649 results on '"Anssi Auvinen"'
Search Results
2. Improving cancer incidence evaluation through local government area matching: a study of the Edo-Benin cancer registry in Nigeria
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Gregrey A. Oko-oboh, Anssi Auvinen, Darlington E. Obaseki, and Janne Pitkäniemi
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Cancer registration ,Local Government Area ,Incidence ,Edo-Benin ,Nigeria ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Cancer registries in Nigeria, as well as in other sub-Saharan African countries, face challenges in adhering to international cancer registration standards. We aimed to improve cancer incidence estimation by identifying under-reporting of new cancers through matching patient-reported local government areas (LGAs) in Edo state, Nigeria, to their respective catchment populations. Methods Information on cancers was obtained from records of hospitals, medical clinics, pathology laboratories, and death certificates according to IARC guidelines. We utilized normalized scores to establish consistency in the number of cancers by calendar time, and standardized incidence ratios (SIR) to assess the variation in cancer incidence across LGAs compared to Edo state average. Subsequently, we estimated sex- and site-specific annual incidence using the average number of cancers from 2016 to 2018 and the predicted mid-year population in three LGAs. Age-standardization was performed using the direct method with the World Standard Population of 1966. Results The number of incident cancers consistent between 2016–2018 in Egor, Oredo, and Uhunmwonde showed a significantly increased SIR. From 2016 to 2018 in these three LGAs, 1,045 new cancers were reported, with 453 (42.4%) in males and 592 (57.6%) in females. The average annual age-standardized incidence rate (ASR) was 50.6 (95% CI: 45.2 – 56.6) per 105. In men, the highest incidence was prostate cancer (ASR: 22.4 per 105), and in women, it was breast cancer (ASR: 16.5 per 105), and cervical cancer (ASR: 12.0 per 105). Microscopically verified cancers accounted for 98.1%. Conclusions We found lower age-standardized incidence rates than those reported earlier for the Edo state population. Collecting information on the local government areas of the cancers allows better matching with the respective target population. We recommend using LGA information to improve the evaluation of population-based cancer incidence in sub-Saharan countries.
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- 2024
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3. Survivorship Data in Prostate Cancer: Where Are We and Where Do We Need To Be?
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Beth Russell, Katharina Beyer, Ailbhe Lawlor, Monique J. Roobol, Lionne D.F. Venderbos, Sebastiaan Remmers, Erik Briers, Sara J. MacLennan, Steven MacLennan, Muhammad Imran Omar, Mieke Van Hemelrijck, Emma Smith, James N'Dow, Karin Plass, Maria Ribal, Nicolas Mottet, Robert Shepherd, Tom Abbott, Ken Mastris, Lisa Moris, Michael Lardas, Thomas Van den Broeck, Peter-Paul Willemse, Nicola Fossati, Karl Pang, Riccardo Campi, Isabella Greco, Mauro Gacci, Sergio Serni, Anders Bjartell, Ragnar Lonnerbro, Alberto Briganti, Daniele Crosti, Roberto Garzonio, Giorgio Gandaglia, Martina Faticoni, Grant office, Chris Bangma, Maria Jongerden, Derya Tilki, Anssi Auvinen, Teemu Murtola, Tapio Visakorpi, Kirsi Talala, Teuvo Tammela, Aino Siltari, Stephane Lejeune, Laurence Colette, Simona Caputova, Delielena Poli, Sophie Byrne, Luz Fialho, Ashley Rowland, Neo Tapela, Nicola Di Flora, Kathi Apostolidis, Valerie Lemair, Bertrand De Meulder, Charles Auffray, Nesrine Taibi, Ayman Hijazy, Albert Saporta, Kai Sun, Shaun Power, Nazanin Zounemat Kermani, Kees van Bochove, Azadeh Tafreshiha, Chiara Bernini, Denis Horgan, Louise Fullwood, Marc Holtorf, Doron Lancet, Gabi Bernstein, Sheela Tripathee, Manfred Wirth, Michael Froehner, Beate Brenner, Angelika Borkowetz, Christian Thomas, Friedemann Horn, Kristin Reiche, Markus Kreuz, Andreas Josefsson, Delila Gasi Tandefelt, Jonas Hugosson, Jack Schalken, Henkjan Huisman, Thomas Hofmarcher, Peter Lindgren, Emelie Andersson, Adam Fridhammar, Monica Tames Grijalva, Susan Evans-Axelsson, Frank Verholen, Jihong Zong, John-Edward Butler-Ransohoff, Todd Williamson, Reg Waldeck, Amanda Bruno, Ekaterina Nevedomskaya, Samuel Fatoba, Niculae Constantinovici, Carl Steinbeisser, Monika Maass, Patrizia Torremante, Emmanuelle Dochy, Federica Pisa, Marc Dietrich Voss, Kishore Papineni, Jing Wang-silvanto, Robert Snijder, Xuewei Wang, Mark Lambrecht, Russ Wolfinger, Sherinne Eid, Soundarya Palanisamy, Samiul Haque, Laurent Antoni, Angela Servan, Katie Pascoe, Paul Robinson, Joana Lencart, Bertrand Jaton, Heidi Turunen, Olavi Kilkku, Pasi Pohjanjousi, Olli Voima, Liina Nevalaita, Keijo Punakivi, Sarah Seager, Shilpa Ratwani, Katarzyna Grzeslak, James Brash, Elaine Longden-Chapman, Danny Burke, Muriel Licour, Sarah Payne, Alan Yong, Flavia Lujan, Sophia Le Mare, Jan Hendrich, Michael Bussmann, Juckeland, Kotik, and Christian Reich
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Cancer survivorship ,Prostate cancer ,Quality of life ,Patient-reported outcome measures ,Diseases of the genitourinary system. Urology ,RC870-923 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures (PROMs). There have been recent advances in the availability of such PROMs. For instance, the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) is developing survivorship questionnaires. This provides an excellent first step in improving the data available on cancer survivorship. However, we propose that an agreed, standardised definition of (prostate) cancer survivorship must first be established. Only then can real-world data on survivorship be collected to strengthen our knowledge base. With more men than ever surviving PCa, this type of research is imperative to ensure that the quality of life of these men is considered as much as their quantity of life. Patient summary: As there are more prostate cancer survivors than ever before, research into cancer survivorship is crucial. We highlight the importance of such research and provide recommendations on how to carry it out. The first step should be establishing agreement on a standardised definition of survivorship. From this, patient-reported outcome measures can then be used to collect important survivorship data.
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- 2024
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4. Incidence of vestibular schwannoma in Finland, 1990–2017
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Aino Iivanainen, Jani Raitanen, and Anssi Auvinen
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Neuroma ,acoustic ,cranial nerve neoplasms ,incidence ,epidemiology ,Finland ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: An increasing trend in incidence of vestibular schwannomas (VS) has been reported, though not consistently, across populations. Materials and methods: We obtained data from the Finnish Cancer Registry on 1,149 VS cases diagnosed in 1990–2017 with tabular data up to 2022. We calculated age-standardised incidence rates (ASR) overall, by sex, and for 10-year age groups. We analysed time trends using Poisson and joinpoint regression. Results: The average ASR of VS in Finland during 1990–2017 was 8.6/1,000,000 person-years for women and 7.5/1,000,000 for men. A declining trend was found with an average annual percent change of −1.7% (95% confidence interval [CI]: −2.8%, −0.6%) for women, −2.2% (95% CI: −3.6%, −0.7%) for men, and −1.9% (95% CI: −2.9%, −1.0%) for both sexes combined. The ASR in women was 11.6/1,000,000 person-years in 1990 and it decreased to 8.2/1,000,000 by 2017. Correspondingly, the incidence in men was 7.1/1,000,000 in 1990 and decreased to 5.1/1,000,000 by 2017. Some decline in incidence over time was found in all age groups below 80 years, but the decline (2.3–3.1% per year) was statistically significant only in age groups 40–49, 50–59, and 60–69 years. In the oldest age group (80+ years), the incidence of VS increased by 16% per year. For 2018–2022, the ASR was 7.6/1,000,000 for both sexes combined, with a decline by −1.7% (95% CI: −2.3%, −1.2%) annually for the entire period 1990–2022. Conclusion: In contrast to the increasing incidence reported in some studies, we found a decreasing trend in VS incidence for both sexes in Finland.
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- 2024
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5. Mobile phone use and brain tumour risk – COSMOS, a prospective cohort study
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Maria Feychting, Joachim Schüz, Mireille B. Toledano, Roel Vermeulen, Anssi Auvinen, Aslak Harbo Poulsen, Isabelle Deltour, Rachel B. Smith, Joel Heller, Hans Kromhout, Anke Huss, Christoffer Johansen, Giorgio Tettamanti, and Paul Elliott
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Cell phones ,Radiofrequency fields ,Electromagnetic fields ,Non-ionizing radiation ,Brain neoplasms ,Cohort study ,Environmental sciences ,GE1-350 - Abstract
Background: Each new generation of mobile phone technology has triggered discussions about potential carcinogenicity from exposure to radiofrequency electromagnetic fields (RF-EMF). Available evidence has been insufficient to conclude about long-term and heavy mobile phone use, limited by differential recall and selection bias, or crude exposure assessment. The Cohort Study on Mobile Phones and Health (COSMOS) was specifically designed to overcome these shortcomings. Methods: We recruited participants in Denmark, Finland, the Netherlands, Sweden, and the UK 2007–2012. The baseline questionnaire assessed lifetime history of mobile phone use. Participants were followed through population-based cancer registers to identify glioma, meningioma, and acoustic neuroma cases during follow-up. Non-differential exposure misclassification was reduced by adjusting estimates of mobile phone call-time through regression calibration methods based on self-reported data and objective operator-recorded information at baseline. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma, meningioma, and acoustic neuroma in relation to lifetime history of mobile phone use were estimated with Cox regression models with attained age as the underlying time-scale, adjusted for country, sex, educational level, and marital status. Results: 264,574 participants accrued 1,836,479 person-years. During a median follow-up of 7.12 years, 149 glioma, 89 meningioma, and 29 incident cases of acoustic neuroma were diagnosed. The adjusted HR per 100 regression-calibrated cumulative hours of mobile phone call-time was 1.00 (95 % CI 0.98–1.02) for glioma, 1.01 (95 % CI 0.96–1.06) for meningioma, and 1.02 (95 % CI 0.99–1.06) for acoustic neuroma. For glioma, the HR for ≥ 1908 regression-calibrated cumulative hours (90th percentile cut-point) was 1.07 (95 % CI 0.62–1.86). Over 15 years of mobile phone use was not associated with an increased tumour risk; for glioma the HR was 0.97 (95 % CI 0.62–1.52). Conclusions: Our findings suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma.
