Anssi Auvinen

Publications (185)1066 Total impact

• Source

  Available from: Kaja Rahu

  Article: Chernobyl cleanup workers from Estonia: follow-up for cancer incidence and mortality.

  Kaja Rahu, Anssi Auvinen, Timo Hakulinen, Mare Tekkel, Peter D Inskip, Evelyn J Bromet, John D Boice Jr, Mati Rahu
  [show abstract] [hide abstract]
  ABSTRACT: This study examined cancer incidence (1986-2008) and mortality (1986-2011) among the Estonian Chernobyl cleanup workers in comparison with the Estonian male population. The cohort of 4810 men was followed through nationwide population, mortality and cancer registries. Cancer and death risks were measured by standardised incidence ratio (SIR) and standardised mortality ratio (SMR), respectively. Poisson regression was used to analyse the effects of year of arrival, duration of stay and time since return on cancer and death risks. The SIR for all cancers was 1.06 with 95% confidence interval 0.93-1.20 (232 cases). Elevated risks were found for cancers of the pharynx, the oesophagus and the joint category of alcohol-related sites. No clear evidence of an increased risk of thyroid cancer, leukaemia or radiation-related cancer sites combined was apparent. The SMR for all causes of death was 1.02 with 95% confidence interval 0.96-1.08 (1018 deaths). Excess mortality was observed for mouth and pharynx cancer, alcohol-related cancer sites together and suicide. Duration of stay rather than year of arrival was associated with increased mortality. Twenty-six years of follow-up of this cohort indicates no definite health effects attributable to radiation, but the elevated suicide risk has persisted.
  Journal of Radiological Protection 03/2013; 33(2):395-411. · 1.39 Impact Factor
• Article: Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.

  Rosalind A Eeles, Ali Amin Al Olama, Sara Benlloch, Edward J Saunders, Daniel A Leongamornlert, Malgorzata Tymrakiewicz, Maya Ghoussaini, Craig Luccarini, Joe Dennis, Sarah Jugurnauth-Little, [......], Sofia Maia, Paula Paulo, Ethan Lange, Kathleen A Cooney, Antonis C Antoniou, Daniel Vincent, François Bacot, Daniel C Tessier, Zsofia Kote-Jarai, Douglas F Easton
  [show abstract] [hide abstract]
  ABSTRACT: Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
  Nature Genetics 03/2013; 45(4):385-391. · 35.53 Impact Factor
• Source

  Available from: Ulf-Håkan Stenman

  Article: Prostate Cancer Mortality in the Finnish Randomized Screening Trial.

  Tuomas P Kilpeläinen, Teuvo L Tammela, Nea Malila, Matti Hakama, Henrikki Santti, Liisa Määttänen, Ulf-Håkan Stenman, Paula Kujala, Anssi Auvinen
  [show abstract] [hide abstract]
  ABSTRACT: Background Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality.MethodsA total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0ng/mL or 3.0 to 3.99ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided.ResultsPC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). No statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms.Conclusions At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.
  CancerSpectrum Knowledge Environment 03/2013; · 14.07 Impact Factor
• Article: Excess mortality in the evaluation of a screening trial - important to account for selective participation.

  Ries Kranse, Pim van Leeuwen, Timo Hakulinen, Jonas Hugosson, Teuvo L Tammela, Stefano Ciatto, Monique J Roobol, Marco Zappa, Gunnar Aus, Chris H Bangma, Sue Moss, Anssi Auvinen
  [show abstract] [hide abstract]
  ABSTRACT: Objective In addition to disease-specific mortality, a randomized controlled cancer screening trial may be evaluated in terms of excess mortality, in which case no patient-specific information on causes of death is needed. We studied the effect of not accounting for attendance on the calculated excess mortality in a prostate cancer screening trial.Methods The numerator of the excess mortality rate related to prostate cancer diagnoses in each study arm equals the excess number of deaths observed in the cancer patients. The estimation of the expected number of deaths in the absence of the prostate cancer diagnoses has to account for the self-selection of those participating in the trial, particularly if the proportion of non-participants is substantial.Setting The European prostate cancer screening trial (ERSPC).Results In the screening arm, non-attendees had roughly twice the mortality rate of attendees. Approximately twice as many cancers were detected in the screening arm compared with the control arm, primarily in attendees. Unless attendance is properly accounted for, the expected mortality of prostate cancer patients in the screening arm is overestimated by 0.9-3.6 deaths per 1000 person-years.Conclusions Attendees have a lower all-cause mortality rate (are healthier) and a higher probability of a prostate cancer diagnosis than non-attendees and the men randomized to the control arm. If attendance is not accounted for, the excess mortality and the between-arm excess mortality rate ratio are underestimated and screening is considered more effective than it actually is. These effects may be sizeable, notably if non-attendance is common. Correcting for attendance status is important in the calculation of the excess mortality rate in prostate cancer patients that can be used in conjunction with a disease-specific mortality analysis in a randomized controlled cancer screening trial.
  Journal of Medical Screening 02/2013; · 1.69 Impact Factor
• Article: Impacts of a population based prostate cancer screening programme on excess all-mortality rates in men with prostate cancer: a randomized controlled trial.

