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Jussila A.,University of Tampere | Jussila A.,Seinajoki Central Hospital | Virta L.J.,Social Insurance Institution | Pukkala E.,Institute for Statistical and Epidemiological Cancer Research | And 2 more authors.
Journal of Crohn's and Colitis | Year: 2014

Background and aim: Increased mortality has been reported in Crohn's disease (CD) but mostly not in ulcerative colitis (UC). We evaluated the overall and cause-specific mortality in a nationwide cohort of patients with inflammatory bowel disease (IBD) in Finland. Methods: A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the Special Reimbursement register were diagnosed 1987-1993 and 2000-2007 and followed up to the end of 2010 by collating these figures with the national computerized Cause-of-Death Register of Statistics Finland. In each cause-of-death category, the number of deaths reported was compared to that expected in general population, and expressed as a standardized mortality ratio (SMR). Results: Overall mortality was increased among patients with CD (SMR 1.33, 95% confidence interval 1.21-1.46) and UC (1.10, 1.05-1.15). SMR was significantly increased for gastrointestinal causes in CD (6.53, 4.91-8.52) and UC (2.81, 2.32-3.34). Patients with UC were found also to have increased SMR from pulmonary (1.24, 1.02-1.46) and cardiovascular disease (1.14, 1.06-1.22) and cancers of the colon (1.90, 1.38-2.55), rectum (1.79, 1.14-2.69) and biliary tract (5.65, 3.54-8.54), whereas SMR from alcohol-related deaths was decreased (0.54, 0.39-0.71). Patients with CD had a significantly increased SMR for pulmonary diseases (2.01, 1.39-2.80), infections (4.27, 2.13-7.63) and cancers of the biliary tract (4.51, 1.23-11.5) and lymphoid and hematopoietic tissue (2.95, 1.85-4.45). Conclusions: In this Finnish nationwide study increased overall mortality in both CD and UC was observed. The excess mortality of 14 % in IBD is mainly due to deaths related to inflammation in the gut. © 2014 European Crohn's and Colitis Organisation.


Deltour I.,International Agency of Research on Cancer | Deltour I.,Danish Cancer Society | Auvinen A.,University of Tampere | Auvinen A.,Radiation and Nuclear Safety Authority | And 5 more authors.
Epidemiology | Year: 2012

Background: Some case-control studies have reported increased risks of glioma associated with mobile phone use. If true, this would ultimately affect the time trends for incidence rates (IRs). Correspondingly, lack of change in IRs would exclude certain magnitudes of risk. We investigated glioma IR trends in the Nordic countries, and compared the observed with expected incidence rates under various risk scenarios. Methods: We analyzed annual age-standardized incidence rates in men and women aged 20 to 79 years during 1979-2008 using joinpoint regression (35,250 glioma cases). Probabilities of detecting various levels of relative risk were computed using simulations. Results: For the period 1979 through 2008, the annual percent change in incidence rates was 0.4% (95% confidence interval = 0.1% to 0.6%) among men and 0.3% (0.1% to 0.5%) among women. Incidence rates have decreased in young men (20-39 years) since 1987, remained stable in middle-aged men (40-59 years) throughout the 30-year study period, and increased slightly in older men (60-79 years). In simulations, assumed relative risks for all users of 2.0 for an induction time of up to 15 years, 1.5 for up to 10 years, and 1.2 for up to 5 years were incompatible with observed incidence time trends. For heavy users of mobile phones, risks of 2.0 for up to 5 years' induction were also incompatible. Conclusions: No clear trend change in glioma incidence rates was observed. Several of the risk increases seen in case-control studies appear to be incompatible with the observed lack of incidence rate increase in middle-aged men. This suggests longer induction periods than currently investigated, lower risks than reported from some case-control studies, or the absence of any association. Copyright © 2012 by Lippincott Williams & Wilkins.


