Risk factors, epidemiology and prognosis of cholangiocarcinoma in Finland

Background: Cholangiocarcinoma (CCA) is a cancer arising from the intra- and extrahepatic bile ducts. The early stages are often asymptomatic, CCA is frequently diagnosed in an advanced stage and the prognosis of CCA is often dismal. Objective: Our objective was to estimate the incidence of CCA in Finland and to identify risk factors for CCA, with a special interest in primary sclerosing cholangitis (PSC). Methods: We identified all CCA cases during 1974-2018 from the Finnish Cancer Registry and calculated age-standardised incidence rates. Five controls for each case were extracted from the Population Registry, matched by age, gender and municipality of residence at the time of diagnosis. Odds ratios (ORs) for risk factors were estimated with conditional logistic regression and survival estimates with the Kaplan-Meier method. Results: Incidence of CCA remained stable in both genders; the age-standardised rate (World Standard) in 2013-2017 in males and females was 1.7 per 100,000 person years and 1.3 per 100,000 person years, respectively. Primary sclerosing cholangitis carried a 30-fold risk of intrahepatic cholangiocarcinoma (iCCA) and 25-fold risk of extrahepatic cholangiocarcinoma (eCCA). Diabetes, inflammatory bowel disease and liver cirrhosis were associated with iCCA, whereas cholelithiasis and viral hepatitis C were associated with eCCA. The cumulative 5-year survival was 4.6%. Conclusions: The incidence of CCA has been stable. Known risk factors for CCA were confirmed, with PSC having the highest OR. Survival remains poor.Peer reviewe

Groundwater radon exposure and risk of lung cancer: A population-based study in Finland

Naturally occurring radioactive elements can be found in groundwater and exposure to such elements is associated with an increased risk of lung cancer. In this study, we aimed to observe the association between exposure to these radioactive elements in groundwater and the risk of lung cancer in selected regions in Finland. This is a population-based study from 1955 to 2019 in Finland. The exposed municipalities with their corresponding hospital districts were selected based on radon measurements at groundwater treatment plants. Lung cancer cases were obtained from the Finnish cancer registry. The 5-year incidence rates for lung cancer were calculated and a comparison was made between each of the hospital districts with radon exposure. More than 93,000 cases of lung cancer were reported in the radon-exposed regions over the examined period of 64 years. The highest number of cases was recorded in the Helsinki University hospital district and the least in the Southern Savo hospital district. Similarly, the lung cancer incidence rate was highest in Lapland and lowest in the Southern Savo hospital district. The number of daily smokers in the working-age population appears to have decreased in all the hospital districts from 2013 to 2018. A statistically significant increased risk of lung cancer was observed in the high radon-exposed hospital districts compared to those with lower exposure. Groundwater radon exposure is observed to be associated with an increased risk of lung cancer

Surviving & Thriving; a healthy lifestyle app for new US firefighters: usability and pilot study protocol

In the United States (US), new firefighters’ fitness and health behaviors deteriorate rapidly after fire academy graduation. Over the long-term, this increases their risks for chronic diseases. This study protocol describes the proposed usability testing and pilot study of a newly designed and developed healthy lifestyle smartphone app, “Surviving & Thriving”, tailored towards young US firefighters. “Surviving & Thriving” will provide interactive educational content on four lifestyle factors; nutrition, sleep, physical activity, and resilience, and include a personalized journey, habit tracker, and elements of gamification to promote engagement and long-term healthy behavior change. The first phase of the app development entails alpha testing by the research team and pre-beta testing by a fire service expert panel which will help refine the app into a pre-consumer version. Upon completion of the full app prototype, beta ‘usability’ testing will be conducted among new fire academy graduates from two New England fire academies to collect qualitative and quantitative feedback via focus groups and satisfaction surveys, respectively. A last phase of piloting the app will evaluate the app’s efficacy at maintaining/improving healthy lifestyle behaviors, mental health metrics, and physical fitness metrics. We will also evaluate whether firefighters’ perceived “health cultures” scores (ratings of each fire station’s/fire department’s environments as to encouraging/discouraging healthy behaviors) modify the changes in health metrics after utilizing the app for three to six months. This novel user-friendly app seeks to help new firefighters maintain/improve their health and fitness more effectively, reducing their risk of lifestyle-related chronic disease. Firefighters who can establish healthy habits early in their careers are more likely to sustain them throughout their lives

