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STUDY QUESTION Is there an association between premature ovarian insufficiency (POI) and severe autoimmune diseases before and after POI diagnosis? SUMMARY ANSWER Women with POI had at least one hospital-treated autoimmune disorder preceding POI diagnosis 2.6 times more often compared with matched female controls, and a 2- to 3-fold risk for these diseases for several years after POI diagnosis. WHAT IS KNOWN ALREADY It has been suggested that autoimmunity is an important factor in the pathogenesis of POI. Estimations of the prevalence of POI cases with autoimmune origin have ranged from 4% to 50%. STUDY DESIGN, SIZE, DURATION This population-based registry study included 3972 women diagnosed with spontaneous POI between 1988 and 2017 and 15 708 female population controls and used both case–control and cohort analysis. Autoimmune disease diagnoses were evaluated from childhood until the end of the year 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with POI were identified from the reimbursement registry of the Finnish Social Insurance Institution by their right to hormone replacement therapy (HRT). Four female population controls matched by age and municipality of residence were searched for each POI case to form a reference cohort. Women with a history of cancer or bilateral oophorectomy were excluded. Severe autoimmune disorder diagnoses for the years 1970–2017 were identified from the Hospital Discharge Registry. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using binary logistic regression for cases of having any, or one or more, specific autoimmune diseases preceding the index date (the date when reimbursement for HRT was granted for the POI) among women with POI as compared to controls. Standardized incidence ratios (SIR) with 95% CIs for getting diagnosed with an autoimmune disease after the index date in 3-year follow-up periods among women with POI (who did not have these diseases prior to the index date) were also calculated. The expected numbers of autoimmune disease cases were based on the incidence of first-onset severe autoimmune disease among the controls. MAIN RESULTS AND THE ROLE OF CHANCE The prevalence of having at least one severe autoimmune disease in women with POI was 5.6% (n = 233), with an OR of 2.6 (95% CI 2.2, 3.1) when compared to population controls. Women with POI had an increased prevalence of several specific autoimmune diseases prior to the index date compared to controls: polyglandular autoimmune diseases (OR 25.8, 95% CI 9.0, 74.1), Addison's disease (OR 22.9, 95% CI 7.9, 66.1), vasculitis (OR 10.2, 95% 4.3, 24.5), systemic lupus erythematosus (OR 6.3 95% CI 4.2, 20.3), rheumatoid arthritis (OR 2.3, 95% CI 1.7, 3.2), sarcoidosis (OR 2.3, 95% CI 1.2, 4.5), inflammatory bowel diseases (OR 2.2, 95% CI 1.5, 3.3), and hyperthyroidism (OR 1.9, 95% CI 1.2, 3.1); whereas the prevalence of diabetes type 1 and ankylosing spondylitis did not differ between the women with POI and the reference cohort. The SIRs for being diagnosed for the first time with a severe autoimmune disease after POI diagnosis was 2.8 (95% CI 2.3, 3.4), during the first three years after POI diagnosis, decreasing gradually to 1.3 (1.1, 1.6) after 12 years. LIMITATIONS, REASONS FOR CAUTION This study only included autoimmune disorders diagnosed in specialized health care; hence, the overall prevalence of autoimmune disorders in women with POI may be higher. WIDER IMPLICATIONS OF THE FINDINGS Severe autoimmune diseases have a strong association with POI, suggesting that immunological mechanisms play a pivotal role in POI. Future studies should focus on specific autoimmune mechanisms behind POI, from both preventive and curative perspectives. STUDY FUNDING/COMPETING INTEREST(S) This work was financially supported by Oulu University Hospital. S.M.S. received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. H.S. received grants from the Finnish Menopause Society, the Oulu Medical Research Foundation, the Finnish Research Foundation of Gynecology and Obstetrics, UniOGS graduate school, The Finnish Medical Society Duodecim, Orion Research Foundation, and the University of Oulu Scholarship Fund. M.-M.O. received a grant from the Sakari Alhopuro Foundation and the Finnish Diabetes Research Foundation. None of the funders had any involvement in the study design or its execution or reporting. The authors do not have any competing interests to report. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

This article presents the findings of a population-based case-control study on risk factors for lichen planus (LP) in women. The study found that certain conditions such as hepatitis C, oral candidiasis, periodontitis, Sjögren's syndrome, and vitiligo increased the odds of LP, while autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis, and Graves' disease decreased the odds. Cardiometabolic and psychiatric conditions were associated with reduced odds of LP. The study emphasized the importance of considering the temporal order of diagnoses when examining comorbidities and called for further research on the pathogenetic process of LP and its associated conditions. The study did not find any significant association between LP and urbanicity level or socioeconomic status. [Extracted from the article]