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- 2024
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6. Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial
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Jaakko Nevalainen, Anssi Auvinen, Antti Rannikko, Teuvo Tammela, Kari Natunen, Jani Raitanen, and Tuomas Kilpeläinen
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Medicine - Abstract
Introduction Evidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis, and complications from biopsies and overtreatment. However, diagnostic accuracy studies have shown that detection of clinically insignificant prostate cancer can be reduced by MRI combined with targeted biopsies.The aim of the paper is to describe the analysis of the ProScreen randomised trial to assess the performance of the novel screening algorithm in terms of the primary outcome, prostate cancer mortality and secondary outcomes as intermediate indicators of screening benefits and harms of screening.Methods The trial aims to recruit at least 111 000 men to achieve sufficient statistical power for the primary outcome. Men will be allocated in a 1:3 ratio to the screening and control arms. Interim analysis is planned at 10 years of follow-up, and the final analysis at 15 years. Difference between the trial arms in prostate cancer mortality will be assessed by Gray’s test using intention-to-screen analysis of randomised men. Secondary outcomes will be the incidence of prostate cancer by disease aggressiveness, progression to advanced prostate cancer, death due to any cause and cost-effectiveness of screening.Ethics and dissemination The trial protocol was reviewed by the ethical committee of the Helsinki University Hospital (2910/2017). Results will be disseminated through publications in international peer-reviewed journals and at scientific meetings.Trial registration number NCT03423303
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- 2024
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7. Missingness in the expanded prostate cancer index short form (EPIC-26) – prevalence, patterns, and explanatory factors
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Anna-Maija Talvitie, Mika Helminen, Hanna Ojala, Teuvo Tammela, Anssi Auvinen, and Ilkka Pietilä
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The Expanded Prostate Cancer Index Composite Short Form ,Quality of life ,Prostate cancer ,Missing data ,Validity ,Patient-reported outcome measures ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background Researchers and clinicians using common clinical assessments need to attend to the prevalence of missing data to ensure the validity of the information gathered. The Expanded Prostate Cancer Index Short Form (EPIC-26) is a commonly used measurement scale used for assessing patients’ quality of life, but the measure lacks comprehensive analysis on missing data. We aimed to explore the quantity of missing answers in EPIC-26 and to characterize patterns and possible explanations of missing data in the survey. Methods The survey sample consisted of 625 Finnish prostate cancer patients who participated in a study with a 1-year follow-up with three measurement points (0, 6, and 12 months). Descriptive statistics were used to describe the study population and missingness level. A logistic regression was performed for each EPIC domain to study factors related to missingness during the follow-up. Results Proportions of missing answers in EPIC-26 were low (3.1–3.9%) between survey rounds. As much as 37% of patients left at least one question unanswered during their follow-up. The hormonal domain produced the most missing answers. Questions about breast tenderness/enlargement (question 13.b.), hot flashes (question 13.a.), frequency of erections (question 10.), and ability to reach orgasm (question 8.b.) were most frequently left unanswered. Higher age, lower education level, no relationship, more severe cancer, lower function scores in some EPIC domains, lower treatment satisfaction or self-rated health were associated with missingness. Conclusions Questions 13.b. and 13.a. might be considered female-specific symptoms, thus difficult to comprehend unless patients had already experienced side effects from androgen deprivation therapy. Questions 10. and 8.b. might be difficult to answer if the patient has been sexually inactive. To improve the measure’s validity, the questionnaire’s hormonal section requires additional explanation that the inquired symptoms are common treatment side effects of anti-androgen therapy; questions 8–10 require a not-applicable category for sexually inactive patients.
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- 2023
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8. Screening for prostate cancer: evidence, ongoing trials, policies and knowledge gaps
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Anssi Auvinen, Ola Bratt, Jonas Hugosson, Monique J Roobol, Hans Lilja, Rebecka Arnsrud Godtman, Mikael Hellström, and Jonas Wallström
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Long-term screening with serum prostate-specific antigen (PSA) and systematic prostate biopsies can reduce prostate cancer mortality but leads to unacceptable overdiagnosis. Over the past decade, diagnostic methods have improved and the indolent nature of low-grade prostate cancer has been established. These advances now enable more selective detection of potentially lethal prostate cancer. This non-systematic review summarises relevant diagnostic advances, previous and ongoing screening trials, healthcare policies and important remaining knowledge gaps.Evidence synthesis and conclusions: The strong association between low serum PSA values and minimal long-term risk of prostate cancer death allows for adjusting screening intervals. Use of risk calculators, biomarkers and MRI to select men with a raised PSA value for biopsy and lesion-targeting rather than systematic prostate biopsies reduce the detection of low-grade cancer and thereby overdiagnosis. These improvements recently led the European Union to recommend its member states to evaluate the feasibility and effectiveness of organised screening programmes for prostate cancer. Nonetheless, important knowledge gaps remain such as the performance of modern diagnostic methods in long-term screening programmes and their impact on mortality. The knowledge gaps are currently being addressed in three large randomised screening trials. Population-based pilot programmes will contribute critical practical experience.
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- 2023
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9. Clustering of pediatric onset inflammatory bowel disease in Finland: a nationwide register-based study
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Atte Nikkilä, Anssi Auvinen, and Kaija-Leena Kolho
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Cluster analysis ,Crohn’s disease ,Environment ,Epidemiology ,Ulcerative colitis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data. Methods We included all PIBD cases diagnosed at ages
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- 2022
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10. Incidence trends of childhood central nervous system tumors in Finland 1990–2017
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Jad Abuhamed, Atte Nikkilä, Jani Raitanen, Wafa Alimam, Olli Lohi, Janne Pitkäniemi, Hannu Haapasalo, and Anssi Auvinen
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Incidence ,CNS tumors ,Childhood cancer ,Trends ,Cancer register ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Introduction Central nervous system (CNS) tumors are a leading cause of cancer-related morbidity and mortality in children. Our aim is to characterize incidence trends of pediatric CNS tumors in Finland over the last three decades. Methods Data on all benign and malignant incident CNS tumors diagnosed in children aged 0–14 years in 1990–2017 were extracted from the Finnish Cancer Registry and classified according to the 2016 WHO classification of CNS tumors. We analyzed age-standardized incidence rates (ASR) for pediatric CNS tumors overall and by sex, age, tumor histology, grade, and location using Poisson regression. We used joinpoint regression to evaluate changes in trends. Results Overall, 1117 pediatric CNS tumor cases were registered in Finland with a 1.2:1 male to female ratio. The average annual ASR was 4.3 per 100,000 person-years (95% CI 4.26, 4.34). The most common tumor type was pilocytic astrocytoma (30% of tumors), followed by medulloblastoma (10%) with incidence rates of 1.30 and 0.45 per 100,000 person-years, respectively. The overall incidence of pediatric CNS tumors increased by an annual percentage change (APC) of 0.8% (95% CI 0.2, 1.4). We observed no major changes in incidence trends of tumor histology groups or tumor location groups. The ASR of benign tumors increased by an APC of 1.0 (95% CI 0.1, 2.0). Conclusions Utilizing the high-quality and completeness of data in the Finnish Cancer registry, we found that the incidence of pediatric CNS tumors in Finland has increased slightly from 1990 until 2017. Although variations in diagnostic and registration practices over time might have affected the rates, the trend may also reflect a true increase in incidence.
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- 2022
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11. Intervention-related Deaths in the European Randomized Study of Screening for Prostate Cancer
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Rebecka Arnsrud Godtman, Sebastiaan Remmers, Gunnar Aus, Vera Nelen, Liesbet van Eycken, Arnauld Villers, Xavier Rebillard, Maciej Kwiatkowski, Stephen Wyler, Donella Puliti, Giuseppe Gorini, Alvaro Paez, Marcos Lujan, Teuvo Tammela, Chris Bangma, Anssi Auvinen, and Monique J. Roobol
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Cause of death ,Complications ,Prostate cancer ,Prostate-specific antigen ,Screening ,Treatment ,Diseases of the genitourinary system. Urology ,RC870-923 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. Objective: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). Design, setting, and participants: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55–69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. Outcome measurements and statistical analysis: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. Results and limitations: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99–1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. Conclusions: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. Patient summary: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.