Life expectancy and disease burden in the Nordic countries : results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background The Nordic countries have commonalities in gender equality, economy, welfare, and health care, but differ in culture and lifestyle, which might create country-wise health differences. This study compared life expectancy, disease burden, and risk factors in the Nordic region. Methods Life expectancy in years and age-standardised rates of overall, cause-specific, and risk factor-specific estimates of disability-adjusted life-years (DALYs) were analysed in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Data were extracted for Denmark, Finland, Iceland, Norway, and Sweden (ie, the Nordic countries), and Greenland, an autonomous area of Denmark. Estimates were compared with global, high-income region, and Nordic regional estimates, including Greenland. Findings All Nordic countries exceeded the global life expectancy; in 2017, the highest life expectancy was in Iceland among females (85.9 years [95% uncertainty interval [UI] 85.5-86.4] vs 75.6 years [75.3-75.9] globally) and Sweden among males (80.8 years [80.2-81.4] vs 70.5 years [70.1-70.8] globally). Females (82.7 years [81.9-83.4]) and males (78.8 years [78.1-79.5]) in Denmark and males in Finland (78.6 years [77.8-79.2]) had lower life expectancy than in the other Nordic countries. The lowest life expectancy in the Nordic region was in Greenland (females 77.2 years [76.2-78.0], males 70.8 years [70.3-71.4]). Overall disease burden was lower in the Nordic countries than globally, with the lowest age-standardised DALY rates among Swedish males (18 555.7 DALYs [95% UI 15 968.6-21 426.8] per 100 000 population vs 35 834.3 DALYs [33 218.2-38 740.7] globally) and Icelandic females (16 074.1 DALYs [13 216.4-19 240.8] vs 29 934.6 DALYs [26 981.9-33 211.2] globally). Greenland had substantially higher DALY rates (26 666.6 DALYs [23 478.4-30 218.8] among females, 33 101.3 DALYs [30 182.3-36 218.6] among males) than the Nordic countries. Country variation was primarily due to differences in causes that largely contributed to DALYs through mortality, such as ischaemic heart disease. These causes dominated male disease burden, whereas non-fatal causes such as low back pain were important for female disease burden. Smoking and metabolic risk factors were high-ranking risk factors across all countries. DALYs attributable to alcohol use and smoking were particularly high among the Danes, as was alcohol use among Finnish males. Interpretation Risk factor differences might drive differences in life expectancy and disease burden that merit attention also in high-income settings such as the Nordic countries. Special attention should be given to the high disease burden in Greenland. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Faster than Nyquist signaling and analysis of Its performance under uncoded/coded transmission systems

The future demand of increased transmission rate and bandwidth efficiency is of prime concern in the modern wireless communication systems. Faster than Nyquist signaling (FTN) is under the great interest of research to address this issue of high data rate, which is also a major requirement, for the fifth generation (5G) communication networks. The data bits are transmitted at a rate higher than the conventional methods which are bounded by the Nyquist condition and the outputs are compared so as to analyze the benefits. Receiver processing techniques are implemented to achieve the high data rate with improved error performance at the lower decoding complexity. Considering the bandwidth efficiency as a key factor, more data symbols are sent at the given time interval by reducing the time period for signal transmission. This ensures more data being transmitted. In the scenario of perfect Nyquist signaling, pulse designs were based on the principle of orthogonality. The signal pulse form h(t) is orthogonal with respect to shifts by nT, where T is the signaling interval. In the thesis, the time period is reduced to T < 1, which prompt more symbols to be transmitted. The pulses are no longer orthogonal. These non orthogonal