STUDY QUESTION Are genetic disorders and congenital malformations associated with premature ovarian insufficiency (POI)? SUMMARY ANSWER A wide range of genetic disorder and congenital malformation diagnoses are associated with POI, especially early onset POI. WHAT IS KNOWN ALREADY POI is known to be associated with some genetic disorders, such as Turner syndrome and Fragile X premutation. Multiple genetic syndromes, such as ataxia teleangiectasia and galactosemia, have also been associated with an increased risk of POI, and many of these genetic syndromes manifest with various congenital malformations. In previous studies, a genetic aetiology has been found for 7–15% of POI cases. STUDY DESIGN, SIZE, DURATION This population-based study included 5011 women diagnosed with POI in 1988–2017. The data were collected from various national registries and covers women with POI nationwide. PARTICIPANTS/MATERIALS, SETTING, METHODS We identified 5011 women diagnosed with POI from 1988 to 2017 from the drug reimbursement registry of the Social Insurance Institution of Finland. Women with surgical POI (bilateral oophorectomy for benign indications) were not included. We selected four population controls per woman with POI matched by month and year of birth and municipality of residence. Diagnostic codes for genetic disorders and congenital malformations (GD/CM) for the cases and controls were searched from the Hospital Discharge Register. Binary logistic regression was used to compare the odds for GD/CM among cases and controls. To minimize bias, for the statistical analyses, we excluded diagnoses which were reported <2 years prior to the index date. MAIN RESULTS AND THE ROLE OF CHANCE Of the women with POI, 15.9% (n = 797) had at least one diagnostic code for GD or CM. The odds ratio (OR) for Turner syndrome was 275 (95% CI 68.1–1110), and for other sex chromosome abnormalities, it was 12.7 (95% CI 4.1–39.1). For autosomal single gene disorders, the OR was 16.5 (95% CI 6.2–43.7). Women with POI had a higher odds of having a GD/CM diagnosis in all categories. The OR for GD/CM diagnoses was highest among the youngest POI patients (10–14 years old, OR 24.1, 95% CI 15.1–38.2). The odds of having POI were higher the more GD or CM diagnoses a woman had. LIMITATIONS, REASONS FOR CAUTION Some women with POI might not have sought help for their symptoms and therefore remain undiagnosed. Due to the register-based nature of our study, we did not have access to more specific genetic diagnoses than international classification of diseases offers. WIDER IMPLICATIONS OF THE FINDINGS GD/CM diagnoses were strongly associated with POI, especially when POI was diagnosed at a young age. The risk of POI was highest in women with multiple GD/CM diagnoses. Early onset POI can be a sign of underlying genetic disorder or congenital anomaly, and this should serve as a reminder for clinicians to consider further examinations. To avoid unnecessary delay in the diagnosis of POI and starting relevant hormone replacement therapy treatment, clinicians should be aware of these associations. STUDY FUNDING/COMPETING INTEREST(S) Oulu University Hospital financially supported this work. H.S. has received personal grants from the Finnish Menopause Society, Oulu Medical Research Foundation, and Finnish Research Foundation of Gynaecology and Obstetrics. S.S. has received grants from the Finnish Menopause Society, the Finnish Medical Foundation, and the Juho Vainio Foundation. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Study Question: What is the incidence of premature ovarian insufficiency (POI), has the incidence of POI changed over time, and what is the risk of POI among relatives of POI women?Summary Answer: The incidence of POI increased among females aged 15-19 years from 2007 onwards and decreased in older age groups, and among relatives of women with POI the risk of POI is significantly increased.What Is Known Already: So far, there has been no good quality, nationwide studies of the incidence of POI. Early menopause has been associated with the elevated risk of early menopause among relatives, but the knowledge of the familial risk of POI is scarce. Lower socioeconomic status has been associated with lower age at natural menopause.Study Design, Size, Duration: Population-based study with 5011 women diagnosed with POI in 1988-2017. The data were collected from national registries and covers POI subjects in entire Finland.Participants/materials, Setting, Methods: Women with hormone replacement therapy reimbursement for POI were identified from Social Insurance Institution (SII). We calculated POI incidence in different age groups and studied the changes in the incidence rate over time in 5-year segments. Four population-based controls were selected from the Digital and Population Data Services Agency (DVV) for each POI woman. Family members of the POI cases and controls were identified from the DVV and linked to SII reimbursement data to identify POI diagnoses among them. The familial risk of POI was estimated with a logistical regression model.Main Results and the Role Of Chance: The incidence was highest in the 35-39 age group, ranging from 73.8/100 000 women-years in 1993-1997 to 39.9/100 000 women-years in 2013-2017. From 2007, the incidence among 15- to 19-year-olds rose from 7.0 to 10.0/100 000 women-years in 2015-2017. Cumulative incidence of POI for women under 40 years in 1988-2017 was 478/100 000 women. The relative risk of POI among relatives of women with POI was 4.6 (95% CI 3.3-6.5) compared to relatives of women without POI. POI women tended to have slightly lower socioeconomic status and level of education compared to controls.Limitations, Reasons For Caution: For some women with POI, diagnosis or reimbursement may be lacking. However, we presume that these women represent a minority due to the nature of the disease and the economic benefits of reimbursement. Some changes in the incidence of POI can reflect changes in clinical practice and changing treatments and reimbursement criteria.Wider Implications Of the Findings: The risk of developing POI is significantly higher in women who have first-degree relatives diagnosed with POI. Raising awareness of the increased risk might lead to earlier diagnosis and initiation of hormonal replacement therapy, possibly preventing adverse effects of low oestrogen levels, such as osteoporosis.Study Funding/competing Interest(s): This work was financially supported by the Oulu University Hospital. H.S. received a grant from Finnish Menopause Society. S.M.S. received a grant from the Finnish Menopause Society, the Finnish Medical Foundation and the Juho Vainio Foundation. The authors do not have any competing interests to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: The aim was to examine the hypothesis that antireflux surgery with fundoplication improves long-term survival compared with antireflux medication in patients with reflux oesophagitis or Barrett's oesophagus. Method: Individuals aged between 18 and 70 years with reflux oesophagitis or Barrett's oesophagus (intestinal metaplasia) documented from in-hospital and specialized outpatient care were selected from national patient registries in Denmark, Finland, Iceland, and Sweden from 1980 to 2014. The study investigated all-cause mortality and disease-specific mortality, comparing patients who had undergone open or laparoscopic antireflux surgery with fundoplication versus those using antireflux medication. Multivariable Cox regression analysis was used to estimate hazard ratios (HRs) with 95 per cent confidence intervals for all-cause mortality and disease-specific mortality, adjusted for sex, age, calendar period, country, and co-morbidity. Results: Some 240 226 patients with reflux oesophagitis or Barrett's oesophagus were included, of whom 33 904 (14.1 percent) underwent antireflux surgery. The risk of all-cause mortality was lower after antireflux surgery than with use of medication (HR 0.61, 95 per cent c.i. 0.58 to 0.63), and lower after laparoscopic (HR 0.56, 0.52 to 0.60) than open (HR 0.80, 0.70 to 0.91) surgery. After antireflux surgery, mortality was decreased from cardiovascular disease (HR 0.58, 0.55 to 0.61), respiratory disease (HR 0.62, 0.57 to 0.66), laryngeal or pharyngeal cancer (HR 0.35, 0.19 to 0.65), and lung cancer (HR 0.67, 0.58 to 0.80), but not from oesophageal cancer (HR 1.05, 0.87 to 1.28), compared with medication, The decreased mortality rates generally remained over time. Conclusion: In patients with reflux oesophagitis or Barrett's oesophagus, antireflux surgery is associated with lower mortality from all causes, cardiovascular disease, respiratory disease, laryngeal or pharyngeal cancer, and lung cancer, but not from oesophageal cancer, compared with antireflux medication. [ABSTRACT FROM AUTHOR]

Summary: Background: The age‐adjusted incidence of cutaneous melanoma (CM) in the Nordic countries has increased during the last 60 years. Few prospective population‐based studies have estimated the occupational variation in CM risk over time. Objectives: To determine occupational variation in CM risk. Methods: A historical prospective cohort study with a 45‐year follow‐up from 1961 to 2005 (Nordic Occupational Cancer Study, NOCCA) based on record linkages between census and cancer registry data for Nordic residents aged 30–64 years in Denmark, Finland, Iceland, Norway and Sweden. National occupational codes were converted to 53 occupational categories, and stratified into indoor, outdoor and mixed work, and into socioeconomic status. The standardized incidence ratios (SIRs) were estimated as observed number of CM cases divided by the expected number calculated from stratum‐specific person‐years and national CM incidence rates. Results: During a follow‐up of 385 million person‐years, 83 898 incident cases of CM were identified. In all countries combined, men with outdoor work had a low SIR of 0·79 [95% confidence interval (CI) 0·77–0·81] and men with indoor work had a high SIR of 1·09 (95% CI 1·07–1·11). Differences in women pointed in the same direction. High socioeconomic status was associated with an excess risk: SIR 1·34 (95% CI 1·28–1·40) in men and SIR 1·31 (95% CI 1·26–1·36) in women. Technical, transport, military and public safety workers with potential skin exposure to carcinogens had excess risks. Conclusions: Occupational variation in CM risk may be partly explained by host, socioeconomic and skin exposure factors. Differences in CM risk across socioeconomic groups attenuated slightly over time. What is already known about this topic?In the Nordic countries, age‐adjusted incidence of cutaneous melanoma (CM) has increased more than four‐fold during the last 60 years.Indoor work and high socioeconomic status have been associated with high CM risk. What does this study add?We determined occupational variation in CM incidence in an all‐Nordic population‐based cohort with 45 years of follow‐up.Excess CM risks were found in selected occupations with potential exposure to skin carcinogens.Differences in CM risk across socioeconomic groups attenuated slightly over follow‐up time. [ABSTRACT FROM AUTHOR]