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- 2021
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12. Cancer screening simulation models: a state of the art review
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Aleksandr Bespalov, Anton Barchuk, Anssi Auvinen, and Jaakko Nevalainen
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Cancer screening ,Modelling ,Systematic review ,Microsimulation ,Trends ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Background Nowadays, various simulation approaches for evaluation and decision making in cancer screening can be found in the literature. This paper presents an overview of approaches used to assess screening programs for breast, lung, colorectal, prostate, and cervical cancers. Our main objectives are to describe methodological approaches and trends for different cancer sites and study populations, and to evaluate quality of cancer screening simulation studies. Methods A systematic literature search was performed in Medline, Web of Science, and Scopus databases. The search time frame was limited to 1999–2018 and 7101 studies were found. Of them, 621 studies met inclusion criteria, and 587 full-texts were retrieved, with 300 of the studies chosen for analysis. Finally, 263 full texts were used in the analysis (37 were excluded during the analysis). A descriptive and trend analysis of models was performed using a checklist created for the study. Results Currently, the most common methodological approaches in modeling cancer screening were individual-level Markov models (34% of the publications) and cohort-level Markov models (41%). The most commonly evaluated cancer types were breast (25%) and colorectal (24%) cancer. Studies on cervical cancer evaluated screening and vaccination (18%) or screening only (13%). Most studies have been conducted for North American (42%) and European (39%) populations. The number of studies with high quality scores increased over time. Conclusions Our findings suggest that future directions for cancer screening modelling include individual-level Markov models complemented by screening trial data, and further effort in model validation and data openness.
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- 2021
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13. Time trends in mobile phone use and glioma incidence among males in the Nordic Countries, 1979–2016
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Isabelle Deltour, Aslak Harbo Poulsen, Christoffer Johansen, Maria Feychting, Tom Børge Johannesen, Anssi Auvinen, and Joachim Schüz
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Glioma ,Mobile phones ,Cancer registry ,Modelling ,Environmental sciences ,GE1-350 - Abstract
Introduction: In the Nordic countries, the use of mobile phones increased sharply in the mid-1990s especially among middle-aged men. We investigated time trends in glioma incidence rates (IR) with the perspective to inform about the plausibility of brain tumour risks from mobile phone use reported in some case-control studies. Methods: We analysed IR of glioma in Denmark, Finland, Norway, and Sweden among men aged 40–69 years, using data from national cancer registries and population statistics during 1979–2016, using log-linear joinpoint analysis. Information on regular mobile phone use and amount of call-time was obtained from major studies of mobile phones in these countries. We compared annual observed incidence with that expected under various risk scenarios to assess which of the reported effect sizes are compatible with the observed IR. The expected numbers of cases were computed accounting for an impact of other factors besides mobile phone use, such as improved cancer registration. Results: Based on 18,232 glioma cases, IR increased slightly but steadily with a change of 0.1% (95 %CI 0.0%; 0.3%) per year during 1979–2016 among 40–59-year-old men and for ages 60–69, by 0.6 % (95 %CI 0.4; 0.9) annually. The observed IR trends among men aged 40–59 years were incompatible with risk ratios (RR) 1.08 or higher with a 10-year lag, RR ≥ 1.2 with 15-year lag and RR ≥ 1.5 with 20-year lag. For the age group 60–69 years, corresponding effect sizes RR ≥ 1.4, ≥2 and ≥ 2.5 could be rejected for lag times 10, 15 and 20 years. Discussion: This study confirms and reinforces the conclusions that no changes in glioma incidence in the Nordic countries have occurred that are consistent with a substantial risk attributable to mobile phone use. This particularly applies to virtually all reported risk increases reported by previous case-control studies with positive findings.
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- 2022
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14. Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine
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Juho Jasu, Teemu Tolonen, Emmanuel S. Antonarakis, Himisha Beltran, Susan Halabi, Mario A. Eisenberger, Michael A. Carducci, Yohann Loriot, Kim Van der Eecken, Martijn Lolkema, Charles J. Ryan, Sinja Taavitsainen, Silke Gillessen, Gunilla Högnäs, Timo Talvitie, Robert J. Taylor, Antti Koskenalho, Piet Ost, Teemu J. Murtola, Irina Rinta-Kiikka, Teuvo Tammela, Anssi Auvinen, Paula Kujala, Thomas J. Smith, Pirkko-Liisa Kellokumpu-Lehtinen, William B. Isaacs, Matti Nykter, Juha Kesseli, and G. Steven Bova
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Phenotyping ,Prostate cancer ,Metastasis ,Autopsy ,Electronic medical records ,Complications ,Diseases of the genitourinary system. Urology ,RC870-923 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. Objective: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials. Design, setting, and participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature. Intervention: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. Outcome measurements and statistical analysis: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression. Results and limitations: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of “skeletal-related events” complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index
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- 2021
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15. Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study
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Ronja Hietikko, Tuomas P. Kilpeläinen, Anu Kenttämies, Johanna Ronkainen, Kirsty Ijäs, Kati Lind, Suvi Marjasuo, Juha Oksala, Outi Oksanen, Tuomas Saarinen, Ritja Savolainen, Kimmo Taari, Teuvo L. J. Tammela, Tuomas Mirtti, Kari Natunen, Anssi Auvinen, and Antti Rannikko
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Prostate cancer ,Agreement ,Magnetic resonance imaging ,PI-RADS version 2 ,Screening ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods From January 2014 to January 2018, 100 men aged 50–63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss’ kappa (κ) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD ±10%, range 62–96%), and mean specificity 60% (SD ±22%, range 27–82%). For csPCa (Gleason Grade 2–5) MRI was equally sensitive (mean 82%, SD ±9%, range 67–97%) but less specific (mean 47%, SD ±20%, range 21–75%). Interreader agreement for any lesion was fair (κ 0.40) and for PI-RADS 4–5 lesions it was moderate (κ 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.
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- 2020
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16. Long‐term health‐related quality of life among men with prostate cancer in the Finnish randomized study of screening for prostate cancer
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Kirsi Talala, Sirpa Heinävaara, Kimmo Taari, Teuvo L. J. Tammela, Paula Kujala, Ulf‐Håkan Stenman, Nea Malila, and Anssi Auvinen
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prostate cancer ,quality of life ,screening ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The long‐term health‐related quality of life (HRQOL) impacts of PCa screening have not been adequately evaluated. We aimed to compare the generic and disease‐specific health‐related quality of life (HRQOL) among men with prostate cancer in the screening arm with the control arm of the PSA‐based prostate cancer screening trial in up to 15 years of follow‐up. Materials and methods This study was conducted within population‐based Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). During 1996‐1999 80,458 men were randomized to the serum prostate‐specific antigen (PSA) screening arm (SA, N = 32 000) and the control arm (CA, N = 48 458). Men in the screening arm were screened at 4‐year intervals until 2007. HRQOL questionnaires were delivered to newly diagnosed prostate cancer patients in the screening and control arm 1996‐2006 (N = 5128) at the time of diagnosis (baseline), at 3‐month, 12‐month and 5, 10, and 15‐year follow‐up. Validated UCLA Prostate Cancer Index (UCLA‐PCI) and RAND 36‐Item Health Survey were used for HRQOL assessment. The data were analyzed with a random effects model for repeated measures. Results At baseline, men with prostate cancer in the screening arm reported better Sexual Function, as well as less Sexual and Urinary Bother. Long‐term follow‐up revealed slightly higher HRQOL scores in the screening arm in prostate cancer specific measures at 10‐year post diagnosis, but the differences were statistically significant only in Urinary Bother (UCLA‐PCI score 77.9; 95% CI 75.2 to 80.5 vs. 70.9; 95% CI 66.8 to 74.9 P = .005). The generic HRQOL scores were comparable between the trial arms. The overall differences in disease‐specific or generic HRQOL scores by trial arm did not vary during the follow‐up. Conclusion No major differences were observed in HRQOL in men with prostate cancer between the prostate cancer screening and control arms during five to 15‐year follow‐up.
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- 2020
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17. Predicting residential radon concentrations in Finland: Model development, validation, and application to childhood leukemia
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Atte Nikkilä, Hannu Arvela, Juha Mehtonen, Jani Raitanen, Merja Heinäniemi, Olli Lohi, and Anssi Auvinen
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carcinogen ,leukemia ,radon ,finland ,radon concentration ,childhood leukemia ,indoor radon ,epidemiology ,etiology ,cancer ,Public aspects of medicine ,RA1-1270 - Abstract
OBJECTIVES: Inhaled radon gas is a known alpha-emitting carcinogen linked especially to lung cancer. Studies on higher concentrations of indoor radon and childhood leukemia have conflicting but largely negative results. In this study, we aimed to create a sophisticated statistical model to predict indoor radon concentrations and apply it to a Finnish childhood leukemia case–control dataset. METHODS: Prediction was based on ~80 000 indoor radon measurements, which were linked to national registries for potential indoor radon predictors based on the literature. In modelling, we used classical methods, random forests and deep neural networks. We had 1093 cases and 3279 controls from a nationwide case–control study. We estimated odds ratio (OR) for childhood leukemia using conditional logistic regression adjusted for potential confounders. RESULTS: The r^2 of the final log-linear model was 0.21 for houses and 0.20 for apartments. Using random forest method, we were able to obtain slightly better fit for both houses (r^2 = 0.28) and apartments (r^2 = 0.23). In a risk analysis based on the case–control data with log-linear model, we observed a non-significant (P=0.54) increase with predicted radon concentrations [OR for the 2^nd quartile 1.08, 95% confidence interval (CI) 0.77–1.50, OR 1.10 with 95% CI 0.79–1.53 for the 3^rd, and 1.29 with 95% CI 0.93–1.77 for the highest quartile]. CONCLUSIONS: Our modelling and the previously published models performed similarly but involves major uncertainties, and the results should be interpreted with caution. We observed a slight non-significant increase in risk of childhood leukemia related to higher average indoor radon concentrations.