  Pim J van Leeuwen, Ries Kranse, Timo Hakulinen, Jonas Hugosson, Teuvo L Tammela, Stefano Ciatto, Monique J Roobol, Marco Zappa, Harry J de Koning, Chris H Bangma, Sue M Moss, Anssi Auvinen, Fritz H Schröder
  Journal of Medical Screening 02/2013; · 1.69 Impact Factor
• Article: Risk Factors for Skin Cancer among Finnish Airline Cabin Crew.

  Katja Kojo, Mika Helminen, Eero Pukkala, Anssi Auvinen
  [show abstract] [hide abstract]
  ABSTRACT: Increased incidence of skin cancers among airline cabin crew has been reported in several studies. We evaluated whether the difference in risk factor prevalence between Finnish airline cabin crew and the general population could explain the increased incidence of skin cancers among cabin crew, and the possible contribution of estimated occupational cosmic radiation exposure. A self-administered questionnaire survey on occupational, host, and ultraviolet radiation exposure factors was conducted among female cabin crew members and females presenting the general population. The impact of occupational cosmic radiation dose was estimated in a separate nested case-control analysis among the participating cabin crew (with 9 melanoma and 35 basal cell carcinoma cases). No considerable difference in the prevalence of risk factors of skin cancer was found between the cabin crew (N = 702) and the general population subjects (N = 1007) participating the study. The mean risk score based on all the conventional skin cancer risk factors was 1.43 for cabin crew and 1.44 for general population (P = 0.24). Among the cabin crew, the estimated cumulative cosmic radiation dose was not related to the increased skin cancer risk [adjusted odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.57-1.00]. The highest plausible risk of skin cancer for estimated cosmic radiation dose was estimated as 9% per 10 mSv. The skin cancer cases had higher host characteristics scores than the non-cases among cabin crew (adjusted OR = 1.43, 95% CI: 1.01-2.04). Our results indicate no difference between the female cabin crew and the general female population in the prevalence of factors generally associated with incidence of skin cancer. Exposure to cosmic radiation did not explain the excess of skin cancer among the studied cabin crew in this study.
  Annals of Occupational Hygiene 01/2013; · 1.95 Impact Factor
• Article: HOXB13 G84E mutation in Finland; population-based analysis of prostate, breast and colorectal cancer risk.

  Virpi H Laitinen, Tiina Wahlfors, Leena Saaristo, Tommi Rantapero, Liisa M Pelttari, Outi Kilpivaara, Satu-Leena Laasanen, Anne Kallioniemi, Heli Nevanlinna, Lauri A Aaltonen, Robert L Vessella, Anssi Auvinen, Tapio Visakorpi, Teuvo L J Tammela, Johanna Schleutker
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: A recently identified germline mutation G84E in HOXB13 was shown to increase the risk of prostate cancer (PrCa). In a family-based analysis by The International Consortium for Prostate Cancer Genetics, the proportion of G84E mutation was highest 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 over 4000 PrCa cases and 5000 controls. In addition, the frequency was characterized in 986 breast (BrCa) and 442 colon cancer (CRC) cases. Genotyping was performed using TaqMan®, MassARRAY iPLEX and sequencing. Statistical analyses were performed using Fisher's exact test and overall survival was analyzed using Cox modeling. RESULTS: Frequency was significantly higher among patients with PrCa, and highest among patients with family history of the disease, i.e. hereditary PrCa (8.4% vs. 1.0% in controls; odds ratio 8.8; 95% CI 4.9-15.7). The mutation contributed significantly to younger age (≤55 years) at onset and high PSA (≥20 ng/ml) at diagnosis. An association with increased PrCa risk in patients with prior BPH diagnosis was also revealed. No statistically significant evidence for G84E contribution in CRC risk was detected but a suggestive role for the mutation was seen in familial BrCa negative for BRCA1/2 founder mutations. CONCLUSIONS: These findings confirm the increased risk effect of G84E mutation in the Finnish population, particularly for early-onset PrCa and cases with substantially elevated PSA. Impact: This study confirms the overall importance of the HOXB13 G84E mutation in prostate cancer susceptibility.
  Cancer Epidemiology Biomarkers &amp Prevention 01/2013; · 4.12 Impact Factor
• Article: Reply from Authors re: Jonathan Bergman, Mark S. Litwin. The Henderson-Hasselbalch Equation for Urologists. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2012.12.021: Health-related Quality-of-life Scores from the Finnish Trial of Screening for Prostate Cancer Offer One Useful Contribution.