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Objective: To assess the incidence of lichen sclerosus (LS) in women and the all-cause and cause-specific mortality of women with LS.Design: Population-based descriptive study.Setting: Finland.Population: All Finnish women, including 7790 women diagnosed with LS during the period 1969-2012.Methods: Information gathered from the Finnish Hospital Discharge Register on women with LS was combined with dates and causes of death from Statistics Finland and the Finnish Cancer Registry. Population statistics are from Statistics Finland.Main Outcome Measures: Crude and age-adjusted incidence rates of LS and standardised mortality ratios (SMRs).Results: The incidence rate of LS adjusted for age (European Standard Population) increased from 14 per 100 000 woman-years in 2003 to 22 per 100 000 woman-years in 2010-2012. The age-specific incidence rate was highest in postmenopausal women (24-53 per 100 000) but was also elevated in girls aged 5-9 years (seven per 100 000). The all-cause mortality of women with LS was lower than in the general female population (SMR 0.84, 95% CI 0.78-0.90), mostly as a result of decreased mortality from circulatory diseases (SMR 0.80, 95% CI 0.72-0.89) and dementia and Alzheimer's disease (SMR 0.75, 95% CI 0.62-0.88). The cancer mortality equalled that of the population, but the vulvar cancer mortality was increased (SMR 28.1, 95% CI 19.3-39.4).Conclusions: Lichen sclerosus is a common disease of elderly women. The overall mortality is decreased whereas the mortality as a result of vulvar cancer is increased.Tweetable Abstract: The likelihood of getting LS by age 80 years is 1.6%. The mortality of women with LS is reduced compared with that of the population. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. Methods: We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. Results: Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. Conclusions: Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the cancer risk in a cohort of Finnish patients with systemic lupus erythematosus (SLE) when followed over the long term.Method: The cohort consisted of 182 female and 23 male SLE patients treated at the Helsinki University Central Hospital from 1967 to 1987. The cohort was linked to the Finnish Cancer Registry and followed for cancer incidence from 1967 to 2013. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cases by the number of expected cases for different types of cancer.Results: The mean duration of follow-up was 25.7 years. Forty-five patients out of 205 were diagnosed with cancer, with an increased risk of overall malignancy [SIR 1.90, 95% confidence interval (CI) 1.39-2.54, p < 0.001]. The incidences of soft-tissue sarcoma (SIR 12.1, 95% CI 1.47-43.7, p < 0.05), non-Hodgkin's lymphoma (SIR 12.1, 95% CI 5.82-22.3, p < 0.001), and kidney cancer (SIR 7.79, 95% CI 2.53-18.2, p < 0.01) were significantly elevated.Conclusion: This long-term study confirms that patients with SLE have an increased risk of cancer, particularly non-Hodgkin's lymphoma and kidney cancer. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) and diabetes mellitus (DM) are major health problems. We examined the association between DM and BC stage at diagnosis and subsequent survival in a Finnish cohort of female BC patients. All BC cases (N = 73,170) diagnosed in 1995–2013 with dates and causes of death were identified from the Finnish Cancer Registry. Participation in organized mammography screening was obtained from Mass Inspection Registry. Information on DM diagnoses and background conditions recorded during 1995–2013 were obtained from national Care Register for Health Care and merged to data on medication use from the national Prescription Register. Logistic regression with adjustment for mammography screening and age at BC diagnosis was used to evaluate the risk of advanced stage BC at diagnosis. Cox regression was used to evaluate overall and BC survival. Analyses were adjusted for age, background conditions and mammography screening. Survival analyses were further adjusted for tumor extent, histology and primary treatment. Of the cohort 11,676 (16.0%) had DM. Screening participation did not differ by diabetes. Compared to non‐diabetic women, diabetics had more often locally advanced (odds ratio, OR 1.26; 95% CI 1.18–1.35) or metastatic BC (OR 1.59; 95% CI 1.44–1.75) at diagnosis. During a median follow‐up of 5.8 years after BC diagnosis 10,900 (14.9%) women died of BC. Risk of BC death was higher among diabetic compared to non‐diabetic women (HR 1.36; 95% CI 1.27–1.46). Risk of BC death increased with duration of DM. This supports DM as a risk factor for fatal BC. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence and occupational variation of granulosa cell tumours (GCTs) in Finland, Iceland, Norway and Sweden over a 60-year period, 1953-2012.Design: A longitudinal cohort study.Setting and Population: Finland, Iceland, Norway and Sweden and a total of 249 million women over a 60-year period (1953-2012). The NOCCA (Nordic Occupational Cancer Study) included 6.4 million women with 776 incident GCT cases diagnosed until the end of follow up.Methods: Incidence rates were calculated from the national cancer registries and compared using quasi-Poisson regression models. Occupation-specific standardised incidence ratios (SIRs) were calculated from the Nordic Occupational Cancer (NOCCA) database.Main Outcome Measures: Incidence rates and standardised incidence ratios.Results: The age-adjusted (World Standard) incidence rates remained quite constant: about 0.6-0.8 per 100 000 for most of the study period. The age-specific incidence was highest at 50-64 years of age. There were no occupations with significantly increased risk of GCT. Major changes in the use of oral contraceptives, postmenopausal hormonal therapy, fertility rate and lifestyle in general during the study period and among different occupational categories do not appear to have a marked effect on the incidence of GCT.Conclusion: Our findings support the concept of GCT as a primarily sporadic, not exposure-related, cancer.Tweetable Abstract: The Nordic incidence rates of GCTs show stability over time and among different occupational categories. [ABSTRACT FROM AUTHOR]

Objectives: To estimate total and cause-specific mortality after international peacekeeping deployments among the Finnish military peacekeeping personnel in comparison to the general population of similar age and sex. Design: A register-based study of a cohort of military peacekeeping personnel in 1990–2010 followed for mortality until the end of 2013. Causes of death were obtained from the national Causes of Death Register. The standardised mortality ratio (SMR) for total and cause-specific mortality was calculated as the ratio of observed and expected number of deaths. Setting: Finland (peacekeeping operations in different countries in Africa, Asia and in an area of former Yugoslavia in Europe). Participants: 14 584 men and 418 women who had participated in international military peacekeeping operations ending between 1990 and 2010. Interventions: Participation in military peacekeeping operations. Main outcome: Total and cause-specific mortality. Results: 209 men and 3 women died after their peacekeeping service. The SMR for all-cause mortality was 0.55 (95% CI 0.48 to 0.62). For the male peacekeeping personnel, the SMR for all diseases was 0.44 (95% CI 0.35 to 0.53) and for accidental and violent deaths 0.69 (95% CI 0.57 to 0.82). The SMR for suicides was 0.71 (95% CI 0.53 to 0.92). Conclusions: Even though military peacekeeping personnel are working in unique and often stressful conditions, their mortality after their service is lower compared with the general population. Military peacekeeping personnel appear to be a selected population group with low general mortality and no excess risk of any cause of death after peacekeeping service. [ABSTRACT FROM AUTHOR]

Background:For an effective colorectal cancer (CRC) screening program, high participation rate is essential. However, non-participation in CRC screening program has increased in Finland. Material and methods:The study was based on a population-based nationwide cohort of persons invited for CRC screening in 2004–2011. Information on the first round of the CRC screening participation and related background factors was obtained from the Finnish Cancer Registry, and information about health behavior factors from the Health Behavior Survey (HBS) in 1978–1999. Non-participation in CRC screening was analyzed with Poisson regression as incidence rate ratios (IRR) with 95% confidence intervals (95% CI). Results:Of all persons invited for CRC screening (79 871 men and 80 891 women) 35% of men and 21% of women refused. Of those invited for screening, 2456 men (3.1%) and 2507 women (3.1%) were also invited to the HBS. Persons, who declined HBS, were also more likely to refuse CRC screening (men IRR 1.40, 95% CI 1.26–1.56, women 1.75, 1.52–2.02) compared to HBS participants. Never married persons had about a 75% higher risk for refusing than married ones. The youngest age group (60 years) was more likely to refuse screening than the older age groups (62 or >64 years). Smoking was associated with non-participation in screening (current smokers, men: IRR 1.32, 95% CI 1.05–1.67, women: 2.10, 1.61–2.73). Conclusions:Participation in CRC screening was affected by gender, age, and marital status. Persons, who refused the HBS, were also more likely to refuse CRC screening. Smoking was a risk factor for non-participation in CRC screening. [ABSTRACT FROM PUBLISHER]

