples from 77 men (65 with repeated samples), from the population-based Northern Sweden Health and Disease Study (NSHDS). DNA methylation was measured in buffy coat using the Infinium Methylation EPIC BeadChip (Illumina). Sex hormone (oestradiol, oestrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) and SHBG concentrations were measured in plasma using a high-performance liquid chromatography tandem mass spectrometry (LC/MS-MS) method and an enzyme-linked immunoassay, respectively. Associations between sex hormones, SHBG, and DNA methylation were estimated using both linear regression and mixed-effects models. Additionally, we used the comb-p method to identify differentially methylated regions based on nearby P values. We identified one novel CpG site (cg14319657), at which DNA methylation was associated with dehydroepiandrosterone, surpassing a genome-wide significance level. In addition, more than 40 differentially methylated regions were associated with levels of sex hormones and SHBG and several of these mapped to genes involved in hormone-related diseases. Our findings support a relationship between circulating sex hormones and DNA methylation and suggest that further investigation is warranted, both for validation, further exploration and to gain a deeper understanding of the mechanisms and potential consequences for health and disease.

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  • 8.
    Harlid, Sophia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brunius, Carl
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Chalmers Mass Spectrometry Infrastructure, Chalmers University of Technology, Gothenburg, Sweden.
    Gunter, Marc J.
    Section of Nutrition and Metabolism, International Agency for Research On Cancer, World Health Organization, Lyon, France.
    Palmqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Liu, Xijia
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 5151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Colorectal cancer prognosis is dependent on stage, and measures to improve early detection are urgently needed. Using prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study, we evaluated protein biomarkers in relation to colorectal cancer risk. Applying a two-tiered approach, we analyzed 160 proteins in matched sequential samples from 58 incident colorectal cancer case–control pairs. Twenty-one proteins selected from both this discovery phase and the literature were then analyzed in a validation set of 450 case–control pairs. Odds ratios were estimated by conditional logistic regression. LASSO regression and ROC analysis were used for multi-marker analyses. In the main validation analysis, no proteins retained statistical significance. However, exploratory subgroup analyses showed associations between FGF-21 and colon cancer risk (multivariable OR per 1 SD: 1.23 95% CI 1.03–1.47) as well as between PPY and rectal cancer risk (multivariable OR per 1 SD: 1.47 95% CI 1.12–1.92). Adding protein markers to basic risk predictive models increased performance modestly. Our results highlight the challenge of developing biomarkers that are effective in the asymptomatic, prediagnostic window of opportunity for early detection of colorectal cancer. Distinguishing between cancer subtypes may improve prediction accuracy. However, single biomarkers or small panels may not be sufficient for effective precision screening.

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  • 9. Mori, Nagisa
    et al.
    Keski-Rahkonen, Pekka
    Gicquiau, Audrey
    Rinaldi, Sabina
    Dimou, Niki
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Aune, Dagfinn
    Cross, Amanda J.
    Tsilidis, Konstantinos K.
    Severi, Gianluca
    Kvaskoff, Marina
    Fournier, Agnès
    Kaaks, Rudolf
    Turzanski Fortner, Renée
    Schulze, Matthias B.
    Jakszyn, Paula
    Sánchez, Maria-Jose
    Colorado-Yohar, Sandra M.
    Ardanaz, Eva
    Travis, Ruth
    Watts, Eleanor L.
    Masala, Giovanna
    Krogh, Vittorio
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Gram, Inger Torhild
    Waaseth, Marit
    Gunter, Marc J.
    Murphy, Neil
    Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis2021Ingår i: JNCI cancer spectrum, ISSN 2515-5091, Vol. 5, nr 6, artikel-id pkab084Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.

    Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.

    Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment=1.17 [95% confidence interval=1.00 to 1.38]; odds ratioquartile4-quartile1 =1.33 [95% confidence interval=0.89 to 1.97], P trend =.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk.

    Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.

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  • 10.
    Nimptsch, Katharina
    et al.
    Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
    Aleksandrova, Krasimira
    Department Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany; Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany.
    Pham, Thu Thi
    Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin, Germany.
    Papadimitriou, Nikos
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Janke, Jürgen
    Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany.
    Christakoudi, Sofia
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Inflammation Biology, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom.
    Heath, Alicia
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Olsen, Anja
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Århus, Århus, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutehtal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Katzke, Verena
    Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Kaaks, Rudolf
    Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Palli, Domenico
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
    Macciotta, Alessandra
    Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
    Pasanisi, Fabrizio
    Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
    Yohar, Sandra Milena Colorado
    Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
    Guevara, Marcela
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Instituto de Salud Pública de Navarra, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
    Amiano, Pilar
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastián, Spain.
    Grioni, Sara
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
    Jakszyn, Paula Gabriela
    Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
    Figueiredo, Jane C.
    Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, CA, Los Angeles, United States.
    Samadder, N. Jewel
    Division of Gastroenterology and Hepatology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, AZ, Phoenix, United States.
    Li, Christopher I.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States.
    Moreno, Victor
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine and Health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L’Hospitalet de Llobregat, Barcelona, Spain.
    Potter, John D.
    Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
    Schoen, Robert E.
    Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, PA, Pittsburgh, United States.
    Um, Caroline Y.
    Department of Population Science, American Cancer Society, GA, Atlanta, United States.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Jenab, Mazda
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Gunter, Marc J.
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Pischon, Tobias
    Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany.
    Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer2023Ingår i: BMC Medicine, E-ISSN 1741-7015, Vol. 21, nr 1, artikel-id 391Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach.

    Methods: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry.

    Results: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37).

    Conclusions: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.

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  • 11.
    Pham, Thu-Thi
    et al.
    Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
    Nimptsch, Katharina
    Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
    Aleksandrova, Krasimira
    Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany; Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany.
    Jenab, Mazda
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, Lyon, France.
    Reichmann, Robin
    Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany.
    Wu, Kana
    Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Kyrø, Cecilie
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Schulze, Matthias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
    Kaaks, Rudolf
    Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Katzke, Verena
    Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Palli, Domenico
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
    Pasanisi, Fabrizio
    Dipartimento di Medicina Clinica E Chirurgia, Federico Ii University, Naples, Italy.
    Ricceri, Fulvio
    Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy; Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, Italy.
    Tumino, Rosario
    Hyblean Association for Epidemiological Research, AIRE ONLUS, Ragusa, Italy.
    Krogh, Vittorio
    Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Venezian 1, Milan, Italy.
    Roodhart, Jeanine
    Department of Medical Oncology, UMC Utrecht, Utrecht, Netherlands.
    Castilla, Jesús
    Navarra Public Health Institute—IdiSNA, Pamplona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
    Sánchez, Maria-Jose
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Colorado-Yohar, Sandra Milena
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rutegård, Martin
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Papier, Keren
    Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Aglago, Elom K.
    Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
    Dimou, Niki
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, Lyon, France.
    Mayen-Chacon, Ana-Lucia
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, 150 Cours Albert Thomas, Lyon, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Pischon, Tobias
    Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Biobank Technology Platform, Berlin, Germany; Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Core Facility Biobank, Berlin, Germany.
    Pre-diagnostic circulating resistin concentrations are not associated with colorectal cancer risk in the european prospective investigation into cancer and nutrition study2022Ingår i: Cancers, ISSN 2072-6694, Vol. 14, nr 22, artikel-id 5499Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Resistin is a polypeptide implicated in inflammatory processes, and as such could be linked to colorectal carcinogenesis. In case-control studies, higher resistin levels have been found in colorectal cancer (CRC) patients compared to healthy individuals. However, evidence for the association between pre-diagnostic resistin and CRC risk is scarce. We investigated pre-diagnostic resistin concentrations and CRC risk within the European Prospective Investigation into Cancer and Nutrition using a nested case-control study among 1293 incident CRC-diagnosed cases and 1293 incidence density-matched controls. Conditional logistic regression models controlled for matching factors (age, sex, study center, fasting status, and women-related factors in women) and potential confounders (education, dietary and lifestyle factors, body mass index (BMI), BMI-adjusted waist circumference residuals) were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for CRC. Higher circulating resistin concentrations were not associated with CRC (RR per doubling resistin, 1.11; 95% CI 0.94–1.30; p = 0.22). There were also no associations with CRC subgroups defined by tumor subsite or sex. However, resistin was marginally associated with a higher CRC risk among participants followed-up maximally two years, but not among those followed-up after more than two years. We observed no substantial correlation between baseline circulating resistin concentrations and adiposity measures (BMI, waist circumference), adipokines (adiponectin, leptin), or metabolic and inflammatory biomarkers (C-reactive protein, C-peptide, high-density lipoprotein cholesterol, reactive oxygen metabolites) among controls. In this large-scale prospective cohort, there was little evidence of an association between baseline circulating resistin concentrations and CRC risk in European men and women.