FTN signals are accepted as a promising approach for the required solution of increased data rate. FTN comes as a tradeoff between the high data rate achievement and error probability. Reduction of the time factor affirms good data rate but at the same time, cost of high error rate has to be paid. Efficient receiver processing techniques are designed to compensate between these two factors. Main obstacle due to the reduction of time period in FTN signaling is to tackle the unavoidable inter symbol interferences (ISI). Going beyond the Nyquist bound, as a consequence, results high ISI. This necessitates an effective receiver processing to overcome the ISI. Minimum mean square error (MMSE) detection algorithm is employed to equalize the received signals and analyze the performance of the FTN system. Finally, the system portrayal is studied by processing the results under the implementation of turbo coding systems. The bit error rate (BER) characteristics are analyzed under these circumstances. Efficient encoding pattern and decoding algorithm helps in reducing the errors. Analysis of the simulation results show that the turbo code proficiency is improved by increasing the number of iterations. Performance indication is also related to the frame size or the interleaver size and the signal power. In other words, it comes as a trade-off between energy efficiency, bandwidth efficiency, complexity and error rates. Furthermore, for the fair comparison of the performance analysis, transmission rates for turbo coded transmission systems under the conditions of Nyquist signaling and FTN signaling are made equivalent

Työperäiset altistukset ja virtsarakon syövän riski : Väestötutkimukset Pohjoismaista ja Kanadasta

Virtsarakko on virtsateiden osa, joka kerää ja säilöö virtsaa munuaisista. Siinä on useita kerroksia. Virtsarakon syöpä alkaa useimmiten sisimmästä kerroksesta. Yleisin virtsarakon syöpätyyppi on uroteelin karsinooma. Virtsarakon syöpä on yleisempää miehillä kuin naisilla ja se ilmenee yleisimmin yli 60-vuotiaana. Se on yhdeksänneksi yleisin syöpätyyppi maailmanlaajuisesti. Ammattiin liittyvät tekijät on tunnistettu sen merkittävimmäksi riskitekijäksi tupakoinnin jälkeen. On arvioitu, että työperäinen altistus saattaa olla syynä jopa viidennekseen kaikista virtsarakon syöpätapauksista teollistuneissa maissa, mutta tutkimusten tulokset ovat olleet epäjohdonmukaisia. Tämän tutkimuksen tarkoitus oli arvioida työhön liittyvien tekijöiden ja virtsarakon syövän riskin yhteyttä. Tämä tutkimus perustuu Nordic Occupational Cancer (NOCCA) -aineistoon ja Canadian Census Health and Environment Cohort (CanCHEC) -aineistoon. NOCCA käsittää Tanskan, Suomen, Islannin, Ruotsin ja Norjan koko työikäiset väestöt, jotka osallistuivat yhteen tai useampaan väestönlaskentaan vuonna 1960, 1970, 1980/1981 ja/tai 1990, yhteensä 15 miljoonaa henkilöä. Seurantatutkimus aloitettiin varhaisimmasta väestökyselystä ja se jatkui vuoteen 2005 saakka. Väestönlaskentarekistereistä saatiin demografiset taustamuuttujatiedot, kuten työhistoria, ja nämä rekisterit yhdistettiin kansallisiin syöpätietokantoihin kussakin Pohjoismaassa hyödyntäen henkilöturvatunnuksia. Vastaavasti CanCHEC-aineisto saatiin vuoden 1991 Kanadan väestölaskennan ja kuolleisuusrekisterin (1991-2011) yhdistetyistä aineistoista sekä veroyhteenvetotiedostoista (1984-2001). Kansallisesti edustavaan kohorttiin kuului 2.7 miljoonaa henkilöä, joiden ikä oli 25-74 vuotta väestölaskentapäivänä 4. kesäkuuta 1991. CanCHEC sisältää tietoa demografisista ja sosioekonomisista tekijöistä, asuinpaikasta, syövistä sekä kuolleisuudesta Kanadan väestössä yli 20 vuoden ajalta. Osatutkimusta I varten pohjoismaisten väestöjen ja niissä tavattujen 148,669 virtsarakon syöpädiagnoosiin saaneen työnimikkeet jaoteltiin 53 kategoriaan. Vakioidut ilmaantuvuussuhteet (standardised incidence ratio, SIR) arvioitiin näille kategorioille. Virtsarakkosyövän riski oli huomattavasti väestön keskiarvoa suurempi tupakkateollisuuden työntekijöillä SIR 1.57 (95 prosentinluottamusväli [confidence interval], CI 1.24-1.96), nuohoojilla SIR 1.48 (95% CI 1.16-1.30), tarjoilijoilla SIR 1.43 (95% CI 1.33-1.53), kampaajilla SIR 1.28 (95% CI 1.18-1.40), merimiehillä SIR 1.22 (95% CI 1.16-1.30), painotyöntekijöillä SIR 1.21 (95% CI 1.14-1.30) ja LVI-asentajilla SIR 1.20 (95% CI 1.13-1.30). Vähemmän mutta edelleen tilastollisesti merkitsevästi kohonneen riskin työntekijöihin kuuluivat myyntityöntekijät, juomateollisuustyöntekijät, kuljettajat, pesulatyöntekijät, maalarit sekä valimotyöntekijät. Väestökeskiarvoa selvästi pienempiä riskejä havaittiin maanviljelijöillä SIR 0.70 (95% CI 0.68-0.71), metsätyöntekijöillä SIR 0.74 (95% CI 0.70-0.78) ja