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- 2020
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18. Exposure to loud noise and risk of vestibular schwannoma: results from the INTERPHONE international case‒control study
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Isabelle Deltour, Brigitte Schlehofer, Amélie Massardier-Pilonchéry, Klaus Schlaefer, Bruce Armstrong, Graham G Giles, Jack Siemiatycki, Marie-Elise Parent, Daniel Krewski, Mary McBride, Christoffer Johansen, Anssi Auvinen, Tiina Salminen, Martine Hours, Lucile Montestrucq, Maria Blettner, Gabriele Berg-Beckhoff, Siegal Sadetzki, Angela Chetrit, Susanna Lagorio, Ivano Iavarone, Naohito Yamaguchi, Toru Takebayashi, Alistair Woodward, Angus Cook, Tore Tynes, Lars Klaeboe, Maria Feychting, Stefan Lönn, Sarah Fleming, Anthony J Swerdlow, Minouk J Schoemaker, Monika Moissonnier, Ausrele Kesminiene, Elisabeth Cardis, Joachim Schüz, and INTERPHONE Study Group
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vestibular schwannoma ,interphone ,case‒control study ,acoustic neuroma ,epidemiology ,exposure ,noise ,noise exposure ,international ,loud noise ,Public aspects of medicine ,RA1-1270 - Abstract
OBJECTIVE: Studies of loud noise exposure and vestibular schwannomas (VS) have shown conflicting results. The population-based INTERPHONE case‒control study was conducted in 13 countries during 2000–2004. In this paper, we report the results of analyses on the association between VS and self-reported loud noise exposure. METHODS: Self-reported noise exposure was analyzed in 1024 VS cases and 1984 matched controls. Life-long noise exposure was estimated through detailed questions. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using adjusted conditional logistic regression for matched sets. RESULTS: The OR for total work and leisure noise exposure was 1.6 (95% CI 1.4–1.9). OR were 1.5 (95% CI 1.3–1.9) for only occupational noise, 1.9 (95% CI 1.4–2.6) for only leisure noise and 1.7 (95% CI 1.2–2.2) for exposure in both contexts. OR increased slightly with increasing lag-time. For occupational exposures, duration, time since exposure start and a metric combining lifetime duration and weekly exposure showed significant trends of increasing risk with increasing exposure. OR did not differ markedly by source or other characteristics of noise. CONCLUSION: The consistent associations seen are likely to reflect either recall bias or a causal association, or potentially indicate a mixture of both.
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- 2019
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19. Inverse Association between Statin Use and Cancer Mortality Relates to Cholesterol Level
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Antti I. Peltomaa, Kirsi Talala, Kimmo Taari, Teuvo L. J. Tammela, Anssi Auvinen, and Teemu J. Murtola
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statins ,cancer ,cholesterol ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Statins have been associated with a decreased cancer mortality. However, cholesterol level as such may modify the risk of cancer death. To clarify the complex interplay between statins, cholesterol level, and cancer mortality, we conducted a comprehensive analysis to separate the effects of cholesterol level and statin medication on cancer mortality. Our study population consisted of 16,924 men participating in the Finnish Randomized Study of Screening for Prostate Cancer with at least one cholesterol measurement during follow-up (1996–2017). Cox proportional regression was used to estimate hazard ratios. In total, 1699 cancer deaths were observed during the median follow-up of 19 years. When statins’ association with the risk of cancer death was estimated without adjustment for cholesterol level, statin use was associated with a lowered cancer mortality (HR 0.87; 95% CI 0.79–0.97) compared to non-users. However, with further adjustment for total cholesterol level, statin use was no longer associated with a lower cancer mortality (HR 1.08; 95% CI 0.97–1.20). Upon stratified analysis, statin use was associated with a decreased cancer mortality only if the total cholesterol level decreased after the initiation of statin use (HR 0.66; 95% CI 0.58–0.76). The inverse association between statin use and cancer mortality is limited to men with a reduction in total cholesterol level after the commencement of statins, i.e., statin use is associated with a lowered cancer mortality only if the total cholesterol level decreases. This suggests that the effect of statin use on cancer mortality relates to the decreased total cholesterol level.
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- 2022
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20. Long-term effect of mobile phone use on sleep quality: Results from the cohort study of mobile phone use and health (COSMOS)
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Giorgio Tettamanti, Anssi Auvinen, Torbjörn Åkerstedt, Katja Kojo, Anders Ahlbom, Sirpa Heinävaara, Paul Elliott, Joachim Schüz, Isabelle Deltour, Hans Kromhout, Mireille B. Toledano, Aslak Harbo Poulsen, Christoffer Johansen, Roel Vermeulen, Maria Feychting, and Lena Hillert
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Cohort study ,Cell phone ,Sleep disturbance ,Insomnia ,Electromagnetic fields ,Environmental sciences ,GE1-350 - Abstract
Background: Effects of radiofrequency electromagnetic field exposure (RF-EMF) from mobile phone use on sleep quality has mainly been investigated in cross-sectional studies. The few previous prospective cohort studies found no or inconsistent associations, but had limited statistical power and short follow-up. In this large prospective cohort study, our aim was to estimate the effect of RF-EMF from mobile phone use on different sleep outcomes. Materials and methods: The study included Swedish (n = 21,049) and Finnish (n = 3120) participants enrolled in the Cohort Study of Mobile Phone Use and Health (COSMOS) with information about operator-recorded mobile phone use at baseline and sleep outcomes both at baseline and at the 4-year follow-up. Sleep disturbance, sleep adequacy, daytime somnolence, sleep latency, and insomnia were assessed using the Medical Outcome Study (MOS) sleep questionnaire. Results: Operator-recorded mobile phone use at baseline was not associated with most of the sleep outcomes. For insomnia, an odds ratio (OR) of 1.24, 95% CI 1.03–1.51 was observed in the highest decile of mobile phone call-time (>258 min/week). With weights assigned to call-time to account for the lower RF-EMF exposure from Universal Mobile Telecommunications Service (UMTS, 3G) than from Global System for Mobile Communications (GSM, 2G) the OR was 1.09 (95% CI 0.89–1.33) in the highest call-time decile. Conclusion: Insomnia was slightly more common among mobile phone users in the highest call-time category, but adjustment for the considerably lower RF-EMF exposure from the UMTS than the GSM network suggests that this association is likely due to other factors associated with mobile phone use than RF-EMF. No association was observed for other sleep outcomes. In conclusion, findings from this study do not support the hypothesis that RF-EMF from mobile phone use has long-term effects on sleep quality.
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- 2020
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21. Radiation exposure from computerized tomography and risk of childhood leukemia: Finnish register-based case-control study of childhood leukemia (FRECCLE)
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Atte Nikkilä, Jani Raitanen, Olli Lohi, and Anssi Auvinen
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
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22. Trends of computed tomography use among children in Finland
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Jad Abuhamed, Atte Nikkilä, Olli Lohi, and Anssi Auvinen
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Computed tomography ,Pediatric ,Radiation protection ,Dosimetry ,Imaging ,Brain ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Objectives: CT is an essential diagnostic tool in health care. However, CT delivers relatively high levels of radiation which has been associated with an increased risk of childhood cancer. To address this, we evaluated patterns and time trends of CT use among children in Finland during the period in which changes in pediatric CT imaging practices were reported in several countries. Methods: Data on CTs performed on children younger than 15 years were obtained from Finland’s largest eight hospitals. CT data included the period 1996–2010 with an estimated coverage of more than 80 % of pediatric CT imaging in Finland. Joinpoint regression was used for trends analysis. CT radiation doses were estimated based on a Finnish dosimetry survey. Results: A total of 48,807 pediatric CTs were performed in 1996–2010. More boys (55.5 %) were scanned than girls (42.8 %). CT numbers increased up to 2002, then decreased significantly (-6.9 % per year, 95 % CI: -10.4 to -3.2) towards 2005 and to a lesser extent thereafter, particularly among younger children. All CT types decreased in recent years, except for chest, spine, and extremities. The frequency of head CTs related to the diagnoses of intracranial injury, migraine and headache decreased towards the end of the study period. The estimated annual average effective dose from the three most common CT examinations was 0.004 mSv per child in the population. Conclusions: The frequency of pediatric CTs in Finland started to decrease after 2002. Apart from chest and orthopedic CTs, the utilization of pediatric CT imaging declined in recent years, most likely explained by improved awareness of medical radiation risks and reliance on alternative modalities such as MRI and ultrasound.
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- 2020
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23. Antihypertensive drug use and prostate cancer-specific mortality in Finnish men.
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Aino Siltari, Teemu J Murtola, Kirsi Talala, Kimmo Taari, Teuvo L J Tammela, and Anssi Auvinen
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Medicine ,Science - Abstract
The aim of this study was to investigate pre- and post-diagnostic use of antihypertensive drugs on prostate cancer (PCa)-specific survival and the initiation of androgen deprivation therapy (ADT). The cohort investigated 8,253 PCa patients with 837 PCa-specific deaths during the median follow-up of 7.6 years after diagnosis. Information on drug use, cancer incidence, clinical features of PCa, and causes of death was collected from Finnish registries. Hazard ratios with 95% confidence intervals were calculated using Cox regression with antihypertensive drug use as a time-dependent variable. Separate analyses were performed on PCa survival related to pre- and post-diagnostic use of drugs and on the initiation of ADT. Antihypertensive drug use overall was associated with an increased risk of PCa-specific death (Pre-PCa: 1.21 (1.04-1.4), Post-PCa: 1.2 (1.02-1.41)). With respect to the separate drug groups, angiotensin II type 1 receptor (ATr) blockers, were associated with improved survival (Post-PCa: 0.81 (0.67-0.99)) and diuretics with an increased risk (Post-PCa: 1.25 (1.05-1.49)). The risk of ADT initiation was slightly higher among antihypertensive drug users as compared to non-users. In conclusion, this study supports anti-cancer effect of ATr blockers on PCa prognosis and this should be investigated further in controlled clinical trials.