Jaakkola S.,University of Helsinki | Lyytinen H.K.,University of Helsinki | Pukkala E.,Institute for Statistical and Epidemiological Cancer Research | Ylikorkala O.,University of Helsinki
Gynecologic Oncology | Year: 2011

Objective: Insufficient data exist on the effect of postmenopausal hormone therapy as the risk factor for uterine sarcomas. We therefore evaluated the association of estradiol-progestin therapy (EPT) with the risk of uterine sarcoma in nation-wide cohort study. Methods: All Finnish women (> 50 years of age) who had used EPT during the years 1994-2008 for at least 6 months (n = 243,857) were identified from the national Medical Reimbursement Registry. Their incidence of uterine stromal and leiomyosarcoma among the EPT users was compared to that in the background population with the aid of the Finnish Cancer Registry. Results: A total of 76 uterine sarcomas were encountered in the EPT cohort; 45 (59%) were leiomyosarcomas, 24 (32%) stromal sarcomas and 7 (9%) other sarcomas. The exposure to EPT for less than 5 years did not associate with significant rises in the sarcoma risk but longer exposure was accompanied with significant risk elevations for all uterine sarcomas: the standardized incidence ratio (SIR) for 5-10 years of use was 2.0, 95% confidence interval (CI) 1.4-2.9 and for 10 years of use 3.0 (1.3-5.9): the SIRs were highest for leiomyosarcoma. The sequential and continuous uses of progestin were associated with similar increased SIRs for uterine sarcoma. Conclusions: The use of EPT for 5 years or more is associated with an increased risk for uterine sarcomas. This turns to an absolute excess risk of 2-3 extra uterine sarcoma cases per 10,000 long-time EPT users followed for 10 years. © 2011 Elsevier Inc.


Lyytinen H.K.,University of Helsinki | Dyba T.,Institute for Statistical and Epidemiological Cancer Research | Ylikorkala O.,University of Helsinki | Pukkala E.I.,Institute for Statistical and Epidemiological Cancer Research | Pukkala E.I.,University of Tampere
International Journal of Cancer | Year: 2010

The purpose of this study was to evaluate the association between postmenopausal hormone therapy (HT) and the risk for breast cancer in recently postmenopausal Finnish women. All Finnish women with first invasive breast cancer diagnosed between the ages of 50 and 62 years during 1995-2007 (n = 9,956) were identified from the Finnish Cancer Registry. For each case, 3 controls of the same age were retrieved from the Finnish Population Register. The cases and controls were linked to the national medical reimbursement register to assess the use of HT. The odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer were calculated with conditional logistic regression analysis, adjusting for parity, age at the first birth and health care district. Estradiol-only therapy (991 users with breast cancer, n) or oral progestagen (n = 138) was not accompanied by an increased risk. Estradiol-progestagen therapy (EPT) (n = 1,731) was associated with an elevated risk in the whole series (OR 1.36; 95% CI 1.27-1.46). The risk became detectable in less than 3 years of use. Continuous EPT use tended to be associated with a higher risk for breast cancer than the sequential EPT use. The use of tibolone (n = 80) (1.36; 1.15-1.96), a levonorgestrel-releasing intrauterine system (LNG-IUS) alone (n = 154) (1.45; 1.97-1.77) or as a complement to estradiol (n = 137) (2.15; 1.72-2.68) was also associated with an increased risk. The association between HT use and the risk for breast cancer shows a large variation between various forms of HT, and also the use of LNG-IUS may carry a risk. © 2009 UICC.


Jaakkola S.,University of Helsinki | Lyytinen H.K.,University of Helsinki | Dyba T.,Institute for Statistical and Epidemiological Cancer Research | Ylikorkala O.,University of Helsinki | Pukkala E.,Institute for Statistical and Epidemiological Cancer Research
International Journal of Cancer | Year: 2011