ObjectiveFinasteride 5 mg is a drug used to treat prostate hyperplasia. Little is known about its pattern of usage. This cross-national analysis of individual-level data from Denmark, Finland, Norway and Sweden was undertaken to appraise its usage and describe cross-national differences.Materials and methodsIndividual-level data from nationwide prescription registers in Denmark (1995–2009), Finland (1997–2010), Norway (2004–2009) and Sweden (July 2005–2011) were used to examine cross-national finasteride utilization patterns in the adult male population (≥15 years). The study presents period prevalences, incidence rates, waiting time distributions and Lorenz curves.ResultsDuring the study period, 295,620 men had at least one prescription redemption of finasteride 5 mg, and there were approximately 3 million dispensing events of finasteride prescriptions in the four Nordic countries. Different patterns of finasteride use were observed among the four Nordic countries. The period prevalence was markedly higher in Finland and Sweden than in Denmark and Norway. In 2009, period prevalences were 18.2/1000 males in Finland and 12.0/1000 males in Sweden compared to 6.7/1000 males in Norway and 4.9/1000 males in Denmark. Incidence rates of finasteride use for Finland, Norway and Sweden were about three times that for Denmark in 2008–2009. Long-term use of finasteride was found in all four Nordic countries with a high ratio between prevalent and incident users.ConclusionDespite resemblances regarding political systems and healthcare services in the Nordic countries, differences in finasteride utilization were found across Denmark, Finland, Norway and Sweden. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Background Melanoma is a significant health problem in Caucasian populations. The most recently available data from cancer registries often have a delay of several months up to a few years and they are generally not easily accessible. Objectives To assess recent age- and sex-specific trends in melanoma incidence and make predictions for 2010 and 2015. Methods A retrospective registry-based analysis was performed with data from 29 European cancer registries. Most of them had data available from 1990 up to 2006/7. World-standardized incidence rates ( WSR) and the estimated annual percentage change ( EAPC) were computed. Predictions were based on linear projection models. Results Overall the incidence of melanoma is rapidly rising and will continue to do so. The incidence among women in Europe was generally higher than in men. The highest incidence rates were seen for Northern and north-western countries like the UK, Ireland and the Netherlands. The lowest incidence rates were observed in Portugal and Spain. The incidence overall remained stable in Norway, where, amongst young (25-49 years) Norwegian males rates significantly decreased ( EAPC −2.8, 95% CI −3.6; −2.0). Despite a low melanoma incidence among persons above the age of 70, this age group experienced the greatest increase in risk during the study period. Conclusions Incidence rates of melanoma are expected to continue rising. These trends are worrying in terms of disease burden, particularly in eastern European countries. [ABSTRACT FROM AUTHOR]

Purpose: Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer. Methods: A case-control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986-2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations. Results: Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49-1.77 for top vs. bottom tertile, P = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49-0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06-2.54) was observed in younger women, P = 0.002. Conclusions: In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement. [ABSTRACT FROM AUTHOR]

Objective While previous data link the use of postmenopausal hormone therapy to an increased risk for ovarian cancer, little is known about the impact of various progestins, modes or routes of administration of hormone therapy for this risk. In this nationwide study, we compared relations between different estradiol--progestin (EPT) formulations and epithelial ovarian cancer risk. Methods All Finnish women over 50 years using EPT for at least 6 months (224015 women with 602 ovarian cancers) during 1994--2006 were identified from the reimbursement register. The incidence of ovarian cancer in EPT users was compared to that in the age-matched background population by means of observed to expected ratio (standardized incidence ratio, SIR). Results Ovarian cancer risk was not elevated for EPT use of <5 years but it was elevated for EPT use of ≥5 years (SIR 1.21, 95% confidence interval (CI) 1.06--1.37). Medroxyprogesterone acetate and norethisterone acetate as components of EPT were associated with similar risks for use for ≥5 years (SIR 1.26, 95% CI 0.94--1.64 and SIR 1.42, 95% CI 1.11--1.77, respectively). The risk did not differ between sequential or continuous EPT regimens or between oral or transdermal EPT formulations. The risk elevation for EPT use for ≥5 years was seen only for serous (SIR 1.56; 95% CI 1.33--1.80) and mixed cancers (SIR 1.54; 95% CI 1.22--1.91), whereas the risk for mucinous cancer was decreased (SIR 0.47; 95% CI 0.22--0.86). Conclusion The elevated risk of non-mucinous ovarian cancer in users of EPT ≥ 5 years does not depend on progestin type, mode or route of administration of EPT. [ABSTRACT FROM AUTHOR]

Background Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac disease and most patients adhere to a life-long gluten free diet (GFD). Increased mortality rates have been reported in coeliac disease but knowledge in DH is scanty. Objectives To survey the mortality rate and causes of death in a large cohort of patients with DH. Material and methods Patients with DH ( n = 476 consecutive patients) diagnosed from 1970 onwards at the Tampere University Hospital were analysed for causes of death during 1971-2010. A questionnaire survey on key aspects of health behaviour was performed in patients with DH and comparisons were made with the Finnish population. Results The total number of deaths during 9079 person years followed up was 77 whereas 110 were expected. The standardized mortality rate (SMR) for all causes of death was significantly reduced, being 0·70 (95% CI 0·55-0·87), and similar in both sexes. The SMR was equal in the patients with DH with (0·73) and without (0·77) small bowel villous atrophy. The SMR was significantly reduced (0·38) for deaths due to cerebrovascular diseases. The SMR due to lymphoproliferative malignancies was significantly increased (6·86) in the first 5 years of follow-up but not thereafter. The questionnaire survey documented that 97·7% of the patients with DH adhered to a GFD. The patients reported significantly less hypercholesterolaemia and there were fewer current and past smokers compared with the age- and sex-matched control population. Conclusions The present long-term follow-up study of DH documented significantly reduced all-cause and cerebrovascular disease mortality. Strict adherence to a GFD, less smoking and hypercholesterolaemia may play a role in the observed health benefit. [ABSTRACT FROM AUTHOR]

The aetiology of primary Fallopian tube carcinoma (PFTC) is poorly understood. Occupational exposures may contribute to PFTC risk. We studied incidence of PFTC in occupational categories in the Nordic female population aged 30-64 years during the 1960, 1970, 1980/1981 and/or 1990 censuses in Denmark, Finland, Iceland, Norway and Sweden. Standardized incidence ratios (SIRs) for the years following inclusion in the study up to 2005 were calculated for 53 occupations; the expected numbers of cases were based on PFTC incidence in the national populations. Altogether 2,206 PFTC cases were detected during follow up via data linkages with the Nordic cancer registries. Significantly increased risks of PFTC were observed for smelting workers (SIR 3.99, 95% confidence interval 1.46-8.68, Obs = 6), artistic workers (2.64, 1.44-4.43, Obs = 14), hairdressers (2.18, 1.41-3.22, Obs = 25), packers (1.62, 1.11-2.29, Obs = 32), nurses (1.49, 1.14-1.92, Obs = 60), shop workers (1.25, 1.07-1.46, Obs = 159) and clerical workers (1.20, 1.07-1.35, Obs = 271) and these sustained over times and different Nordic countries. There was a nonsignificant increased risk for PFTC among welders, printers, painters and chemical process workers. The risk was significantly and consistently low for women working in farming (0.68, 0.47-0.95, Obs = 34) and among economically inactive women (0.88, 0.82-0.94, Obs = 833). The possible role of occupational exposures to the PFTC risks found in this study must be further evaluated in studies with a possibility to adjust for possible confounding factors, such as reproductive and life-style factors, which was not possible in our study. [ABSTRACT FROM AUTHOR]