  Neill Booth, Pekka Rissanen, Teuvo L J Tammela, Liisa Määttänen, Kimmo Taari, Anssi Auvinen
  European urology 01/2013; · 7.67 Impact Factor
• Article: Health-Related Quality of Life in the Finnish Trial of Screening for Prostate Cancer.

  Neill Booth, Pekka Rissanen, Teuvo L J Tammela, Liisa Määttänen, Kimmo Taari, Anssi Auvinen
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Evidence of the potential impact of systematic screening for prostate cancer (PCa) on health-related quality of life (HRQoL) at a population-based level is currently scarce. OBJECTIVE: This study aims to quantify the long-term HRQoL impact associated with screening for PCa. DESIGN, SETTING, AND PARTICIPANTS: Postal questionnaire surveys were conducted in 1998, 2000, 2004, and 2011 among men in the Finnish PCa screening trial diagnosed with PCa (total n=7011) and among a random subsample of the trial population (n=2200). In 2011, for example, 1587 responses were received from men with PCa in the screening arm and 1706 from men in the control arm. In addition, from the trial subsample, 549 men in the screening arm and 539 in the control arm provided responses. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Health-state-value scores were compared between the intervention and control arms using three distinct HRQoL measures (15D, EQ-5D, and SF-6D), and statistical significance was assessed using t tests. In addition, differences over repeated assessments of HRQoL between groups were evaluated using generalised estimating equations. RESULTS AND LIMITATIONS: In the 2011 survey, a small but statistically significant difference emerged between the trial arms among men diagnosed with PCa (mean scores, screening vs control arm: 15D: 0.872 vs 0.866, p=0.14; EQ-5D: 0.852 vs 0.831, p=0.03; and SF-6D: 0.763 vs 0.756, p=0.06). Such differences in favour of the screening arm were not found among the sample of men from the trial (15D: 0.889 vs 0.892, p=0.62; EQ-5D: 0.831 vs 0.852, p=0.08; and SF-6D: 0.775 vs 0.777, p=0.88). The slight advantage with screening among men with PCa was reasonably consistent across time in the longitudinal analysis and was strongest among men with early-stage disease. CONCLUSIONS: These results show some long-term HRQoL benefit from screening for men with PCa but suggest little impact overall in the trial population.
  European urology 11/2012; · 7.67 Impact Factor
• Article: Empirical evaluation of grouping of lower urinary tract symptoms: principal component analysis of Tampere Ageing Male Urological Study data.