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- 2020
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24. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
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Tokhir Dadaev, Edward J. Saunders, Paul J. Newcombe, Ezequiel Anokian, Daniel A. Leongamornlert, Mark N. Brook, Clara Cieza-Borrella, Martina Mijuskovic, Sarah Wakerell, Ali Amin Al Olama, Fredrick R. Schumacher, Sonja I. Berndt, Sara Benlloch, Mahbubl Ahmed, Chee Goh, Xin Sheng, Zhuo Zhang, Kenneth Muir, Koveela Govindasami, Artitaya Lophatananon, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Catherine M. Tangen, Phyllis Goodman, Ian M. Thompson, Jyotsna Batra, Suzanne Chambers, Leire Moya, Judith Clements, Lisa Horvath, Wayne Tilley, Gail Risbridger, Henrik Gronberg, Markus Aly, Tobias Nordström, Paul Pharoah, Nora Pashayan, Johanna Schleutker, Teuvo L. J. Tammela, Csilla Sipeky, Anssi Auvinen, Demetrius Albanes, Stephanie Weinstein, Alicja Wolk, Niclas Hakansson, Catharine West, Alison M. Dunning, Neil Burnet, Lorelei Mucci, Edward Giovannucci, Gerald Andriole, Olivier Cussenot, Géraldine Cancel-Tassin, Stella Koutros, Laura E. Beane Freeman, Karina Dalsgaard Sorensen, Torben Falck Orntoft, Michael Borre, Lovise Maehle, Eli Marie Grindedal, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Ruth C. Travis, Tim J. Key, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Sue Ann Ingles, Mariana C. Stern, Barry Rosenstein, Sarah Kerns, Harry Ostrer, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Xin Guo, Guomin Wang, Zan Sun, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Liesel M. FitzGerald, Adam S. Kibel, Bettina F. Drake, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Robert Szulkin, Martin Eklund, Manolis Kogevinas, Javier Llorca, Gemma Castaño-Vinyals, Kathryn L. Penney, Meir Stampfer, Jong Y. Park, Thomas A. Sellers, Hui-Yi Lin, Janet L. Stanford, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Elaine A. Ostrander, Milan S. Geybels, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weisher, Rasmus Bisbjerg, Martin Andreas Røder, Peter Iversen, Hermann Brenner, Katarina Cuk, Bernd Holleczek, Christiane Maier, Manuel Luedeke, Thomas Schnoeller, Jeri Kim, Christopher J. Logothetis, Esther M. John, Manuel R. Teixeira, Paula Paulo, Marta Cardoso, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, Kim De Ruyck, Gert De Meerleer, Piet Ost, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Daniel W. Lin, Lisa F. Newcomb, Davor Lessel, Marija Gamulin, Tomislav Kulis, Radka Kaneva, Nawaid Usmani, Chavdar Slavov, Vanio Mitev, Matthew Parliament, Sandeep Singhal, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Monique J. Roobol, Guido Jenster, Ron H. N. van Schaik, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Jianfeng Xu, Kay-Tee Khaw, Lisa Cannon-Albright, Hardev Pandha, Agnieszka Michael, Andrzej Kierzek, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Sara Lindstrom, Constance Turman, Jing Ma, David J. Hunter, Elio Riboli, Afshan Siddiq, Federico Canzian, Laurence N. Kolonel, Loic Le Marchand, Robert N. Hoover, Mitchell J. Machiela, Peter Kraft, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Matthew Freedman, Fredrik Wiklund, Stephen Chanock, Brian E. Henderson, Douglas F. Easton, Christopher A. Haiman, Rosalind A. Eeles, David V. Conti, and Zsofia Kote-Jarai
- Subjects
Science - Abstract
Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.
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- 2018
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25. Are There Limits in Explainability of Prognostic Biomarkers? Scrutinizing Biological Utility of Established Signatures
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Frank Emmert-Streib, Kalifa Manjang, Matthias Dehmer, Olli Yli-Harja, and Anssi Auvinen
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prognostic biomarker ,causal model ,computational biology ,biostatistics ,genomics ,survival analysis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Prognostic biomarkers can have an important role in the clinical practice because they allow stratification of patients in terms of predicting the outcome of a disorder. Obstacles for developing such markers include lack of robustness when using different data sets and limited concordance among similar signatures. In this paper, we highlight a new problem that relates to the biological meaning of already established prognostic gene expression signatures. Specifically, it is commonly assumed that prognostic markers provide sensible biological information and molecular explanations about the underlying disorder. However, recent studies on prognostic biomarkers investigating 80 established signatures of breast and prostate cancer demonstrated that this is not the case. We will show that this surprising result is related to the distinction between causal models and predictive models and the obfuscating usage of these models in the biomedical literature. Furthermore, we suggest a falsification procedure for studies aiming to establish a prognostic signature to safeguard against false expectations with respect to biological utility.
- Published
- 2021
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26. Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer
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Pete T. T. Kinnunen, Teemu J. Murtola, Kirsi Talala, Kimmo Taari, Teuvo L. J. Tammela, and Anssi Auvinen
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Prostate cancer ,Warfarin ,Anticoagulant ,Survival ,Cohort ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. Methods The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. Results In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. Conclusions We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.
- Published
- 2017
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27. Cost-effectiveness analysis of PSA-based mass screening: Evidence from a randomised controlled trial combined with register data.
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Neill Booth, Pekka Rissanen, Teuvo L J Tammela, Paula Kujala, Ulf-Håkan Stenman, Kimmo Taari, Kirsi Talala, and Anssi Auvinen
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Medicine ,Science - Abstract
In contrast to earlier studies which have used modelling to perform cost-effectiveness analysis, this study links data from a randomised controlled trial with register data from nationwide registries to reveal new evidence on costs, effectiveness, and cost-effectiveness of organised mass prostate-cancer screening based on prostate-specific antigen (PSA) testing. Cost-effectiveness analyses were conducted with individual-level data on health-care costs from comprehensive registers and register data on real-world effectiveness from the two arms of the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC), following 80,149 men from 1996 through 2015. The study examines cost-effectiveness in terms of overall mortality and, in addition, in terms of diagnosed men's mortality from prostate cancer and mortality with but not from prostate cancer. Neither arm of the FinRSPC was clearly more cost-effective in analysis in terms of overall mortality. Organised screening in the FinRSPC could be considered cost-effective in terms of deaths from prostate cancer: averting just over one death per 1000 men screened. However, even with an estimated incremental cost-effectiveness ratio of below 20,000€ per death avoided, this result should not be considered in isolation. This is because mass screening in this trial also resulted in increases in death with, but not from, prostate cancer: with over five additional deaths per 1000 men screened. Analysis of real-world data from the FinRSPC reveals new evidence of the comparative effectiveness of PSA-based screening after 20 years of follow-up, suggesting the possibility of higher mortality, as well as higher healthcare costs, for screening-arm men who have been diagnosed with prostate cancer but who do not die from it. These findings should be corroborated or contradicted by similar analyses using data from other trials, in order to reveal if more diagnosed men have also died in the screening arms of other trials of mass screening for prostate cancer.
- Published
- 2019
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28. Radiation exposure from computerized tomography and risk of childhood leukemia: Finnish register-based case-control study of childhood leukemia (FRECCLE)
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Atte Nikkilä, Jani Raitanen, Olli Lohi, and Anssi Auvinen
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The only well-established risk factors for childhood leukemia are high-dose ionizing radiation and Down syndrome. Computerized tomography is a common source of low-dose radiation. In this study, we examined the magnitude of the risk of childhood leukemia after pediatric computed tomography examinations. We evaluated the association of computed tomography scans with risk of childhood leukemia in a nationwide register-based case-control study. Cases (n=1,093) were identified from the population-based Finnish Cancer Registry and three controls, matched by gender and age, were randomly selected for each case from the Population Registry. Information was also obtained on birth weight, maternal smoking, parental socioeconomic status and background gamma radiation. Data on computed tomography scans were collected from the ten largest hospitals in Finland, covering approximately 87% of all pediatric computed tomography scans. Red bone marrow doses were estimated with NCICT dose calculation software. The data were analyzed using exact conditional logistic regression analysis. A total of 15 cases (1.4%) and ten controls (0.3%) had undergone one or more computed tomography scans, excluding a 2-year latency period. For one or more computed tomography scans, we observed an odds ratio of 2.82 (95% confidence interval: 1.05 – 7.56). Cumulative red bone marrow dose from computed tomography scans showed an excess odds ratio of 0.13 (95% confidence interval: 0.02 – 0.26) per mGy. Our results are consistent with the notion that even low doses of ionizing radiation observably increase the risk of childhood leukemia. However, the observed risk estimates are somewhat higher than those in earlier studies, probably due to random error, although unknown predisposing factors cannot be ruled out.