puutarhureilla SIR 0.78 (95% CI 0.75-0.80). Osatutkimus II vertasi korkean ja matalan riskin ammattikategorioiden samankaltaisuutta Pohjoismaissa ja Kanadassa. Vertailukelpoisuuden vuoksi NOCCA-tulokset rajattiin samaan ajanjaksoon Kanadan tutkimuksen kanssa. CanCHEC-tutkimuksen osalta virtsarakon syövän riskitiheyssuhteet (hazard ratio, HR) laskettiin 42 ammattikategorialle. Seurantajakson ajalta NOCCA-aineistossa havaittiin yhteensä 73,653 syöpätapausta ja CanCHEC-aineistossa 8,170 syöpätapausta. Molemmissa aineistossa samalla tavalla kohonnut riski havaittiin vain myyntityöntekijöillä. Opettajilla ja maataloustyöntekijöillä oli molemmissa kohorteissa alentunut virtsarakon syövän riski. Osatutkimus III hyödynsi NOCCA-aineiston miehillä esiintyneiden keuhko- ja virtsarakon syöpätapausten tietoja yllämainituissa 53 ammattikategoriassa. Tämä tutkimus hyödynsi 111,485 virtsarakon syöpä- ja 208,297 keuhkosyöpätapauksen tietoja. Keuhkosyöpätapausten SIR-lukua käytettiin sijaismuuttujana tupakoinnin yleisyydelle kussakin ammatissa. Kun virtsarakkosyövän SIR-luvut vakioitiin tupakoinnin sijaismuuttujalla, SIR-luvut kaikissa ammateissa olivat lähempänä ykköstä kuin tupakointivakioimattomat SIR-luvut. Vakioinnin jälkeen jäljelle jäi kuitenkin muutamia korkean riskin ammatteja, mikä viittaa siihen, että kyseisessä ammatissa työskentelevillä on muitakin rakkosyövän riskiä nostavia tekijöitä kuin tupakointi. Näihin ammatteihin kuuluvat nuohoojat (tupakointivakioitu SIR 1.29 (95% CI 1.05-1.56), tarjoilijat SIR 1.22 (95% CI 1.07-1.38), kampaajat SIR 1.14 (95% CI 1.02-1.26), kokit SIR 1.12 (95% CI 1.01-1.25) sekä kirjapainotyöntekijät SIR 1.11 (95% CI 1.04-1.18). Osatutkimus IV arvioi liuotinaltistusten ja virtsarakon syövän riskin yhteyttä neljässä Pohjoismaassa (poisluettuna Tanska). Tämä tutkimus sisälsi 113,343 virtsarakon syöpätapausta ja 566,715 verrokkia, jotka oli kaltaistettu asuinmaan, sukupuolen ja syntymävuoden mukaan. Syöpätapausten ja verrokkien väestökyselyyn perustuvat työnimikkeet linkitettiin työaltistusmatriisiin (Job Exposure Matrix, JEM), joka oli luotu NOCCA-tutkimuksen yhteydessä kumulatiivisten altistusmäärien arvioimiseksi (NOCCA-JEM). Riskitiheyssuhteet kullekin liuotinaineelle eritasoisesti altistuneille verrattuna altistumattomiin arvioitiin käyttäen logistista regressioanalyysia. Tutkimuksessa havaittiin lisääntynyt riski korkean tason altistumiselle trikloorietyleenille HR 1.23 (95% CI 1.12-1.40), tolueenille HR 1.20 (95% CI 1.00-1.38), bentseenille HR 1.16 (95% CI 1.04-1.31), aromaattisille hiilivetyliuottimille HR 1.10 (95% CI 0.94-1.30) sekä alifaattisille ja alisyklisille hiilivetyliuottimille HR 1.08 (95% CI 1.00-1.23), ja lisäksi keskitason altistumiselle tetrakloorietyleenille HR 1.12 (95% CI 1.02-1.23). Yllä esitettyjen tulosten perusteella tämä tutkimus tukee näkemystä, jonka mukaan ammatti on yhteydessä virtsarakon syövän riskiin mutta tupakointi on tärkein riskitekijä. Esimerkiksi liuotinaltisteilla näytti olevan merkittävä rooli. NOCCA on maailman suurin ammattikohtaista syöpäriskiä tarkasteleva tutkimus ja CanCHEC puolestaan suurin kanadalainen vastaavanlainen tutkimus. Suuri määrä virtsarakon syöpätapauksia yhdistettynä vuosikymmenien taakse ulottuviin työhistoriatietoihin sekä työaltistusmatriisin käyttö altistekohtaisten määrällisten altistusten arvioimiseksi ovat tämän väitöskirjatutkimuksen laadun merkittäviä kulmakiviä.Bladder is the part of urinary system that collects and stores urine from kidneys. It has several layers, and bladder cancer usually starts in the innermost layer. The most common type is transitional cell carcinoma. Bladder cancer is more common in men than women, and its rate usually arises after the age of 60 years. It is the ninth most common incident cancer worldwide. Occupation-related factors have been identified as its most important risk factor after smoking. It has been estimated that occupational exposure could account for as much as 20% of all bladder cancer cases in industrialised countries, but studies have shown inconsistent findings. The aim of this study was to assess the association of “work related factors” and risk of bladder cancer. This study was based on the Nordic Occupational Cancer (NOCCA) Study and the Canadian Census Health and Environment Cohort (CanCHEC). NOCCA comprises the working age populations from Denmark, Finland, Iceland, Sweden and Norway who participated in one or more population censuses in 1960, 1970, 1980/1981 and/or 1990, altogether about 15 million individuals. Follow-up started from the earliest census and continued up to 2005. Census records provided information on demographic variables such as employment history, and these records were