  Antti Pöyhönen, Jukka T Häkkinen, Juha Koskimäki, Matti Hakama, Teuvo L J Tammela, Anssi Auvinen
  [show abstract] [hide abstract]
  ABSTRACT: What's known on the subject? and What does the study add? The ICS has divided LUTS into three groups: storage, voiding and post-micturition symptoms. The classification is based on anatomical, physiological and urodynamic considerations of a theoretical nature. We used principal component analysis (PCA) to determine the inter-correlations of various LUTS, which is a novel approach to research and can strengthen existing knowledge of the phenomenology of LUTS. After we had completed our analyses, another study was published that used a similar approach and results were very similar to those of the present study. We evaluated the constellation of LUTS using PCA of the data from a population-based study that included >4000 men. In our analysis, three components emerged from the 12 LUTS: voiding, storage and incontinence components. Our results indicated that incontinence may be separate from the other storage symptoms and post-micturition symptoms should perhaps be regarded as voiding symptoms. OBJECTIVE: To determine how lower urinary tract symptoms (LUTS) relate to each other and assess if the classification proposed by the International Continence Society (ICS) is consistent with empirical findings. MATERIALS AND METHODS: The information on urinary symptoms for this population-based study was collected using a self-administered postal questionnaire in 2004. The questionnaire was sent to 7470 men, aged 30-80 years, from Pirkanmaa County (Finland), of whom 4384 (58.7%) returned the questionnaire. The Danish Prostatic Symptom Score-1 questionnaire was used to evaluate urinary symptoms. Principal component analysis (PCA) was used to evaluate the inter-correlations among various urinary symptoms. RESULTS: The PCA produced a grouping of 12 LUTS into three categories consisting of voiding, storage and incontinence symptoms. Post-micturition symptoms were related to voiding symptoms, but incontinence symptoms were separate from storage symptoms. In the analyses by age group, similar categorization was found at ages 40, 50, 60 and 80 years, but only two groups of symptoms emerged among men aged 70 years. The prevalence among men aged 30 was too low for meaningful analysis. CONCLUSIONS: This population-based study suggests that LUTS can be divided into three subgroups consisting of voiding, storage and incontinence symptoms based on their inter-correlations. Our empirical findings suggest an alternative grouping of LUTS. The potential utility of such an approach requires careful consideration.
  BJU International 10/2012; · 2.84 Impact Factor
• Article: Mortality by clinical characteristics in a tertiary care cohort of adult patients with chronic epilepsy.

  Olli Nevalainen, Anssi Auvinen, Hanna Ansakorpi, Miia Artama, Jani Raitanen, Jouko Isojärvi
  [show abstract] [hide abstract]
  ABSTRACT: The authors evaluated the contribution of various clinical characteristics to mortality risk and underlying causes of death among all adult patients with epilepsy seen at the Department of Neurology, Oulu University Hospital in Finland during 1996 and 1997. Hazard ratios (HRs) for mortality in 1998-2006 relative to a population-based reference cohort were estimated using Cox modeling, with adjustment for age and gender. The HR for total mortality was 2.66 (95% confidence interval [CI] 2.09-3.39). Infectious etiology of epilepsy (HR 5.77, 95% CI 2.52-13.2) and a seizure frequency of ≥1 per month (HR 4.42, 95% CI 3.00-6.52) related to high risks of death. Cancer (21%), ischemic heart disease (15%), and accidents (12%) caused most of the potential years of life lost. Despite recent advances in treatment of epilepsy and improved seizure control, chronic epilepsy still carries a substantially increased risk of death.
  Epilepsia 10/2012; · 3.96 Impact Factor
• Article: Impact of obesity on urinary storage symptoms: results from the FINNO Study.

  Camille P Vaughan, Anssi Auvinen, Rufus Cartwright, Theodore M Johnson, Riikka M Tähtinen, Mika A Ala-Lipasti, Teuvo L J Tammela, Alayne D Markland, Kristian Thorlund, Kari A O Tikkinen
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSE: Urinary storage symptoms are the most common and most bothersome urinary symptoms. Many studies on the relation between body weight and urinary symptoms have focused on urinary incontinence in women. We evaluated the association of obesity with urinary storage symptoms in a population-based study of men and women, aged 18-79. MATERIALS AND METHODS: Questionnaires were mailed to 6,000 adults randomly identified from the Finnish Population Register. Self-reported height and weight were used to calculate body mass index (BMI). Urinary frequency, nocturia, urgency, stress urinary incontinence (SUI), and urgency urinary incontinence (UUI) were assessed using validated instruments. Multivariate logistic regression analyses (adjusted for age, comorbidity, medications, socio-demographic, lifestyle, and reproductive factors) were performed to evaluate associations between BMI and each symptom. RESULTS: Of the 6,000 individuals approached, 3,727 participated (62.4% response; 53.7% women). In men and women, obesity was associated with nocturia (adjusted OR 2.0 [95% CI: 1.2-3.3] for men; OR 2.4 [1.5-3.8] for women) but not with urgency (adjusted OR 1.2 [0.7-2.3] for men: OR 1.2 [0.7-2.1] for women). In men, obesity was also associated with urinary frequency (OR 2.0 [1.0-3.9]), and in women with SUI (OR 1.9 [1.2-3.0]) and UUI (OR 3.0 [1.2-7.4] whereas the number of men with SUI or UUI was insufficient for precise analyses. CONCLUSIONS: This study extends previous research by providing symptom-specific associations between obesity and urinary storage symptoms in a population-based sample of men and women. Obesity impacts individual urinary storage symptoms differently, and these associations may be influenced by gender.
  The Journal of urology 10/2012; · 4.02 Impact Factor
• Article: Use of aspirin, but not other non-steroidal anti-inflammatory drugs is associated with decreased prostate cancer risk at the population level.