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- 2018
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29. Pharmacoepidemiological Evaluation in Prostate Cancer—Common Pitfalls and How to Avoid Them
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Aino Siltari, Anssi Auvinen, and Teemu J. Murtola
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pharmacoepidemiology ,prostate cancer ,metabolism ,common biases ,confounding ,retrospective studies ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Pharmacoepidemiologic research provides opportunities to evaluate how commonly used drug groups, such as cholesterol-lowering or antidiabetic drugs, may affect the prostate cancer risk or mortality. This type of research is valuable in estimating real-life drug effects. Nonetheless, pharmacoepidemiological studies are prone to multiple sources of bias that mainly arise from systematic differences between medication users and non-users. If these are not appreciated and properly controlled for, there is a risk of obtaining biased results and reaching erroneous conclusions. Therefore, in order to improve the quality of future research, we describe common biases in pharmacoepidemiological studies, particularly in the context of prostate cancer research. We also list common ways to mitigate these biases and to estimate causality between medication use and cancer outcomes.
- Published
- 2021
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30. Prognostic Index for Predicting Prostate Cancer Survival in a Randomized Screening Trial: Development and Validation
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Subas Neupane, Jaakko Nevalainen, Jani Raitanen, Kirsi Talala, Paula Kujala, Kimmo Taari, Teuvo L. J. Tammela, Ewout W. Steyerberg, and Anssi Auvinen
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prognostic index ,prediction model ,prostate cancer ,mortality ,screening trial ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up was divided into three periods (0–3, 3–9 and 9–20 years) for development and two corresponding validation periods (3–6 and 9–15 years). A multivariable complementary log–log regression model was used to calculate the full prognostic index. Predicted cause-specific survival at 10 years from diagnosis was calculated for the control arm using a simplified risk score at diagnosis. The full prognostic index discriminates well men with PCa with different survival. The area under the curve (AUC) was 0.83 for both the 3–6 year and 9–15 year validation periods. In the simplified risk score, patients with a low risk score at diagnosis had the most favorable survival, while the outcome was poorest for the patients with high risk scores. The prognostic index was able to distinguish well between men with higher and lower survival, and the simplified risk score can be used as a basis for decision making.
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- 2021
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31. Diabetes and Breast Cancer Subtypes.
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Heleen K Bronsveld, Vibeke Jensen, Pernille Vahl, Marie L De Bruin, Sten Cornelissen, Joyce Sanders, Anssi Auvinen, Jari Haukka, Morten Andersen, Peter Vestergaard, and Marjanka K Schmidt
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Medicine ,Science - Abstract
Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes.This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (≤50 and >50 years), women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories) to women without diabetes, to select ~300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR), HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211) and women without diabetes (n = 101), irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%CI:1.07-5.55)), HER2-negative (OR = 2.84(95%CI:1.11-7.22)), and basal-like (OR = 3.14(95%CI:1.03-9.60) tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95%CI:0.95-6.45)) and triple negative (OR = 2.60(95%CI:0.88-7.67) tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general.We found no compelling evidence that women with diabetes, treated with or without insulin, develop different breast cancer subtypes than women without diabetes. However, premenopausal women with diabetes tended to develop breast tumors that do not express hormonal receptors, which are typically associated with poor prognosis.
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- 2017
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32. Non-Steroidal Anti-Inflammatory Drugs and Cancer Death in the Finnish Prostate Cancer Screening Trial.
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Thea Veitonmäki, Teemu J Murtola, Kirsi Talala, Kimmo Taari, Teuvo Tammela, and Anssi Auvinen
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Medicine ,Science - Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91-2.15) compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40-2.99, HR 1.91, 95% CI 1.57-2.32 and HR 1.93, 95% CI 1.58-2.37, respectively). The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05-1.18). When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65-0.73). Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70-0.82). Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded.
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- 2016
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33. Lens opacities among physicians occupationally exposed to ionizing radiation – a pilot study in Finland
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Samy Mrena, Tero Kivelä, Päivi Kurttio, and Anssi Auvinen
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ionizing radiation ,physician ,radiation effect ,lens opacity ,radiation protection ,cataract ,lens ,exposure ,occupational ,crystalline ,pilot study ,radiology ,finland ,Public aspects of medicine ,RA1-1270 - Abstract
OBJECTIVES: The aim of this study was to estimate the prevalence of lens opacities among physicians occupationally exposed to radiation – overall and by occupational factors – and to assess the feasibility of a large-scale study for risk assessment. METHODS: Based on a nationwide registry of 1312 physicians, mostly radiologists with occupational exposure to ionizing radiation, 120 subjects were invited to participate, of which 59 (49%) consented. The inclusion criteria included (i) age 45–70 years, (ii) cumulative recorded radiation dose >10 mSv, and (iii) duration of work with dose monitoring >15 years. The participants completed a questionnaire regarding occupational history and other risk factors for lens opacities. A full ophthalmological examination was performed. Lenticular changes were graded using the Lens Opacities Classification System, version II (LOCS II), and the Nidek EAS–1000 Scheimpflug slit-imaging videophotography system. RESULTS: Lens opacities were detected in 42% [95% confidence interval (95% CI) 29–55] of the 57 physicians without prior cataract surgery. Nuclear opacities were found in 14% (95% CI 6–26), cortical in 7% (95% CI 2–19), and posterior subcapsular in 5% (95% CI 1–15) of the subjects. The prevalence of lens opacities increased with age, smoking, and cumulative recorded radiation dose. After controlling for age, gender, and smoking, the excess odds ratio for any lens opacity was 0.13 (95% CI -0.02–0.28) per 10 mSv of cumulative radiation dose. CONCLUSIONS: Our preliminary results show cortical and posterior subcapsular lens opacities among physicians exposed to occupational radiation, consistent with recent studies on low dose radiation exposure. A full study with an unexposed reference group for risk estimation is warranted.
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- 2011
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34. BRCA2 Mutations in 154 Finnish Male Breast Cancer Patients
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Kirsi Syrjäkoski, Tuula Kuukasjärvi, Kati Waltering, Karin Haraldsson, Anssi Auvinen, Åke Borg, Tommi Kainu, Olli-P Kallioniemi, and Pasi A. Koivisto
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BRCA2 ,mutation ,male breast cancer ,population ,penetrance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The etiology and pathogenesis of male breast cancer (MBC) are poorly known. This is due to the fact that the disease is rare, and large-scale genetic epidemiologic studies have been difficult to carry out. Here, we studied the frequency of eight recurrent Finnish BRCA2 founder mutations in a large cohort of 154 MBC patients (65% diagnosed in Finland from 1967 to 1996). Founder mutations were detected in 10 patients (6.5%), eight of whom carried the 9346(-2) A>G mutation. Two novel mutations (4075 delGT and 5808 del5) were discovered in a screening of the entire BRCA2 coding region in 34 samples. However, these mutations were not found in the rest of the 120 patients studied. Patients with positive family history of breast and/or ovarian cancer were often BRCA2 mutation carriers (44%), whereas those with no family history showed a low frequency of involvement (3.6%; P < .0001). Finally, we found only one Finnish MBC patient with 999 dell, the most common founder mutation in Finnish female breast cancer (FBC) patients, and one that explains most of the hereditary FBC and MBC cases in Iceland. The variation in BRCA2 mutation spectrum between Finnish MBC patients and FBC patients in Finland and breast cancer patients in Iceland suggests that modifying genetic and environmental factors may significantly influence the penetrance of MBC and FBC in individuals carrying germline BRCA2 mutations in some populations.
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- 2004
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35. Assessing interactions of two loci (rs4242382 and rs10486567) in familial prostate cancer: statistical evaluation of epistasis.
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Li-Sheng Chen, Jean Ching-Yuan Fann, Sherry Yueh-Hsia Chiu, Amy Ming-Fang Yen, Tiina Wahlfors, Teuvo L Tammela, Hsiu-Hsi Chen, Anssi Auvinen, and Johanna Schleutker
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Medicine ,Science - Abstract
Understanding the impact of multiple genetic variants and their interactions on the disease penetrance of familial multiple prostate cancer is very relevant to the overall understanding of carcinogenesis. We assessed the joint effect of two loci on rs4242382 at 8q24 and rs10486567 at 7p15.2 to this end. We analyzed the data from a Finnish family-based genetic study, which was composed of 947 men including 228 cases in 75 families, to evaluate the respective effects of the two loci on the disease penetrance; in particular, the occurrence and number of prostate cancer cases within a family were utilized to evaluate the interactions between the two loci under the additive and multiplicative Poisson regression models. The risk alleles A at rs4242382 (OR = 1.14, 95% CI 1.08-1.19, P
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- 2014
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36. Is the prevalence of overactive bladder overestimated? A population-based study in Finland.
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Kari A O Tikkinen, Teuvo L J Tammela, Aila M Rissanen, Antti Valpas, Heini Huhtala, and Anssi Auvinen
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Medicine ,Science - Abstract
BackgroundIn earlier studies, one in six adults had overactive bladder which may impair quality of life. However, earlier studies have either not been population-based or have suffered from methodological limitations. Our aim was to assess the prevalence of overactive bladder symptoms, based on a representative study population and using consistent definitions and exclusions.Methodology/principal findingsThe aim of the study was to assess the age-standardized prevalence of overactive bladder defined as urinary urgency, with or without urgency incontinence, usually with urinary frequency and nocturia in the absence of urinary tract infection or other obvious pathology. In 2003-2004, a questionnaire was mailed to 6,000 randomly selected Finns aged 18-79 years who were identified from the Finnish Population Register Centre. Information on voiding symptoms was collected using the validated Danish Prostatic Symptom Score, with additional frequency and nocturia questions. Corrected prevalence was calculated with adjustment for selection bias due to non-response. The questionnaire also elicited co-morbidity and socio-demographic information. Of the 6,000 subjects, 62.4% participated. The prevalence of overactive bladder was 6.5% (95% CI, 5.5% to 7.6%) for men and 9.3% (CI, 7.9% to 10.6%) for women. Exclusion of men with benign prostatic hyperplasia reduced prevalence among men by approximately one percentage point (to 5.6% [CI, 4.5% to 6.6%]). Among subjects with overactive bladder, urgency incontinence, frequency, and nocturia were reported by 11%, 23%, and 56% of men and 27%, 38%, and 40% of women, respectively. However, only 31% of men and 35% of women with frequency, and 31% of subjects of both sexes with nocturia reported overactive bladder.Conclusions/significanceOur results indicate a prevalence of overactive bladder as low as 8% suggesting that, in previous studies, occurrence has been overestimated due to vague criteria and selected study populations regarding age distribution and low participation.