Objective: A short interval between the first and second birth was associated with an increased risk of advanced ductal breast cancer among women with 5+ childbirths in our previous study. We now evaluated the significance of this risk factor and its relation to the age at first birth among mothers with 2-4 children. Methods: The cohort of 190,949 Finnish women with 2-4 children comprised 3,834 women with ductal breast cancer diagnosed before 2009. Conditional logistic regression for case-control design nested within the cohort was used to estimate proportional hazard ratios (HR) associated with the birth interval. Controls were matched for age and number of children. Age at the first birth and the interval from the last birth to cancer were co-variables. Results: Among women with the first birth <30 years, the HR of advanced ductal breast cancer at 50+ years for a short (<1.5 years) versus long (>3 years) interval between the first and second birth was 0.48 (95% Confidence Interval 0.33-0.70). Among women with the first birth at 30+ years, the HR of this cancer type diagnosed before the age of 50 years for a short versus long interval between the first and second birth was 5.83 (95% CI 2.30-14.8). Conclusion: The interval between first and second birth strongly influences the risk of ductal breast cancer. Because second pregnancy soon after the first one decreased the risk of ductal breast cancer in young primiparas but increased the risk in older primiparas, it is likely that in such circumstances second pregnancy continues the actions initiated by the first pregnancy/breast-feeding. [ABSTRACT FROM AUTHOR]

Impaired semen quality and testicular cancer may be linked through a testicular dysgenesis syndrome of foetal origin. The incidence of testis cancer has been shown to increase among Finnish men, whereas there is no recent publication describing temporal trends in semen quality. Therefore, we carried out a prospective semen quality study and a registry study of testis cancer incidence among Finnish men to explore recent trends. A total of 858 men were investigated in the semen quality study during 1998-2006. Median sperm concentrations were 67 (95% CI 57-80) million/mL, 60 (51-71) and 48 (39-60) for birth cohorts 1979-81, 1982-83 and 1987; total sperm counts 227 (189272) million, 202 (170-240) and 165 (132-207); total number of morphologically normal spermatozoa 18 (14-23) million, 15 (12-19) and 11 (8-15). Men aged 10-59 years at the time of diagnosis with testicular cancer during 19542008 were included in the registry study, which confirmed the increasing incidence of testicular cancer in recent cohorts. These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and, as such, preventable. Our findings necessitate not only further surveillance of male reproductive health but also research to detect and remove the underlying factors. [ABSTRACT FROM AUTHOR]

Background: Relative survival after cancer in Finland is at the highest level observed in Europe and has, in general, been on a steady increase. The aim of this study is to assess whether the high survival is equally shared by different population subgroups and to estimate the possible gains that might be achieved if equity prevailed.Materials and Method: The educational level and occupation before the cancer diagnosis of patients diagnosed in Finland in 1971-2005 was derived from an antecedent population census. The cancers were divided into 27 site categories. Cancer (cause)-specific 5-year survival proportions were calculated for three patient categories based on the educational level and for an occupational group of potentially health-conscious patients (physicians, nurses, teachers etc.). Proportions of avoidable deaths were derived by assuming that the patients from the two lower education categories would have the same mortality owing to cancer, as those from the highest educational category. Estimates were also made by additionally assuming that even the mortalities owing to other causes of death were all equal to those in the highest category.Results: For almost all the sites considered, survival was consistently highest for patients with the highest education and lowest for those with only basic education. The potentially health-conscious patients had an even higher survival. The differences were, in part, attributable to less favourable distributions of tumour stages in the lower education categories. In 1996-2005, 4-7% of the deaths in Finnish cancer patients could have potentially been avoided during the first 5-year period after diagnosis, if all the patients had the same cancer mortality as the patients with the highest educational background. The proportion would have also been much higher, 8-11%, if, in addition, the mortality from other causes had been the same as that in the highest educational category.Interpretation: Even in a potentially equitable society with high health care standards, marked inequalities persist in cancer survival. Earlier cancer diagnosis and the ability to cope within the health care system may be a partly relevant explanation, but personal habits and lifestyles also have a role, particularly for the cancer patients' mortality from other causes of death than cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives:The possible association between coffee consumption and risk of colorectal cancer has been extensively studied in the many populations. The aim of this study is to examine this relationship among Finns, who are the heaviest coffee consumers in the world.Subjects/Methods:A total of 60 041 Finnish men and women who were 26–74 years of age and without history of any cancer at baseline were included in the present analyses. Their coffee consumption and other study characteristics were determined at baseline, and they were prospectively followed up for onset of colon and rectal cancer, emigration, death or until 30 June 2006.Results:During a mean follow-up period of 18 years, 538 cases of colorectal cancer (304 cases of colon cancer and 234 cases of rectal cancer) were diagnosed. The multivariate-adjusted hazard ratio of colorectal cancer incidence for 10 cups of coffee per day compared with non-drinkers was 0.98 (95% CI, 0.47–2.03) for men (P for trend=0.86), 1.24 (95% CI, 0.49–3.14) for women (p for trend=0.83) and 1.03 (95% CI, 0.58–1.83) for men and women combined (P for trend=0.61).Conclusions:In this study, we found no association between coffee consumption and the risk of colorectal, colon and rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Familial nervous system cancers are rare and limited data on familial aspects are available particularly on site-specific tumours.Methods: Data from five Nordic countries were used to analyse familial risks of nervous system tumours. Standardised incidence ratios (SIRs) were calculated for offspring of affected relatives compared with offspring of non-affected relatives.Results: The total number of patients with nervous system tumour was 63 307, of whom 32 347 belonged to the offspring generation. Of 851 familial patients (2.6%) in the offspring generation, 42 (4.7%) belonged to the families of a parent and at least two siblings affected. The SIR of brain tumours was 1.7 in offspring of affected parents; it was 2.0 in siblings and 9.4 in families with a parent and sibling affected. For spinal tumours, the SIRs were much higher for offspring of early onset tumours, 14.0 for offspring of affected parents and 22.7 for siblings. The SIRs for peripheral nerve tumours were 16.3 in offspring of affected parents, 27.7 in siblings and 943.9 in multiplex families.Conclusion: The results of this population-based study on medically diagnosed tumours show site-, proband- and age-specific risks for familial tumours, with implications for clinical genetic counselling and identification of the underlying genes. [ABSTRACT FROM AUTHOR]

The NORDCAN database and program () include detailed information and results on cancer incidence, mortality and prevalence in each of the Nordic countries over five decades and has lately been supplemented with predictions of cancer incidence and mortality; future extensions include the incorporation of cancer survival estimates. Material and methods. The data originates from the national cancer registries and causes of death registries in Denmark, Finland, Iceland, Norway, Sweden, and Faroe Islands and is regularly updated. Presently 41 cancer entities are included in the common dataset, and conversions of the original national data according to international rules ensure comparability. Results. With 25 million inhabitants in the Nordic countries, 130 000 incident cancers are reported yearly, alongside nearly 60 000 cancer deaths, with almost a million persons living with a cancer diagnosis. This web-based application is available in English and in each of the five Nordic national languages. It includes comprehensive and easy-to-use descriptive epidemiology tools that provide tabulations and graphs, with further user-specified options available. Discussion. The NORDCAN database aims to provide comparable and timely data to serve the varying needs of policy makers, cancer societies, the public, and journalists, as well as the clinical and research community. [ABSTRACT FROM AUTHOR]