linked to national cancer registries in each Nordic country through unique personal identity codes. Likewise, CanCHEC was derived from respondents of the 1991 Canadian census who were included in the Canadian Census Mortality and Follow-up study. This study utilised data from the linkage of the 1991 Canadian census with the Canadian mortality database (1991-2011), Canadian Cancer Registry (1992-2010) and historical tax summary files (1984-2001). The nationally representative cohort included about 2.7 million individuals aged 25 to 74 years on the census day (4 June 1991). The CanCHEC comprises information on demographic, socioeconomic, place of residence, cancer and mortality of Canadian population over a period of 20 years. For study I, occupational titles of entire populations and their 148,669 cases of bladder cancer diagnosed from 1961 to 2005 in the Nordic countries were classified into 53 categories, and a group of economically inactive persons. Standardised incidence ratios (SIR) were estimated for these categories. The study identified significantly increased SIRs among tobacco workers SIR 1.57 (95% confidence interval [CI] 1.24-1.96), chimney sweeps SIR 1.48 (95% CI 1.21-1.80), waiters SIR 1.43 (95% CI 1.33-1.53), hairdressers SIR 1.28 (95% CI 1.18-1.40), seamen SIR 1.22 (95% CI 1.16-1.30), printers SIR 1.21 (95% CI 1.14-1.30), and plumbers SIR 1.20 (95% CI 1.13-1.30). Lower but still significantly increased high-risk group included sales workers, beverage workers, drivers, launderers, painters, and smelting workers. Low risks were observed among farmers SIR 0.70 (95% CI 0.68-0.71), forestry workers SIR 0.74 (95% CI 0.70-0.78), and gardeners SIR 0.78 (95% CI 0.75-0.80). Study II compared the similarity of high and low risk occupational categories in the Nordic countries and Canada. For consistency between the studies, NOCCA results were restricted to the period from 1991 to 2005. In CanCHEC, hazard ratios (HR) for bladder cancer were calculated for 42 occupational categories. During the follow up period, altogether 73,653 cases were observed from NOCCA and 8,170 cases from CanCHEC. A consistently increased risk in both data sets was shown only among sales workers. Teachers and agricultural workers had reduced risk of bladder cancer in both cohorts. Study III utilised NOCCA information on both lung and bladder cancer cases in males for 53 occupational categories as mentioned above. This study utilised data on 111,458 cases of bladder and 208,297 lung cancer cases. The SIR of lung cancer was used as a proxy for smoking prevalence. After proxy smoking adjustment, the SIRs in all occupations were closer to unity. However, there were some occupations with high risk even after adjustment, suggesting that there are some other risk factors in addition to smoking. Such occupations include chimney sweeps SIR 1.29 (95% CI 1.05-1.56), waiters SIR 1.22 (95% CI 1.07-1.38), hairdressers SIR 1.14 (95% CI 1.02-1.26), cooks and stewards SIR 1.12 (95% CI 1.01-1.25), and printers SIR 1.11 (95% CI 1.04-1.18). Study IV assessed the association between exposure to solvents and risk of bladder cancer in four Nordic countries (Denmark excluded). This study included 113,343 cases of bladder cancer and 566,715 population controls matched according to the country, sex and birth year. “Census based occupational titles” of the cases and controls were linked with the Job Exposure Matrix created for the NOCCA study (NOCCA-JEM) to estimate quantitative cumulative exposures. Hazard ratios for each solvent - as compared to no exposure level - were estimated using conditional logistic regression. The study observed increased risk for high exposure level of trichloroethylene HR 1.23 (95% CI 1.12-1.40), toluene HR 1.20 (95% CI 1.00-1.38), benzene HR 1.16 (95% CI 1.04-1.31) and aliphatic and alicyclic hydrocarbon solvents HR 1.08 (95% CI 1.00-1.23), and medium level of perchloroethylene HR 1.12 (95% CI 1.02-1.23). Based on these findings, this study supports the view that occupation is evidently associated with the risk of bladder cancer and smoking is an important risk factor that needs to be taken into account. Workplace carcinogenic exposures such as solvents appeared to play a significant role. NOCCA is the largest occupational cancer incidence study globally and CanCHEC is the largest Canadian cohort to explore the occupational cancer risk. A large number of bladder cancer cases together with accurate registry data information on “decade long occupational history” and use of job exposure matrix to measure “occupation specific quantitative exposure” estimates are important quality cornerstones of this study