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- 2007
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37. Lung cancer incidence attributable to residential radon exposure in Finland
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Olli Kurkela, Jaakko Nevalainen, Salla-Maaria Pätsi, Katja Kojo, Olli Holmgren, Anssi Auvinen, Tampere University, and Health Sciences
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3141 Health care science ,Radiation ,3122 Cancers ,Biophysics ,General Environmental Science - Abstract
This study aimed to estimate (1) the number of avoidable lung cancer cases attributable to residential radon in Finland in 2017, separately by age, sex, dwelling type and smoking status, (2) the impact of residential radon alone and the joint effect of residential radon and smoking on the number of lung cancers and (3) the potential decrease in the number of radon-attributable lung cancers if radon concentrations exceeding specified action levels (100, 200 and 300 Bq m−3) would have been mitigated to those levels. Population-based surveys of radon concentrations and smoking patterns were used. Observed radon levels were contrasted with 25 Bq m−3 representing a realistic minimum level of exposure. Lung cancer risk estimates for radon and smoking were derived from literature. Lastly, the uncertainty due to the estimation of exposure and risk was quantified using a computationally derived uncertainty interval. At least 3% and at most 8% of all lung cancers were estimated as being attributable to residential radon. For small cell carcinoma, the proportion of cases attributable to radon was 8–13%. Among smokers, the majority of the radon-related cases were attributable to the joint effect of radon and smoking. Reduction of radon exposure to 100 Bq m−3 action level would eliminate approximately 30% of radon-attributable cases. Estimates were low compared with the literature, given the (relatively high) radon levels in Finland. This was mainly due to the lower radon levels and higher smoking prevalence in flats than in houses and a more realistic point of comparison, factors which have been ignored in previous studies. The results can guide actions in radon protection and in prevention of lung cancers.
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- 2022
38. First diagnostic results from Gothenburg-2 screening trial
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Ola Bratt, Anssi Auvinen, Tampere University, and Health Sciences
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3141 Health care science ,Nephrology ,Urology - Abstract
publishedVersion Non
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- 2023
39. Lower Urinary Tract Symptoms and Mortality among Finnish Men: The Roles of Symptom Severity and Bother
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Jonne Åkerla, Jori S. Pesonen, Antti Pöyhönen, Juha Koskimäki, Jukka Häkkinen, Heini Huhtala, Anssi Auvinen, and Teuvo L. J. Tammela
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Male ,Urinary Incontinence ,Lower Urinary Tract Symptoms ,Surveys and Questionnaires ,Urology ,Prevalence ,Quality of Life ,Humans ,Female ,Nocturia ,Finland - Abstract
The utility of male lower urinary tract symptoms (LUTS) as mortality risk factors remains unclear. We explored LUTS-associated mortality among Finnish men, evaluating the association of symptom severity and bother with risk of death.A questionnaire including the Danish Prostatic Symptom Score was mailed to a population-based cohort of 3,143 men aged 50, 60 and 70 years in 1994, with repeat surveys in 1999, 2004, 2009 and 2015. The men were followed until the end of 2018. Mortality associated with LUTS was analyzed using time-dependent Cox regression adjusted for age and comorbidity, updating symptom data every 5 years, including interaction terms between symptoms and associated bother.Of the 1,167 men in the analysis, 591 (50.6%) died during the 24-year followup. In analyses of moderate and severe symptoms disregarding bother, overall voiding and storage LUTS, daytime frequency and urgency incontinence were associated with increased mortality: the multivariable-adjusted hazard ratios were 1.19 (95% CI 1.00-1.40), 1.35 (1.13-1.62), 1.31 (1.09-1.58) and 2.19 (1.42-3.37), respectively. In analyses disregarding symptom severity and bother, voiding LUTS were associated with decreased mortality, while daytime frequency and nocturia were associated with increased mortality: the HRs were 0.82 (95% CI 0.67-1.00), 1.31 (95% CI 1.09-1.58) and 1.52 (95% CI 1.21-1.91), respectively. Excess mortality associated with bothersome daytime frequency and nocturia tended to be slightly higher: the HRs were 1.86 (95% CI 1.41-2.47) and 1.88 (95% CI 1.38-2.58), respectively. No significant interactions were found between symptoms and associated bother, however.Moderate and severe LUTS are potential risk factors for mortality, independently of their bother.
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- 2022
40. Data from The Number of Screening Cycles Needed to Reduce Prostate Cancer Mortality in the Finnish Section of the European Randomized Study of Prostate Cancer (ERSPC)
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Anssi Auvinen, Teuvo L.J. Tammela, Ulf-Håkan Stenman, Paula Kujala, Jani Raitanen, Kimmo Taari, Kirsi Talala, Jaakko Nevalainen, and Tomi Pakarainen
- Abstract
Purpose:The European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer mortality by PSA-based screening. The aim of the study is to evaluate screening effect on prostate cancer incidence and mortality in relation to number of screening rounds attended.Experimental Design: The participants in the screening arm of the Finnish trial (31,867 men) were classified according to screening attendance in a time-dependent fashion. Initially, all men in the screening arm were regarded as nonattenders until the first screening attendance, then remained among the once-screened until the second screen and similarly for the possible third round. The control arm was the reference. Follow-up started at randomization and ended at death, emigration, or end of 2013. Prostate cancer incidence and mortality, as well lung cancer and overall mortality were evaluated.Results:Prostate cancer incidence was increased among screened men, but was not directly related to the number of screening rounds. Prostate cancer mortality was decreased in men screened twice or three times, but did not materially differ in those who did not attend the screening, and in men screened once compared with the control arm. The largest mortality reduction was in men screened three times [HR 0.17; 95% confidence interval (CI), 0.09–0.33]. However, a reduction was also seen in lung cancer (HR 0.59; 95% CI, 0.47–0.73) and overall mortality (HR 0.56; 95% CI, 0.52–0.60).Conclusions:Assuming a similar relative reduction being due to selection bias and screening in prostate cancer as other causes of death (40% reduction), approximately half of the observed prostate cancer mortality reduction by repeated screening is likely to be noncausal and a real screening effect may account for up to 40% reduction in men screened three times. Prostate cancer mortality reduction can only be achieved by repeated screening cycles.
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- 2023
41. Data from HOXB13 G84E Mutation in Finland: Population-Based Analysis of Prostate, Breast, and Colorectal Cancer Risk
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Johanna Schleutker, Teuvo L.J. Tammela, Tapio Visakorpi, Anssi Auvinen, Robert L. Vessella, Lauri Aaltonen, Heli Nevanlinna, Anne Kallioniemi, Satu-Leena Laasanen, Outi Kilpivaara, Liisa M. Pelttari, Tommi Rantapero, Leena Saaristo, Tiina Wahlfors, and Virpi H. Laitinen
- Abstract
Background: A recently identified germline mutation G84E in HOXB13 was shown to increase the risk of prostate cancer. In a family-based analysis by The International Consortium for Prostate Cancer Genetics (ICPCG), the G84E mutation was most prevalent in families from the Nordic countries of Finland (22.4%) and Sweden (8.2%).Methods: To further investigate the importance of G84E in the Finns, we determined its frequency in more than 4,000 prostate cancer cases and 5,000 controls. In addition, 986 breast cancer and 442 colorectal cancer (CRC) cases were studied. Genotyping was conducted using TaqMan, MassARRAY iPLEX, and sequencing. Statistical analyses were conducted using Fisher exact test, and overall survival was analyzed using Cox modeling.Results: The frequency of the G84E mutation was significantly higher among patients with prostate cancer and highest among patients with a family history of the disease, hereditary prostate cancer [8.4% vs. 1.0% in controls; OR 8.8; 95% confidence interval (CI), 4.9–15.7]. The mutation contributed significantly to younger age (≤55 years) at onset and high prostate-specific antigen (PSA; ≥20 ng/mL) at diagnosis. An association with increased prostate cancer risk in patients with prior benign prostate hyperplasia (BPH) diagnosis was also revealed. No statistically significant evidence for a contribution in CRC risk was detected, but a suggestive role for the mutation was observed in familial BRCA1/2-negative breast cancer.Conclusions: These findings confirm an increased cancer risk associated with the G84E mutation in the Finnish population, particularly for early-onset prostate cancer and cases with substantially elevated PSA.Impact: This study confirms the overall importance of the HOXB13 G84E mutation in prostate cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 22(3); 452–60. ©2012 AACR.