Background: Patterns of second primary cancers (SPCs) following first primary lung cancers (FPLCs) may provide aetiological insights into FPLC.Methods: Cases of FPLCs in 13 cancer registries in Europe, Australia, Canada, and Singapore were followed up from the date of FPLC diagnosis to the date of SPC diagnosis, date of death, or end of follow-up. Standardised incidence ratios (SIRs) were calculated to estimate the magnitude of SPC development following squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC), and adenocarcinoma (ADC).Results: Among SCC patients, male SIR=1.58 (95% confidence interval (CI)=1.50-1.66) and female SIR=2.31 (1.94-2.72) for smoking-related SPC. Among SCLC patients, the respective ratios were 1.39 (1.20-1.60) and 2.28 (1.73-2.95), and among ADC patients, they were 1.73 (1.57-1.90) and 2.24 (1.91-2.61). We also observed associations between first primary lung ADC and second primary breast cancer in women (SIR=1.25, 95% CI=1.05-1.48) and prostate cancer (1.56, 1.39-1.79) in men.Conclusion: The FPLC patients carried excess risks of smoking-related SPCs. An association between first primary lung ADC and second primary breast and ovarian cancer in women at younger age and prostate cancers in men may reflect an aetiological role of hormones in lung ADC. [ABSTRACT FROM AUTHOR]

Background and purpose Wear debris from conventional total hip arthroplasty (THA) induces chromosomal aberrations and DNA damage, which may promote cancerogenesis. A long latent period is required for solid tumors. We therefore re-analyzed a large THA cohort for cancer. Patients and methods We updated a cohort of 24,636 patients with primary osteoarthritis and metal-on-polyethylene THA who had been entered in the Finnish Arthroplasty Register between 1980 and 1995, and linked it to the Finnish Cancer Registry for cancer risk assessment up to 2005. The mean follow-up time was 13 years. The numbers of cancer cases observed were compared with expected rates based on incidence in the general population. Results The standardized incidence ratio (SIR) for the whole follow-up period was 0.95 (95% confidence interval (CI): 0.92-0.97). After 10 years of follow-up, the SIR was equal to that in the normal population (SIR = 0.98, 95% CI: 0.94-1.03). Incidence of lung cancer was low throughout the follow-up time and that of prostate cancer was slightly elevated. The incidence rates for all other forms of cancer did not deviate significantly from those in the normal population. Interpretation We found no increased cancer risk in patients with conventional THA after an average of 13 years and up to 25 years of follow-up. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression and Merkel-cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin.Methods: We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR.Results: We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2-64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2-46.0, P<0.01). Merkel-cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis.Conclusions: We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC. [ABSTRACT FROM AUTHOR]

Background: The interval between successive births (birth interval) may affect breast cancer risk, whereas interval from last birth to cancer onset may modify its behaviour.Methods: The study cohort consisted of 29 488 Finnish grand multiparous (GM) women, including 628 women with breast cancer. Conditional logistic regression for case-control design nested within the cohort was used to estimate proportional hazards (referred as relative risks, RR). Age at first birth and parity were co-variables.Results: Short interval (<1 year) between first and second birth increased the risk of advanced ductal breast cancer at ages < 50 years (RR=5.29; 95% CI 2.00-14.0) as compared to interval 3+ years. The risk of advanced ductal cancer was also large (RR = 4.00; 95% CI 1.19-13.4) shortly (<3 years) after last birth as compared with the period 15+ years.Conclusions: Short birth interval-associated excess breast cancer risk may be related to stimulatory effects of female steroid hormones produced during two closely connected pregnancies, or defective breast maturation owing to failures in breastfeeding. [ABSTRACT FROM AUTHOR]

We present up to 45 years of cancer incidence data by occupational category for the Nordic populations. The study covers the 15 million people aged 30-64 years in the 1960, 1970, 1980/1981 and/or 1990 censuses in Denmark, Finland, Iceland, Norway and Sweden, and the 2.8 million incident cancer cases diagnosed in these people in a follow-up until about 2005. The study was undertaken as a cohort study with linkage of individual records based on the personal identity codes used in all the Nordic countries. In the censuses, information on occupation for each person was provided through free text in self-administered questionnaires. The data were centrally coded and computerised in the statistical offices. For the present study, the original occupational codes were reclassified into 53 occupational categories and one group of economically inactive persons. All Nordic countries have a nation-wide registration of incident cancer cases during the entire study period. For the present study the incident cancer cases were classified into 49 primary diagnostic categories. Some categories have been further divided according to sub-site or morphological type. The observed number of cancer cases in each group of persons defined by country, sex, age, period and occupation was compared with the expected number calculated from the stratum specific person years and the incidence rates for the national population. The result was presented as a standardised incidence ratio, SIR, defined as the observed number of cases divided by the expected number. For all cancers combined (excluding non-melanoma skin cancer), the study showed a wide variation among men from an SIR of 0.79 (95% confidence interval 0.66\'010.95) in domestic assistants to 1.48 (1.43-1.54) in waiters. The occupations with the highest SIRs also included workers producing beverage and tobacco, seamen and chimney sweeps. Among women, the SIRs varied from 0.58 (0.37-0.87) in seafarers to 1.27 (1.19-1.35) in tobacco workers. Low SIRs were found for farmers, gardeners and teachers. Our study was able to repeat most of the confirmed associations between occupations and cancers. It is known that almost all mesotheliomas are associated with asbestos exposure. Accordingly, plumbers, seamen and mechanics were the occupations with the highest risk in the present study. Mesothelioma was the cancer type showing the largest relative differences between the occupations. Outdoor workers such as fishermen, gardeners and farmers had the highest risk of lip cancer, while the lowest risk was found among indoor workers such as physicians and artistic workers. Studies of nasal cancer have shown increased risks associated with exposure to wood dust, both for those in furniture making and for those exposed exclusively to soft wood like the majority of Nordic woodworkers.We observed an SIR of 1.84 (1.66-2.04) in male and 1.88 (0.90-3.46) in female woodworkers. For nasal adenocarcinoma, the SIR in males was as high as 5.50 (4.60-6.56). Male waiters and tobacco workers had the highest risk of lung cancer, probably attributable to active and passive smoking. Miners and quarry workers also had a high risk, which might be related to their exposure to silica dust and radon daughters. Among women, tobacco workers and engine operators had a more than fourfold risk as compared with the lung cancer risk among farmers, gardeners and teachers. The occupational risk patterns were quite similar in all main histological subtypes of lung cancer. Bladder cancer is considered as one of the cancer types most likely to be related to occupational carcinogens. Waiters had the highest risk of bladder cancer in men and tobacco workers in women, and the low-risk categories were the same ones as for lung cancer. All this can be accounted for by smoking. The second-highest SIRs were among chimney sweeps and hairdressers. Chimney sweeps are exposed to carcinogens such as polycyclic aromatic hydrocarbons from the chimney soot, and hairdressers' work environment is also rich in chemical agents. Exposure to the known hepatocarcinogens, the Hepatitis B virus and aflatoxin, is rare in the Nordic countries, and a large proportion of primary liver cancers can therefore be attributed to alcohol consumption. The highest risks of liver cancer were seen in occupational categories with easy access to alcohol at the work place or with cultural traditions of high alcohol consumption, such as waiters, cooks, beverage workers, journalists and seamen. The risk of colon cancer has been related to sedentary work. The findings in the present study did not strongly indicate any protective role of physical activity. Colon cancer was one of the cancer types showing the smallest relative variation in incidence between occupational categories. The occupational variation in the risk of female breast cancer (the most common cancer type in the present series, 373 361 cases) was larger, and there was a tendency of physically demanding occupations to show SIRs below unity. Women in occupations which require a high level of education have, on average, a higher age at first child-birth and elevated breast cancer incidence. Women in occupational categories with the highest average number of children had markedly lower incidence. In male breast cancer (2 336 cases), which is not affected by the dominating reproductive factors, there was a suggestion of an increase in risk in occupations characterised by shift work. Night-shift work was recently classified as probably carcinogenic, with human evidence based on breast cancer research. The most common cancer among men in the present cohort was prostate cancer (339 973 cases). Despite the huge number of cases, we were unable to demonstrate any occupation-related risks. The observed small occupational variation could be easily explained by varying PSA test frequency. The Nordic countries are known for equity and free and equal access to health care for all citizens. The present study shows that the risk of cancer, even under these circumstances, is highly dependent on the person's position in the society. Direct occupational hazards seem to explain only a small percentage of the observed variation -- but still a large number of cases -- while indirect factors such as life style changes related to longer education and decreasing physical activity become more important. This publication is the first one from the extensive Nordic Occupational Cancer (NOCCA) project. Subsequent studies will focus on associations between specific work-related factors and cancer diseases with the aim to identify exposureresponse patterns. In addition to the cancer data demonstrated in the present publication, the NOCCA project produced Nordic Job Exposure Matrix (described in separate articles in this issue of Acta Oncologica) that transforms information about occupational title histories to quantitative estimates of specific exposures. The third essential component is methodological development related to analysis and interpretation of results based on averaged information of exposures and co-factors in the occupational categories. [ABSTRACT FROM AUTHOR]