This study evaluates the effect of different modes of estradiol-progestagen therapy (EPT) regimens on the postmenopausal endometrial cancer risk in Finland. Women diagnosed with endometrial cancer in 1995-2007 at the age of 50-80 years were identified from the Finnish Cancer Registry (N = 7,261). For each case, three age-matched controls were retrieved from the Finnish Population Register. The use of EPT since 1994 was ascertained from the national Medical Reimbursement Register. Odds ratios (ORs) for different EPT regimens were calculated with conditional logistic regression analysis, adjusted for parity and ages at the deliveries. For use of <5 years, the OR for sequential EPT was 0.67 (95% confidence interval 0.52-0.86), for continuous EPT 0.45 (0.27-0.73), and for estradiol plus levonorgestrel-releasing intrauterine device system (LNG-IUS) 0.39 (0.17-0.88). A decreased risk persisted for the use of continuous EPT and estradiol plus LNG-IUS of up to 10 years. The use of long-cycle EPT showed a tendency toward an elevated risk both for exposure of <5 years (1.40; 0.82-2.38) and for estimated use of >5 years (1.63; 1.12-2.38). For an estimated exposure of >10 years, the risk for endometrial cancer was elevated for both users of long-cycle EPT (2.95; 2.40-3.62) and sequential EPT (1.38; 1.15-1.66). Norethisterone acetate and medroxyprogesterone acetate as parts of EPT did not differ in their endometrial cancer risk. The use of tibolone showed no endometrial risk. The use of sequential and long-cycle EPT is associated with an increased risk of endometrial cancer, whereas the use of continuous EPT or estradiol plus LNG-IUS shows a decreased risk. Copyright © 2011 UICC.


Huvinen M.,Outokumpu | Pukkala E.,Institute for Statistical and Epidemiological Cancer Research | Pukkala E.,University of Tampere
BMJ Open | Year: 2013

Objectives: The aim of the study was to assess the risk of cancer among workers employed in the Finnish ferrochromium and stainless steel industry since the beginning of production in 1967. Methods: The study cohort was made up of all persons employed by the Finnish stainless steel production chain from chromite mining to cold rolling of stainless steel during the period 1967-2004, and it was divided into subcohorts by production units with specific exposure patterns of the subcohorts assessed in previous studies. Follow-up for cancer through the files of the Finnish Cancer Registry was performed using the personal identity code as key. Standardised incidence ratios (SIRs) were calculated as the ratios of observed numbers of cancer cases and numbers expected on the basis of incidence rates in the population of the same region. Results: The overall cancer incidence was at the expected level. The lung cancer risk was decreased in the whole cohort (SIR 0.79;95% CI 0.65 to 1.08). The incidence of prostate cancer was significantly increased (1.31;1.05 to 1.61) and that for kidney cancer was significantly decreased (0.38;0.14 to 0.82). None of the department-specific SIRs for lung cancer were significantly different from 1.0. No cancers of the nose and nasal sinuses were observed among workers in the ferrochromium smelter or the stainless steel melting shop. Conclusions: It is not likely that the occupational exposures in the Finnish ferrochromium and stainless steel industry would have increased the risk of cancer.


Huvinen M.,Outokumpu | Pukkala E.,Institute for Statistical and Epidemiological Cancer Research | Pukkala E.,University of Tampere
Occupational Medicine | Year: 2016

Background: Although stainless steel has been produced for more than a hundred years, exposure-related mortality data for production workers are limited. Aims: To describe cause-specific mortality in Finnish ferrochromium and stainless steel workers.Methods: We studied Finnish stainless steel production chain workers employed between 1967 and 2004, from chromite mining to cold rolling of stainless steel, divided into sub-cohorts by production units with specific exposure patterns. We obtained causes of death for the years 1971-2012 from Statistics Finland. We calculated standardized mortality ratios (SMRs) as ratios of observed and expected numbers of deaths based on population mortality rates of the same region. Results: Among 8088 workers studied, overall mortality was significantly decreased (SMR 0.77; 95% confidence interval [CI] 0.70-0.84), largely due to low mortality from diseases of the circulatory system (SMR 0.71; 95% CI 0.61-0.81). In chromite mine, stainless steel melting shop and metallurgical laboratory workers, the SMR for circulatory disease was below 0.4 (SMR 0.33; 95% CI 0.07-0.95, SMR 0.22; 95% CI 0.05-0.65 and SMR 0.16; 95% CI 0.00-0.90, respectively). Mortality from accidents (SMR 0.84; 95% CI 0.67-1.04) and suicides (SMR 0.72; 95% CI 0.56-0.91) was also lower than in the reference population. Conclusions: Working in the Finnish ferrochromium and stainless steel industry appears not to be associated with increased mortality. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine.