Työperäiset altistukset ja virtsarakon syövän riski : Väestötutkimukset Pohjoismaista ja Kanadasta

Virtsarakko on virtsateiden osa, joka kerää ja säilöö virtsaa munuaisista. Siinä on useita kerroksia. Virtsarakon syöpä alkaa useimmiten sisimmästä kerroksesta. Yleisin virtsarakon syöpätyyppi on uroteelin karsinooma. Virtsarakon syöpä on yleisempää miehillä kuin naisilla ja se ilmenee yleisimmin yli 60-vuotiaana. Se on yhdeksänneksi yleisin syöpätyyppi maailmanlaajuisesti. Ammattiin liittyvät tekijät on tunnistettu sen merkittävimmäksi riskitekijäksi tupakoinnin jälkeen. On arvioitu, että työperäinen altistus saattaa olla syynä jopa viidennekseen kaikista virtsarakon syöpätapauksista teollistuneissa maissa, mutta tutkimusten tulokset ovat olleet epäjohdonmukaisia. Tämän tutkimuksen tarkoitus oli arvioida työhön liittyvien tekijöiden ja virtsarakon syövän riskin yhteyttä. Tämä tutkimus perustuu Nordic Occupational Cancer (NOCCA) -aineistoon ja Canadian Census Health and Environment Cohort (CanCHEC) -aineistoon. NOCCA käsittää Tanskan, Suomen, Islannin, Ruotsin ja Norjan koko työikäiset väestöt, jotka osallistuivat yhteen tai useampaan väestönlaskentaan vuonna 1960, 1970, 1980/1981 ja/tai 1990, yhteensä 15 miljoonaa henkilöä. Seurantatutkimus aloitettiin varhaisimmasta väestökyselystä ja se jatkui vuoteen 2005 saakka. Väestönlaskentarekistereistä saatiin demografiset taustamuuttujatiedot, kuten työhistoria, ja nämä rekisterit yhdistettiin kansallisiin syöpätietokantoihin kussakin Pohjoismaassa hyödyntäen henkilöturvatunnuksia. Vastaavasti CanCHEC-aineisto saatiin vuoden 1991 Kanadan väestölaskennan ja kuolleisuusrekisterin (1991-2011) yhdistetyistä aineistoista sekä veroyhteenvetotiedostoista (1984-2001). Kansallisesti edustavaan kohorttiin kuului 2.7 miljoonaa henkilöä, joiden ikä oli 25-74 vuotta väestölaskentapäivänä 4. kesäkuuta 1991. CanCHEC sisältää tietoa demografisista ja sosioekonomisista tekijöistä, asuinpaikasta, syövistä sekä kuolleisuudesta Kanadan väestössä yli 20 vuoden ajalta. Osatutkimusta I varten pohjoismaisten väestöjen ja niissä tavattujen 148,669 virtsarakon syöpädiagnoosiin saaneen työnimikkeet jaoteltiin 53 kategoriaan. Vakioidut ilmaantuvuussuhteet (standardised incidence ratio, SIR) arvioitiin näille kategorioille. Virtsarakkosyövän riski oli huomattavasti väestön keskiarvoa suurempi tupakkateollisuuden työntekijöillä SIR 1.57 (95 prosentinluottamusväli [confidence interval], CI 1.24-1.96), nuohoojilla SIR 1.48 (95% CI 1.16-1.30), tarjoilijoilla SIR 1.43 (95% CI 1.33-1.53), kampaajilla SIR 1.28 (95% CI 1.18-1.40), merimiehillä SIR 1.22 (95% CI 1.16-1.30), painotyöntekijöillä SIR 1.21 (95% CI 1.14-1.30) ja LVI-asentajilla SIR 1.20 (95% CI 1.13-1.30). Vähemmän mutta edelleen tilastollisesti merkitsevästi kohonneen riskin työntekijöihin kuuluivat myyntityöntekijät, juomateollisuustyöntekijät, kuljettajat, pesulatyöntekijät, maalarit sekä valimotyöntekijät. Väestökeskiarvoa selvästi pienempiä riskejä havaittiin maanviljelijöillä SIR 0.70 (95% CI 0.68-0.71), metsätyöntekijöillä SIR 0.74 (95% CI 0.70-0.78) ja puutarhureilla SIR 0.78 (95% CI 0.75-0.80). Osatutkimus II vertasi korkean ja matalan riskin ammattikategorioiden samankaltaisuutta Pohjoismaissa ja Kanadassa. Vertailukelpoisuuden vuoksi NOCCA-tulokset rajattiin samaan ajanjaksoon Kanadan tutkimuksen kanssa. CanCHEC-tutkimuksen osalta virtsarakon syövän riskitiheyssuhteet (hazard ratio, HR) laskettiin 42 ammattikategorialle. Seurantajakson ajalta NOCCA-aineistossa havaittiin yhteensä 73,653 syöpätapausta ja CanCHEC-aineistossa 8,170 syöpätapausta. Molemmissa aineistossa samalla tavalla kohonnut riski havaittiin vain myyntityöntekijöillä. Opettajilla ja maataloustyöntekijöillä oli molemmissa kohorteissa alentunut virtsarakon syövän riski. Osatutkimus III hyödynsi NOCCA-aineiston miehillä esiintyneiden keuhko- ja virtsarakon syöpätapausten tietoja yllämainituissa 53 ammattikategoriassa. Tämä tutkimus hyödynsi 111,485 virtsarakon syöpä- ja 208,297 keuhkosyöpätapauksen tietoja. Keuhkosyöpätapausten SIR-lukua käytettiin sijaismuuttujana tupakoinnin yleisyydelle kussakin ammatissa. Kun virtsarakkosyövän SIR-luvut vakioitiin tupakoinnin sijaismuuttujalla, SIR-luvut kaikissa ammateissa olivat lähempänä ykköstä kuin tupakointivakioimattomat SIR-luvut. Vakioinnin jälkeen jäljelle jäi kuitenkin muutamia korkean riskin ammatteja, mikä viittaa siihen, että kyseisessä ammatissa työskentelevillä on muitakin rakkosyövän riskiä nostavia tekijöitä kuin tupakointi. Näihin ammatteihin kuuluvat nuohoojat (tupakointivakioitu SIR 1.29 (95% CI 1.05-1.56), tarjoilijat SIR 1.22 (95% CI 1.07-1.38), kampaajat SIR 1.14 (95% CI 1.02-1.26), kokit SIR 1.12 (95% CI 1.01-1.25) sekä kirjapainotyöntekijät SIR 1.11 (95% CI 1.04-1.18). Osatutkimus