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  • 12.
    Singleton, Rosie K.
    et al.
    School of Public Health, Imperial College London, London, United Kingdom.
    Heath, Alicia K.
    School of Public Health, Imperial College London, London, United Kingdom.
    Clasen, Joanna L.
    School of Public Health, Imperial College London, London, United Kingdom.
    Scelo, Ghislaine
    Cancer Epidemiology Unit, University of Turin, Turin, Italy.
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    Le Calvez-Kelm, Florence
    International Agency for Research on Cancer, Lyon, France.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, Lyon, France.
    Liedberg, Fredrik
    Institution of Translational Medicine, Lund University, Malmo, Sweden.
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Harbs, Justin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Olsen, Anja
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Århus, Århus, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Dahm, Christina C.
    Department of Public Health, Aarhus University, Denmark.
    Kaaks, Rudolf
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Fortner, Renee T.
    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Panico, Salvatore
    Department of Clinical and Surgical Medicine, Federico II University, Naples, Italy.
    Tagliabue, Giovanna
    Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
    Masala, Giovanna
    Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network–ISPRO, Florence, Italy.
    Tumino, Rosario
    Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy.
    Ricceri, Fulvio
    Department of Clinical and Biological Sciences, University of Turin, Orbassano (TO), Italy; Unit of Epidemiology Regional Health Service ASL TO3, Grugliasco (TO), Italy.
    Gram, Inger T.
    Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, Arctic University of Norway, Tromsø, Norway.
    Santiuste, Carmen
    Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain; CIBER Epidemiología y Salud Publica (CIBERESP), Spain.
    Bonet, Catalina
    Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Barcelona, Spain.
    Rodriguez-Barranco, Miguel
    Escuela Andaluza de Salud Publica (EASP), Granada, Madrid, Spain; Instituto de Investigacion Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigacion Biomedicaen Red de Epidemiología y Salud Publica (CIBERESP), Madrid, Spain.
    Schulze, Mattias B.
    Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DifE), Potsdam, Germany; Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany.
    Bergmann, Manuela M.
    Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrucke (DifE), Potsdam, Germany.
    Travis, Ruth C.
    Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Tzoulaki, Ioanna
    School of Public Health, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom; University of Ioannina Medical School, Ioannina, Greece.
    Riboli, Elio
    School of Public Health, Imperial College London, London, United Kingdom.
    Muller, David C.
    School of Public Health, Imperial College London, London, United Kingdom.
    Risk prediction for renal cell Carcinoma: Results from the European Prospective Investigation into Cancer and nutrition (EPIC) prospective cohort study2021Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, nr 3, s. 507-512Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives. Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure. Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679–0.721]). Our model had slightly improved discrimination (0.714 [0.694–0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025. Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population. Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.

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