  Thea Veitonmäki, Teuvo L J Tammela, Anssi Auvinen, Teemu J Murtola
  [show abstract] [hide abstract]
  ABSTRACT: The cyclooxygenase 2 (COX-2) enzyme overexpression in prostate cancer has led to the hypothesis that COX-2 inhibition may reduce prostate cancer growth. Some previous studies have linked the usage of COX-2 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) with a decreased prostate cancer risk. We estimated the association between cumulative COX-2 inhibition by NSAID usage and prostate cancer risk at population level. All new prostate cancer cases in Finland during 1995-2002 and matched controls (24,657 case-control pairs) were identified from national registries. Detailed information on medication purchases was obtained from a national prescription database. A total cumulative COX-2 inhibition value was calculated based on total cumulative mg amount of each NSAID drug and the drug-specific COX-1/COX-2 inhibition ratio. Prostate cancer risk was analysed with propensity score-matched conditional logistic regression model. In total, 53.8% of the cases and 46.5% of the controls had any prescription-use of NSAIDs, while 8.1% and 7.9%, respectively, had used aspirin. Compared to the non-users, any NSAID use was associated with an elevated overall prostate cancer risk (46.4% versus 53.6%, respectively; odds ratio [OR] 1.3, 95% confidence interval [CI] 1.3, 1.4) and risk of advanced cancer (11.8% versus 14.1%; OR 1.6, 95% CI 1.5, 1.8). The risk remained elevated despite the amount of cumulative COX-2 inhibition. In a separate analysis, the risk increase was similar for each NSAID with the exception of aspirin, which was associated with a decreased overall prostate cancer risk (OR 0.90, 95% CI 0.84, 0.96) in a dose-dependent fashion. NSAID use is associated with an increased prostate cancer risk at the population level regardless of the COX-2 inhibition. This may be explained by systematic differences between prescription NSAID users and non-users. In contrast, aspirin use is associated with a decreased overall prostate cancer risk. Further studies on aspirin and prostate cancer will be needed.
  European journal of cancer (Oxford, England: 1990) 10/2012; · 4.12 Impact Factor
• Article: A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease.

  Ali Amin Al Olama, Zsofia Kote-Jarai, Fredrick R Schumacher, Fredrik Wiklund, Sonja I Berndt, Sara Benlloch, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, [......], Shintaro Narita, Guang-Wen Cao, Chavdar Slavov, Vanio Mitev, Stephen Chanock, Henrik Gronberg, Christopher A Haiman, Peter Kraft, Douglas F Easton, Rosalind A Eeles
  [show abstract] [hide abstract]
  ABSTRACT: Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four genome-wide association studies (GWAS) including 5,953 cases of aggressive PrCa and 11,463 controls (men without PrCa). We computed association tests for ~2.6M SNPs and followed up the most significant SNPs by genotyping 49,121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa (OR=1.12 (95% CI 1.03-1.21), P=1.4x10(-8)). This report describes a genetic variant which is associated with aggressive prostate cancer, which is a type of prostate cancer associated with a poorer prognosis.
  Human Molecular Genetics 10/2012; · 7.64 Impact Factor
• Article: Loss of SUFU Function in Familial Multiple Meningioma.