Jansen L.,German Cancer Research Center | Hakulinen T.,Institute for Statistical and Epidemiological Cancer Research | Brenner H.,German Cancer Research Center
British Journal of Cancer | Year: 2013

Background: Period analysis is increasingly used to compute long-term cancer survival, as it provides better prediction of survival of newly diagnosed patients than traditional cohort analysis. However, the patient population to which period survival estimates best pertain to and which should be described in a study is less obvious. Methods: Using Finnish Cancer Registry data on 23 common cancer sites, age-standardized period estimates of 5-, 10-, 15-, and 20-year relative survival were computed for each 2-, 5-, and 10-year calendar period in 1954-2003 and compared with survival estimates for two cohorts by means of mean, mean absolute and mean squared differences: a full cohort of all patients potentially contributing some data to the survival analysis and a restricted cohort of patients diagnosed in the period of interest. Results: In most computations, survival estimates for the full cohorts were on average closer to the period estimates for the majority of cancer sites. For 10-year survival, results were less obvious with respect to the mean difference. However, mean squared and mean absolute differences were smaller for the majority of cancers when using the full cohort. Conclusion: Our results suggest that the full cohort should be described in reports of period survival analysis. © 2013 Cancer Research UK. All rights reserved.


Seppa K.,Institute for Statistical and Epidemiological Cancer Research | Seppa K.,University of Oulu | Hakulinen T.,Institute for Statistical and Epidemiological Cancer Research | Laara E.,University of Oulu
British Journal of Cancer | Year: 2012

Background: Random error in the numbers of avoidable deaths among cancer patients has not been considered in earlier studies. Methods: Methods to obtain valid confidence intervals (CIs) for numbers of avoidable deaths were developed. The excess mortality rates were estimated for patients diagnosed with colon cancer in five cancer control regions in Finland during 2000-2007 using a relative survival regression model. Numbers of avoidable deaths due to colon cancer and other causes, respectively, were estimated in different scenarios. Results: Altogether, 4139 and 1335 out of 10 772 patients under 90 years at diagnosis were estimated to have died due to colon cancer and other causes, respectively, during the first 5 years after diagnosis. If all the patients had shared the relative survival of the largest cancer control region to which the country capital belongs, the estimated number of avoidable deaths would have been 146 (95% CI 3-290). Conclusion: Random error in numbers of avoidable deaths, often substantial, can be quantified by realistic error margins, based on appropriate statistical methods. © 2012 Cancer Research UK.


Pukkala E.,Institute for Statistical and Epidemiological Cancer Research
Methods in molecular biology (Clifton, N.J.) | Year: 2011

The Nordic countries have a long tradition of register-based epidemiologic studies. Numerous population-based specialized registers offer high-quality data from individuals, and the extensive use of register data further improves the quality of the registers. Unique personal identity codes given to every resident and used in all registers guarantee easy and accurate record linkage. A legislation that makes the use of the existing data possible for purposes that benefit both registered individuals and the society - instead of forcing researchers to use their energy in repeated questionnaire studies, disturbing individuals' privacy and leading to response and recall biases - is a prerequisite for effective epidemiologic research. Biobanks can be considered an additional type of registers. They may offer data from individuals that cannot be reliably collected via questionnaire surveys. In turn, other types of registers are crucial in biobank-based studies (1) in defining for how long the persons in biobank cohorts are at risk of getting the diseases, (2) to get information on cofactors that may modify the relative risk measured by the biomarkers, and (3) to get information on the long-term outcome events. This chapter describes the possibilities of register use mainly in Finland - a typical representative of the Nordic "paradise of register-based epidemiological research" - in research of cancer etiology. The ongoing Nordic research project Changing work life and cancer risk in the Nordic countries (NOCCA) will be described as an example of a massive register use, including both direct linkages on an individual level and indirect group level linkages.

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