IV arvioi liuotinaltistusten ja virtsarakon syövän riskin yhteyttä neljässä Pohjoismaassa (poisluettuna Tanska). Tämä tutkimus sisälsi 113,343 virtsarakon syöpätapausta ja 566,715 verrokkia, jotka oli kaltaistettu asuinmaan, sukupuolen ja syntymävuoden mukaan. Syöpätapausten ja verrokkien väestökyselyyn perustuvat työnimikkeet linkitettiin työaltistusmatriisiin (Job Exposure Matrix, JEM), joka oli luotu NOCCA-tutkimuksen yhteydessä kumulatiivisten altistusmäärien arvioimiseksi (NOCCA-JEM). Riskitiheyssuhteet kullekin liuotinaineelle eritasoisesti altistuneille verrattuna altistumattomiin arvioitiin käyttäen logistista regressioanalyysia. Tutkimuksessa havaittiin lisääntynyt riski korkean tason altistumiselle trikloorietyleenille HR 1.23 (95% CI 1.12-1.40), tolueenille HR 1.20 (95% CI 1.00-1.38), bentseenille HR 1.16 (95% CI 1.04-1.31), aromaattisille hiilivetyliuottimille HR 1.10 (95% CI 0.94-1.30) sekä alifaattisille ja alisyklisille hiilivetyliuottimille HR 1.08 (95% CI 1.00-1.23), ja lisäksi keskitason altistumiselle tetrakloorietyleenille HR 1.12 (95% CI 1.02-1.23). Yllä esitettyjen tulosten perusteella tämä tutkimus tukee näkemystä, jonka mukaan ammatti on yhteydessä virtsarakon syövän riskiin mutta tupakointi on tärkein riskitekijä. Esimerkiksi liuotinaltisteilla näytti olevan merkittävä rooli. NOCCA on maailman suurin ammattikohtaista syöpäriskiä tarkasteleva tutkimus ja CanCHEC puolestaan suurin kanadalainen vastaavanlainen tutkimus. Suuri määrä virtsarakon syöpätapauksia yhdistettynä vuosikymmenien taakse ulottuviin työhistoriatietoihin sekä työaltistusmatriisin käyttö altistekohtaisten määrällisten altistusten arvioimiseksi ovat tämän väitöskirjatutkimuksen laadun merkittäviä kulmakiviä.Bladder is the part of urinary system that collects and stores urine from kidneys. It has several layers, and bladder cancer usually starts in the innermost layer. The most common type is transitional cell carcinoma. Bladder cancer is more common in men than women, and its rate usually arises after the age of 60 years. It is the ninth most common incident cancer worldwide. Occupation-related factors have been identified as its most important risk factor after smoking. It has been estimated that occupational exposure could account for as much as 20% of all bladder cancer cases in industrialised countries, but studies have shown inconsistent findings. The aim of this study was to assess the association of “work related factors” and risk of bladder cancer. This study was based on the Nordic Occupational Cancer (NOCCA) Study and the Canadian Census Health and Environment Cohort (CanCHEC). NOCCA comprises the working age populations from Denmark, Finland, Iceland, Sweden and Norway who participated in one or more population censuses in 1960, 1970, 1980/1981 and/or 1990, altogether about 15 million individuals. Follow-up started from the earliest census and continued up to 2005. Census records provided information on demographic variables such as employment history, and these records were linked to national cancer registries in each Nordic country through unique personal identity codes. Likewise, CanCHEC was derived from respondents of the 1991 Canadian census who were included in the Canadian Census Mortality and Follow-up study. This study utilised data from the linkage of the 1991 Canadian census with the Canadian mortality database (1991-2011), Canadian Cancer Registry (1992-2010) and historical tax summary files (1984-2001). The nationally representative cohort included about 2.7 million individuals aged 25 to 74 years on the census day (4 June 1991). The CanCHEC comprises information on demographic, socioeconomic, place of residence, cancer and mortality of Canadian population over a period of 20 years. For study I, occupational titles of entire populations and their 148,669 cases of bladder cancer diagnosed from 1961 to 2005 in the Nordic countries were classified into 53 categories, and a group of economically inactive persons. Standardised incidence ratios (SIR) were estimated for these categories. The study identified significantly increased SIRs among tobacco workers SIR 1.57 (95% confidence interval [CI] 1.24-1.96), chimney sweeps SIR 1.48 (95% CI 1.21-1.80), waiters SIR 1.43 (95% CI 1.33-1.53), hairdressers SIR 1.28 (95% CI 1.18-1.40), seamen SIR 1.22 (95% CI 1.16-1.30), printers SIR 1.21 (95% CI 1.14-1.30), and plumbers SIR 1.20 (95% CI 1.13-1.30). Lower but still significantly increased high-risk group included sales workers, beverage workers, drivers, launderers, painters, and smelting workers. Low risks were observed among farmers SIR 0.70 (95% CI 0.68-0.71), forestry workers SIR 0.74 (95% CI 0.70-0.78), and gardeners