Introduction. The Nordic Occupational Cancer study (NOCCA) is a cohort study based on employed populations in one or more censuses in Denmark, Finland, Iceland, Norway and Sweden. The large size of the cohort allows us to study rare cancers and to identify even small risks by occupation and by specific occupational exposures. This paper describes principles and experiences of the construction of job-exposure matrices (JEMs), an instrument to transform the history of occupational titles into quantitative estimates of exposure to potential carcinogenic substances. Material and methods. For each Nordic country, a national JEM was constructed by a team of experts on the basis of the Finnish matrix (FINJEM) that has been used in similar national studies since the mid-1990s. Results. The structure of the Nordic JEMs is three-dimensional (over 300 occupations, over 20 agents, 4 periods covering 1945-1994). Exposure is characterised by estimates of the prevalence and level of exposure. Important differences between the Nordic countries were observed for several exposures. Discussion. The selection of priority agent-occupation combinations and the adoption of general principles in the beginning of the work were necessary because of the high number of estimates to be evaluated (over 50 000/country). The selective modification of an existing JEM for use in other countries was a feasible, albeit challenging task, because exposure data and information about the use of chemicals in the past was scanty. As compared to the use of FINJEM for all Nordic countries, the modification process will probably increase the validity of dose-response and risk estimates of occupational cancer which is to be expected soon as the main outcome of the NOCCA project. [ABSTRACT FROM AUTHOR]

Background Fragile X syndrome is a common inheritable cause of intellectual disability (ID) and is characterised by a large number of CGG repeats at the gene FMR1 located on the X-chromosome. It has been reported that this genetic mechanism may protect against malignant transformations. Methods We extracted from the Finnish registry on persons with ID a cohort of 302 persons with a fragile X diagnosis during 1982–1986. Follow-up for cancer incidence was performed in the Finnish Cancer Registry until the end of the year 2005. Results There were 11 reported cancers during the mean follow-up of 21.4 years per person. The expected number of cancers based on the average Finnish population was 13.8 and no statistically significant protective effect was detected [standardised incidence ratios (SIR) 0.80, confidence interval (CI) 95% 0.40–1.4]. An increased risk for lip cancer was found (SIR 23, CI 95% 2.8–85). Conclusions Confirmation of hypotheses about the mechanisms linking FXS and cancer needs further research. [ABSTRACT FROM AUTHOR]

Background: Some environmental moulds and bacteria produce carcinogenic toxins. Aim: To study associations between work-related exposure to moulds and bacteria and cancers in Finland. Methods: A cohort of all economically active Finns in the population census in 1970 were followed-up for 30 million person-years. Subsequent cancer cases were identified through record linkage with the Finnish Cancer Registry. Observed and expected numbers of cancer cases were calculated by occupation, sex, birth cohort and period of observation. Exposures to moulds of agricultural and industrial origin and to bacteria of non-human origin were estimated with the Finnish Job-Exposure Matrix. Results: Men with the highest mould and bacterial exposure had a reduced relative risk for lung cancer (RH 0.7, 95% Cl 0.6 to 0.9 for moulds and RR 0.9, 95% CI 0.8 to 1.0 for bacteria). Women in the highest mould and bacterial exposure category had RRs of 3.1 (95% Cl 1.0 to 9.2) and 2.6 (95% Cl 1.5 to 4.7) for cervical cancer, respectively. The respective RRs for lip cancer were 2.4 (95% CI 1.2 to 5.1) and 1.6 (95% CI 1.2 to 2.2). Conclusions: Exposures at the investigated concentrations to either moulds or bacteria are unlikely to be major risk factors of cancer, although suggestions of risk increases were observed for some cancer types. It has been suggested previously that the decreased risk for lung cancer is due to the protective effect of endotoxins. [ABSTRACT FROM AUTHOR]

Background and objective: Methylating agents are effective chemotherapy agents for Hodgkin lymphoma, but are associated with the development of second primary cancers. Cytotoxicity of methylating agents is mediated primarily by the DNA mismatch repair (MMR) system. Loss of MLH1, a major component of DNA MMR, results in tolerance to the cytotoxic effects of methylating agents and persistence of mutagenised cells at high risk of malignant transformation. We hypothesised that a common substitution in the basal promoter of MLH1 (position -93, rs 1800734) modifies the risk of cancer after methylating chemotherapy. Methods: 133 patients who developed cancer following chemotherapy and/or radiotherapy In = 133), 420 patients diagnosed with de novo myeloid leukaemia, 242 patients diagnosed with primary Hodgkin lymphoma, and 1177 healthy controls were genotyped for the MLH1 -93 polymorphism by allelic discrimination polymerase chain reaction (PCR) and restriction fragment length polymorphism assay. Odds ratios and 95% confidence intervals for cancer risk by MLH1 -93 polymorphism status, and stratified by previous exposure to methylating chemotherapy, were calculated using unconditional logistic regression. Results: Carrier frequency of the MLH1 -93 variant was higher in patients who developed therapy related acute myeloid leukaemia (t-AML) (75.0%, n = 12) or breast cancer (53.3%. n = 15) after methylating chemotherapy for Hodgkin lymphoma compared to patients without previous methylating exposure (t-AML, 30.4%, n = 69; breast cancer patients, 27.2%, n = 221. The MLH1 -93 variant allele was also over-represented in t-AML cases when compared to de novo AML cases (36.9%, n = 420) and healthy controls (36.3%, n = 952), and was associated with a significantly increased risk of developing t-AML (odds ratio 5.31, 95% confidence interval 1.40 to 20.15), but only in patients previously treated with a methylating agent. Conclusions: These data support the hypothesis that the common polymorphism at position -93 in the core promoter of MLH1 defines a risk allele for the development of cancer after methylating chemotherapy for Hodgkin lymphoma. However, replication of this finding in larger studies is suggested. [ABSTRACT FROM AUTHOR]

Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed. [ABSTRACT FROM AUTHOR]