  Mervi Aavikko, Song-Ping Li, Silva Saarinen, Pia Alhopuro, Eevi Kaasinen, Ekaterina Morgunova, Yilong Li, Kari Vesanen, Miriam J Smith, D Gareth R Evans, Minna Pöyhönen, Anne Kiuru, Anssi Auvinen, Lauri A Aaltonen, Jussi Taipale, Pia Vahteristo
  [show abstract] [hide abstract]
  ABSTRACT: Meningiomas are the most common primary tumors of the CNS and account for up to 30% of all CNS tumors. An increased risk of meningiomas has been associated with certain tumor-susceptibility syndromes, especially neurofibromatosis type II, but no gene defects predisposing to isolated familial meningiomas have thus far been identified. Here, we report on a family of five meningioma-affected siblings, four of whom have multiple tumors. No NF2 mutations were identified in the germline or tumors. We combined genome-wide linkage analysis and exome sequencing, and we identified in suppressor of fused homolog (Drosophila), SUFU, a c.367C>T (p.Arg123Cys) mutation segregating with the meningiomas in the family. The variation was not present in healthy controls, and all seven meningiomas analyzed displayed loss of the wild-type allele according to the classic two-hit model for tumor-suppressor genes. In silico modeling predicted the variant to affect the tertiary structure of the protein, and functional analyses showed that the activity of the altered SUFU was significantly reduced and therefore led to dysregulated hedgehog (Hh) signaling. SUFU is a known tumor-suppressor gene previously associated with childhood medulloblastoma predisposition. Our genetic and functional analyses indicate that germline mutations in SUFU also predispose to meningiomas, particularly to multiple meningiomas. It is possible that other genic mutations resulting in aberrant activation of the Hh pathway might underlie meningioma predisposition in families with an unknown etiology.
  The American Journal of Human Genetics 09/2012; 91(3):520-6. · 10.60 Impact Factor
• Source

  Available from: Marie-Louise Essink-Bot

  Article: Quality-of-life effects of prostate-specific antigen screening.

  Eveline A M Heijnsdijk, Elisabeth M Wever, Anssi Auvinen, Jonas Hugosson, Stefano Ciatto, Vera Nelen, Maciej Kwiatkowski, Arnauld Villers, Alvaro Páez, Sue M Moss, [......], Tuukka Mäkinen, Sigrid Carlsson, Ida J Korfage, Marie-Louise Essink-Bot, Suzie J Otto, Gerrit Draisma, Chris H Bangma, Monique J Roobol, Fritz H Schröder, Harry J de Koning
  [show abstract] [hide abstract]
  ABSTRACT: After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain. On the basis of ERSPC follow-up data, we used Microsimulation Screening Analysis (MISCAN) to predict the number of prostate cancers, treatments, deaths, and quality-adjusted life-years (QALYs) gained after the introduction of PSA screening. Various screening strategies, efficacies, and quality-of-life assumptions were modeled. Per 1000 men of all ages who were followed for their entire life span, we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and a total of 73 life-years gained (average, 8.4 years per prostate-cancer death avoided). The number of QALYs that were gained was 56 (range, -21 to 97), a reduction of 23% from unadjusted life-years gained. To prevent one prostate-cancer death, 98 men would need to be screened and 5 cancers would need to be detected. Screening of all men between the ages of 55 and 74 would result in more life-years gained (82) but the same number of QALYs (56). The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects. Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made. (Funded by the Netherlands Organization for Health Research and Development and others.).
  New England Journal of Medicine 08/2012; 367(7):595-605. · 53.30 Impact Factor
• Article: Prevalence and bother of postmicturition dribble in Finnish men aged 30-80 years: Tampere Ageing Male Urologic Study (TAMUS).

  Antti Pöyhönen, Anssi Auvinen, Juha Koskimäki, Matti Hakama, Teuvo L J Tammela, Jukka T Häkkinen
  [show abstract] [hide abstract]
  ABSTRACT: Abstract Objective. The aim of this study was to determine the prevalence and bother of postmicturition dribble in relation to age in the male population. Material and methods. Information for a population-based study was collected by means of a mailed self-administered questionnaire, which was returned by 4384 men out of 7470 (58.7%). The participants were men aged 30-80 years from the Pirkanmaa Region in Finland. The Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire was used to evaluate their urinary symptoms. SPSS was used in the data analysis. Two-sided chi-squared test and Kendall tau-b test were used for analysis. Results. The overall prevalence of postmicturition dribble was 58.1% (95% confidence interval 56.6-59.6). Prevalence of postmicturition dribble increased with age (p < 0.001). In men aged 60-80 years, two-thirds reported postmicturition dribble and approximately one out of four had dribbling into their trousers after voiding. In the 30-year-old group, over 40% reported postmicturition dribble and almost one out of five had also dribbling into their trousers. One out of five men in the 30-year-old group reported minor bother; the proportion of men reporting bother increased with age to one-third of the men in the oldest cohort (p < 0.001). Conclusions. The prevalence of the postmicturition dribble was found to be high in this survey. Half of the 30-year-old men and two-thirds of the men aged 60-80 years had postmicturition dribble. Dribbling into trousers increased with age but as a severe symptom, it was rare (0.5%). Minor problems from postmicturition dribble were common, but major bother occurred seldom (1.1%).
  Scandinavian Journal of Urology and Nephrology 07/2012; · 0.99 Impact Factor
• Article: Effect of intervention on decision making of treatment for disease progression, prostate-specific antigen biochemical failure and prostate cancer death.