SIR 0.78 (95% CI 0.75-0.80). Study II compared the similarity of high and low risk occupational categories in the Nordic countries and Canada. For consistency between the studies, NOCCA results were restricted to the period from 1991 to 2005. In CanCHEC, hazard ratios (HR) for bladder cancer were calculated for 42 occupational categories. During the follow up period, altogether 73,653 cases were observed from NOCCA and 8,170 cases from CanCHEC. A consistently increased risk in both data sets was shown only among sales workers. Teachers and agricultural workers had reduced risk of bladder cancer in both cohorts. Study III utilised NOCCA information on both lung and bladder cancer cases in males for 53 occupational categories as mentioned above. This study utilised data on 111,458 cases of bladder and 208,297 lung cancer cases. The SIR of lung cancer was used as a proxy for smoking prevalence. After proxy smoking adjustment, the SIRs in all occupations were closer to unity. However, there were some occupations with high risk even after adjustment, suggesting that there are some other risk factors in addition to smoking. Such occupations include chimney sweeps SIR 1.29 (95% CI 1.05-1.56), waiters SIR 1.22 (95% CI 1.07-1.38), hairdressers SIR 1.14 (95% CI 1.02-1.26), cooks and stewards SIR 1.12 (95% CI 1.01-1.25), and printers SIR 1.11 (95% CI 1.04-1.18). Study IV assessed the association between exposure to solvents and risk of bladder cancer in four Nordic countries (Denmark excluded). This study included 113,343 cases of bladder cancer and 566,715 population controls matched according to the country, sex and birth year. “Census based occupational titles” of the cases and controls were linked with the Job Exposure Matrix created for the NOCCA study (NOCCA-JEM) to estimate quantitative cumulative exposures. Hazard ratios for each solvent - as compared to no exposure level - were estimated using conditional logistic regression. The study observed increased risk for high exposure level of trichloroethylene HR 1.23 (95% CI 1.12-1.40), toluene HR 1.20 (95% CI 1.00-1.38), benzene HR 1.16 (95% CI 1.04-1.31) and aliphatic and alicyclic hydrocarbon solvents HR 1.08 (95% CI 1.00-1.23), and medium level of perchloroethylene HR 1.12 (95% CI 1.02-1.23). Based on these findings, this study supports the view that occupation is evidently associated with the risk of bladder cancer and smoking is an important risk factor that needs to be taken into account. Workplace carcinogenic exposures such as solvents appeared to play a significant role. NOCCA is the largest occupational cancer incidence study globally and CanCHEC is the largest Canadian cohort to explore the occupational cancer risk. A large number of bladder cancer cases together with accurate registry data information on “decade long occupational history” and use of job exposure matrix to measure “occupation specific quantitative exposure” estimates are important quality cornerstones of this study

Risk Factors for Lichen Sclerosus : A Case-Control Study of 43,000 Finnish Women

Objectives Lichen sclerosus (LS) is an inflammatory skin disease probably arising from an interplay of genetics, local irritation, and autoimmune processes. We identified potential risk factors for the disease using data from nationwide Finnish registries. Methods We identified all women diagnosed with LS within specialized health care during 1998-2016 (n = 10,692) and selected 3 age-matched population control women for each case. We calculated odds ratios (ORs) for possible risk factors using conditional logistic regression. Results Dermatological autoimmune conditions were strongly associated with LS (OR = 15.1, 95% confidence interval [CI] = 13.6-16.7 for morphea; OR = 10.3, 95% CI = 5.02-19.0 for lichen planus; OR = 6.86, 95% CI = 5.65-8.33 for alopecia; OR = 2.20, 95% CI = 1.88-2.56 for vitiligo). A diagnosis of Crohn or celiac disease increased the odds of LS (OR = 1.80, 95% CI = 1.71-1.89; OR = 1.49, 95% CI = 1.28-1.73, respectively) as did urge and stress incontinence (OR = 1.79, 95% CI = 1.71-1.87; OR = 1.28, 95% CI = 1.22-1.35, respectively). The odds of LS were lower in women after a diagnosis of type 1 diabetes (OR = 0.43, 95% CI = 0.41-0.45), coronary artery disease (OR = 0.41, 95% CI = 0.38-0.43), and rheumatoid arthritis (OR = 0.38, 95% CI = 0.36-0.41). Parous women had higher odds of LS (OR = 1.11, 95% CI = 1.04-1.17) than nulliparous ones, but increasing number of births decreased the risk. Lichen sclerosus was not associated with socioeconomic status nor the urbanicity level of the place of residence. Conclusions Certain autoimmune diseases and urinary incontinence were associated with LS.Peer reviewe