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- 2023
42. Data from Synergistic Interaction of HOXB13 and CIP2A Predisposes to Aggressive Prostate Cancer
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Johanna Schleutker, Gong-Hong Wei, Fredrik Wiklund, Anssi Auvinen, Teuvo L.J. Tammela, Kirsi M. Talala, Otto Ettala, Liang Wang, Qin Zhang, Ping Gao, and Csilla Sipeky
- Abstract
Purpose:Distinguishing aggressive prostate cancer from indolent disease improves personalized treatment. Although only few genetic variants are known to predispose to aggressive prostate cancer, synergistic interactions of HOXB13 G84E high-risk prostate cancer susceptibility mutation with other genetic loci remain unknown. The purpose of this study was to examine the interplay of HOXB13 rs138213197 (G84E) and CIP2A rs2278911 (R229Q) germline variants on prostate cancer risk.Experimental Design:Genotyping was done in Finnish discovery cohort (n = 2,738) and validated in Swedish (n = 3,132) and independent Finnish (n = 1,155) prostate cancer cohorts. Expression pattern analysis was followed by functional studies in prostate cancer cell models.Results:Interplay of HOXB13 (G84E) and CIP2A (R229Q) variants results in highest observed inherited prostate cancer risk (OR, 21.1; P = 0.000024). In addition, this synergism indicates a significant association of HOXB13 T and CIP2A T dual carriers with elevated risk for high Gleason score (OR, 2.3; P = 0.025) and worse prostate cancer–specific life expectancy (HR, 3.9; P = 0.048), and it is linked with high PSA at diagnosis (OR, 3.30; P = 0.028). Furthermore, combined high expression of HOXB13-CIP2A correlates with earlier biochemical recurrence. Finally, functional experiments showed that ectopic expression of variants stimulates prostate cancer cell growth and migration. In addition, we observed strong chromatin binding of HOXB13 at CIP2A locus and revealed that HOXB13 functionally promotes CIP2A transcription. The study is limited to retrospective Nordic cohorts.Conclusions:Simultaneous presence of HOXB13 T and CIP2A T alleles confers for high prostate cancer risk and aggressiveness of disease, earlier biochemical relapse, and lower disease-specific life expectancy. HOXB13 protein binds to CIP2A gene and functionally promotes CIP2A transcription.
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- 2023
43. Supplementary Table 5 from HOXB13 G84E Mutation in Finland: Population-Based Analysis of Prostate, Breast, and Colorectal Cancer Risk
- Author
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Johanna Schleutker, Teuvo L.J. Tammela, Tapio Visakorpi, Anssi Auvinen, Robert L. Vessella, Lauri Aaltonen, Heli Nevanlinna, Anne Kallioniemi, Satu-Leena Laasanen, Outi Kilpivaara, Liisa M. Pelttari, Tommi Rantapero, Leena Saaristo, Tiina Wahlfors, and Virpi H. Laitinen
- Abstract
PDF file - 43K, Table shows 30 amino acids having the lowest relative solvent accessibilities. The first column indicates the predicted class for the amino acid denoted by the letters B (buried) and E (exposed). Second Column shows the amino acid while in third column the amino acid position is indicated. Fourth column shows the predicted value of relative solvent accessibility (RSA). Fifth column shows the z-fit score of for the RSA prediction which represents the reliability of the RSA prediction. G84 and its proximate amino acids residues are highlighted in red.
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- 2023
44. Appendix Table 1. from The Number of Screening Cycles Needed to Reduce Prostate Cancer Mortality in the Finnish Section of the European Randomized Study of Prostate Cancer (ERSPC)
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Anssi Auvinen, Teuvo L.J. Tammela, Ulf-Håkan Stenman, Paula Kujala, Jani Raitanen, Kimmo Taari, Kirsi Talala, Jaakko Nevalainen, and Tomi Pakarainen
- Abstract
Results of the case-control study
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- 2023
45. Supplementary Table 3 from HOXB13 G84E Mutation in Finland: Population-Based Analysis of Prostate, Breast, and Colorectal Cancer Risk
- Author
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Johanna Schleutker, Teuvo L.J. Tammela, Tapio Visakorpi, Anssi Auvinen, Robert L. Vessella, Lauri Aaltonen, Heli Nevanlinna, Anne Kallioniemi, Satu-Leena Laasanen, Outi Kilpivaara, Liisa M. Pelttari, Tommi Rantapero, Leena Saaristo, Tiina Wahlfors, and Virpi H. Laitinen
- Abstract
PDF file - 38K, Table includes the results of six tolerance predictors and two protein stability predictors included in Pon-P selected for in silico analysis.
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- 2023
46. Supplementary Table 1 from HOXB13 G84E Mutation in Finland: Population-Based Analysis of Prostate, Breast, and Colorectal Cancer Risk
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Johanna Schleutker, Teuvo L.J. Tammela, Tapio Visakorpi, Anssi Auvinen, Robert L. Vessella, Lauri Aaltonen, Heli Nevanlinna, Anne Kallioniemi, Satu-Leena Laasanen, Outi Kilpivaara, Liisa M. Pelttari, Tommi Rantapero, Leena Saaristo, Tiina Wahlfors, and Virpi H. Laitinen
- Abstract
PDF file - 84K, Different sample types included in the analyses are presented in this file.
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- 2023
47. Supplementary Figure 1 from HOXB13 G84E Mutation in Finland: Population-Based Analysis of Prostate, Breast, and Colorectal Cancer Risk
- Author
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Johanna Schleutker, Teuvo L.J. Tammela, Tapio Visakorpi, Anssi Auvinen, Robert L. Vessella, Lauri Aaltonen, Heli Nevanlinna, Anne Kallioniemi, Satu-Leena Laasanen, Outi Kilpivaara, Liisa M. Pelttari, Tommi Rantapero, Leena Saaristo, Tiina Wahlfors, and Virpi H. Laitinen
- Abstract
PDF file - 90K, The first row shows the amino acid sequence. In the second row the predicted secondary structure is illustrated with blue (coil), red (alpha-helix) and green (beta-strand) bars. In the third row numerical value for the confidence of the prediction of secondary structure is indicated by a value ranging from 0-9. The confidence value of zero indicates the lowest possible confidence of prediction while 9 is represents the highest value of confidence. The values in the fourth row represents the relative solvent accessibility. Zero indicates a 0-9% relative solvent accessibility while the value of 9 indicates 90-100% solvent accessibility. The fifth row indicates the confidence value for the prediction of relative solvent accessibility ranging from 0-9. The confidence value of zero indicates the lowest possible confidence of prediction while 9 is represents the highest value of confidence.
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- 2023
48. Supplementary Table 2 from HOXB13 G84E Mutation in Finland: Population-Based Analysis of Prostate, Breast, and Colorectal Cancer Risk
- Author
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Johanna Schleutker, Teuvo L.J. Tammela, Tapio Visakorpi, Anssi Auvinen, Robert L. Vessella, Lauri Aaltonen, Heli Nevanlinna, Anne Kallioniemi, Satu-Leena Laasanen, Outi Kilpivaara, Liisa M. Pelttari, Tommi Rantapero, Leena Saaristo, Tiina Wahlfors, and Virpi H. Laitinen
- Abstract
PDF file - 47K, Presentation of segregation analysis.
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- 2023
49. Supplementary data_310718 from Synergistic Interaction of HOXB13 and CIP2A Predisposes to Aggressive Prostate Cancer
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Johanna Schleutker, Gong-Hong Wei, Fredrik Wiklund, Anssi Auvinen, Teuvo L.J. Tammela, Kirsi M. Talala, Otto Ettala, Liang Wang, Qin Zhang, Ping Gao, and Csilla Sipeky
- Abstract
Supplementary Table 1. Clinical characteristics of Finnish prostate cancer patients Supplementary Table 2. Tumour Stage Group (TSG) definitions Supplementary Table 3. Follow-up characteristics used in survival analyses of Finnish prostate cancer patients Supplementary Table 4. Primer sequences used in quantitative RT-PCR reactions Supplementary Table 5. Assessment of PrCa risk due to the combination of HOXB13 T and CIP2A T in dual carriers relative to the risk in non-carriers Supplementary Table 6 Time-to-PrCa event of HOXB13 rs138213197 and CIP2A rs2278911 Supplementary Table 7 Association of HOXB13 G84E and CIP2A R229Q carrier status and clinical features of prostate cancer subgroups Supplementary Table 8. Association of HOXB13 and CIP2A carrier status and combined modality stage of prostate cancer patients according to ERSPC Supplementary Table 9. P-values for Figure1, Figure 2 and Supplementary figure 2. Supplementary figure 1. Higher mRNA expression pattern of HOXB13-CIP2A correlated with increased risk of prostate cancer biochemical recurrence. Supplementary figure 2. Effects of HOXB13 G84E and CIP2A R229Q variants on prostate cell migration. Supplementary figure 3. ChIP-qPCR in VCaP cell line Supplementary figure 4. Overexpression of HOXB13 G84E and CIP2A R229Q variants promotes cell proliferation.
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- 2023
50. Prostate cancer incidence in men with prostate-specific antigen below 3 ng/mL : The Finnish Randomized Study of Screening for Prostate Cancer
- Author
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Idris Olasunmbo Ola, Kirsi Talala, Teuvo Tammela, Kimmo Taari, Teemu Murtola, Paula Kujala, Jani Raitanen, Anssi Auvinen, HUS Abdominal Center, Clinicum, Urologian yksikkö, Helsinki University Hospital Area, Research Programs Unit, Tampere University, Clinical Medicine, Department of Pathology, and Health Sciences
- Subjects
Cancer screening ,Cancer Research ,Oncology ,3122 Cancers ,Randomized controlled trials ,Rescreening intervals ,Prostate cancer incidence ,Prostate-specific antigen - Abstract
Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) can reduce PCa mortality, but also involves over-detection of low-risk disease with potential adverse effects. We evaluated PCa incidence among men with PSA below 3 ng/mL and no PCa diagnosis at the first screening round of the Finnish Randomized Study of Screening for PCa. Follow-up started at the first screening attendance and ended at PCa diagnosis, emigration, death, or the common closing date (December 2016), whichever came first. Cox regression analysis was used to estimate hazard ratios and their confidence intervals (CI). Among men with PSA
- Published
- 2023
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