  Rex C-C Huang, Anssi Auvinen, Matti Hakama, Teuvo L J Tammela, Martti Ala-Opas, Mikael Leppilahti, Timo Vornanen, Hsiu-Hsi Chen
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Patient preference for the choice of treatment modality for prostate cancer has increasingly gained attention. OBJECTIVE: To assess the impact of client-oriented decision on long-term mortality, disease progression and biochemical failure compared with standard treatment protocol (TP). METHODS: With data from a Finnish multicentre, randomized controlled trial with two arms [104 in the enhanced patient participation (EPP) arm and 106 in the TP arm], disease-specific and disease-free survival, biochemical failure with elevated prostate-specific antigen (PSA) level and disease progression were compared between the two arms using Wilcoxon test and also Cox proportional hazards regression model. RESULTS: Patients in the EPP arm had a higher risk of death by 37% [HR, 1.37 (0.87-2.17)] compared with those in the TP arm. Patients in the EPP arm were at increased risk of having biochemical failure by 14% [HR, 1.14 (0.72-1.79)] and for having disease progression by 2% [HR, 1.02 (0.61-1.70)] compared with those in the TP arm. All the differences were non-significant. CONCLUSIONS: Patients actively involved in the choice of treatment had higher risk of prostate cancer death but only slightly increased risk of biochemical failure and clinical disease progression. These findings would provide a good reference when patient autonomy for the choice of treatment modality is addressed.
  Health expectations: an international journal of public participation in health care and health policy 07/2012; · 1.80 Impact Factor
• Article: Evaluation of breast cancer service screening programme with a Bayesian approach: mortality analysis in a Finnish region

  Jenny Chia-Yun Wu, Ahti Anttila, Amy Ming-Fang Yen, Matti Hakama, Irma Saarenmaa, Tytti Sarkeala, Nea Malila, Anssi Auvinen, Sherry Yueh-Hsia Chiu, Tony Hsiu-Hsi Chen
  [show abstract] [hide abstract]
  ABSTRACT: Evaluation of long-term effectiveness of population-based breast cancer service screening program in a small geographic area may suffer from self-selection bias and small samples. Under a prospective cohort design with exposed and non-exposed groups classified by whether women attended the screen upon invitation, we proposed a Bayesian acyclic graphic model for correcting self-selection bias with or without incorporation of prior information derived from previous studies with an identical screening program in Sweden by chronological order and applied it to an organized breast cancer service screening program in Pirkanmaa center of Finland. The relative mortality rate of breast cancer was 0.27 (95% CI 0.12–0.61) for the exposed group versus the non-exposed group without adjusting for self-selection bias. With adjustment for selection-bias, the adjusted relative mortality rate without using previous data was 0.76 (95% CI 0.49–1.15), whereas a statistically significant result was achieved [0.73 (95% CI 0.57–0.93)] with incorporation of previous information. With the incorporation of external data sources from Sweden in chronological order, adjusted relative mortality rate was 0.67 (0.55–0.80). We demonstrated how to apply a Bayesian acyclic graphic model with self-selection bias adjustment to evaluating an organized but non-randomized breast cancer screening program in a small geographic area with a significant 27% mortality reduction that is consistent with the previous result but more precise. Around 33% mortality was estimated by taking previous randomized controlled data from Sweden. KeywordsBreast cancer screening-Self-selection bias-Bayesian acyclic graphic model-Mortality reduction
  Breast Cancer Research and Treatment 04/2012; 121(3):671-678. · 4.43 Impact Factor
• Article: Does the imprecise definition of overactive bladder serve commercial rather than patient interests?

  Kari A O Tikkinen, Anssi Auvinen
  European urology 04/2012; 61(4):746-8; discussion 749-50. · 7.67 Impact Factor