After identifying an association between maternal Epstein-Barr virus (EBV) reactivation and acute lymphoblastic leukemia (ALL), the authors analyzed a nested case-control study within Finnish and Icelandic maternity cohorts with 7 million years of follow-up to confirm EBV's role in ALL. Offspring of 550,000 mothers were followed up to age 15 years during 1975-1997 by national cancer registries to identify leukemia cases. Mothers of cases and three quarters of matched mothers of controls were identified by national population registers. First-trimester sera from mothers of 304 ALL cases and 39 non-ALL cases and from 943 mothers of controls were analyzed for antibodies to viral capsid antigen, early antigen, and EBV transactivator protein ZEBRA. Relative risk, estimated as odds ratio (95% confidence interval), was adjusted for birth order and sibship size. Combining early antigen and/or ZEBRA immunoglobulin G antibodies with the presence of viral capsid antigen immunoglobulin M antibodies did not increase the estimate for ALL risk for viral capsid antigen immunoglobulin M alone (odds ratio = 1.9, 95% confidence interval: 1.2, 3.0). Both ZEBRA immunoglobulin G antibodies and viral capsid antigen immunoglobulin M antibodies were associated with an increased risk of non-ALL in the offspring (odds ratio = 4.5, 95% confidence interval: 1.3, 16; odds ratio = 5.6, 95% confidence interval: 1.1, 29, respectively), suggesting EBV reactivation in the mothers of non-ALL cases. EBV reactivation may be associated with a proportion of childhood leukemia. [ABSTRACT FROM AUTHOR]

Background: There is inconclusive evidence concerning cancer risks of organic dusts. Aim: The carcinogenic exposures are mainly inhalatory and the authors therefore studied associations between occupational exposure to eight different organic dusts and respiratory cancers in Finland. Methods: The authors followed up a cohort of all economically active Finns born between 1906 and 1945 for 30 million person-years during 1971-95. Incident cases of nasal, laryngeal, and lung cancer and mesotheliomas were identified through a record linkage with the Finnish Cancer Registry. Occupations from the population census in 1970 were converted to exposures to eight organic dusts with a job-exposure matrix (FINJEM). Cumulative exposure (CE) was calculated as a product of prevalence, level, and estimated duration of exposure. Standardised incidence ratios (SIR) and 95% confidence intervals (CI) adjusted for age, period, and social class were calculated for each organic dust using the economically active population as the reference. Results: A total of 20 426 incident cases of respiratory cancer were observed. Slightly increased risk was observed among men exposed to wood dust for nasal cancer (SIR 1.42, 95% CI 0.79 to 2.44). For laryngeal cancer, men exposed to plant dust (mainly grain millers) had a raised SIR in the high exposure class (SIR 3.55, 95% CI 1.30 to 7.72). Men exposed to wood dust had a raised SIR for lung cancer, but only in the low exposure class (SIR 1.11, 95% CI 1.04 to 1.18). Women exposed to wood dust showed an increased SIR for mesotheliomas in the low exposure class (SIR 4.57, 95% CI 1.25 to 11.7) and some excess in the medium exposure category. Conclusions: Exposure to organic dusts is unlikely to be a major risk factor of respiratory cancer. Even exposure to wood dust which is a major exposure in Finland seems to have minor effect for nasal cancer. The authors found suggestive evidence that exposure to grain dust may increase the risk of laryngeal cancer, and some support to the hypothesis that exposure to textile dust, and to plant and animal dust (agricultural dusts) may decrease the risk of lung cancer. [ABSTRACT FROM AUTHOR]

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumour predisposition syndrome caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. The condition is characterised by predisposition to benign leiomyomas of the skin and the uterus, renal cell carcinoma (RCC), and uterine leiomyosarcoma (ULMS). To comprehensively examine the cancer risk and tumour spectrum in Finnish FH mutation positive families, genealogical and cancer data were obtained from 868 individuals. The cohort analysis of the standardised incidence ratios (SIR) was analysed from 256 individuals. FH mutation status was analysed from all available individuals (n=98). To study tumour spectrum in FH mutation carriers, loss of the wild type allele was analysed from all available tumours (n=22). The SIR was 6.5 for RCC and 71 for ULMS. The overall cancer risk was statistically significantly increased in the age group of 15-29 years, consistent with features of cancer predisposition families in general. FH germline mutation was found in 55% of studied individuals. Most RCC and ULMS tumours displayed biallelic inactivation of FH, as did breast and bladder cancers. In addition, several benign tumours including atypical uterine Ieiomyomas, kidney cysts, and adrenal gland adenomas were observed. The present study confirms with calculated risk ratios the association of early onset RCC and ULMS with FH germline mutations in Finns. Some evidence for association of breast and bladder carcinoma with HLRCC was obtained. The data enlighten the organ specific malignant potential of HLRCC. [ABSTRACT FROM AUTHOR]

We evaluated a study setting for assessment of the long-term vaccine efficacy (VE) of human papillomavirus (HPV) virus-like-particle (VLP) vaccine against cervical carcinoma. A total of 22,412 16- to 17-year old adolescent women from seven cities in Finland were invited by letter to participate in a phase III study of a quadrivalent HPV (types 6, 11, 16, 18) VLP vaccine, between September 2002 and March 2003. A total of 30,947 18-year old women were invited to participate as unvaccinated controls. These women were asked about their willingness to participate in an HPV vaccination trial and to fill a health questionnaire. These three population-based cohorts of adolescent women, including women vaccinated with HPV vaccine or placebo vaccine and unvaccinated control women, are systematically followed over time. The study cohort database will be linked with the Finnish Cancer Registry using cervical carcinoma in situ (CIS) and invasive cervical carcinoma (ICC) as endpoints. Assuming that the cumulative incidence of CIS and ICC over 15 years is 0.45%, and that there is no loss to follow-up, and power of 80%, the determination of 70% total VE will require 3357 HPV vaccine recipients, 3357 placebo vaccine recipients, and 6714 unvaccinated controls. At the baseline, 2632 (12%) of the invited adolescents volunteered to the phase III vaccination trial, and 6790 (22%) responded to the questionnaire study. During a recruitment period of 10 months, 874 HPV vaccine recipients, 875 placebo recipients and 1919 unvaccinated controls were enrolled. Population-based enrolment of large cohorts of vaccinated and unvaccinated adolescents for passive registry-based follow-up with cervical carcinoma as the end-point is feasible and currently going on in Finland. [ABSTRACT FROM AUTHOR]

BACKGROUND: Belief that depression and other psychological factors predict breast cancer is common, but there have been few prospective epidemiological studies on this relationship. METHOD: The relationship between depression, personality traits, illness attitudes, life events and health history, and breast cancer risk was studied in a prospective, 6-9 year follow-up of a cohort study of 10892 Finnish women of 48-50 years of age at the baseline. Cancer cases were obtained from the Cancer Registry of Finland. Multivariate logistic regression analysis was performed controlling for socioeconomic factors, family history of cancer, parity, and health behaviours. RESULTS: Breast cancer incidence in the cohort was 1.15 times the average in age group 50-59. There was no evidence of depression, trait anxiety, cynical distrust, or coping being significant predictors of breast cancer incidence. CONCLUSION: In this cohort study with the 6-9 year follow-up, psychological factors such as depression, trait anxiety, cynical distrust, or coping did not increase breast cancer risk. [ABSTRACT FROM AUTHOR]

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43-51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have found increased breast cancer risk among female cabin crew. This has been suggested to reflect lifestyle factors (for example, age at first birth), other confounding factors (for example, age at menarche), or occupational factors such as exposure to cosmic radiation and circadian rhythm alterations due to repeated jet lag. Aims: To assess the contribution of occupational versus lifestyle and other factors to breast cancer risk among cabin attendants in Finland. Methods: A standardised self-administered questionnaire on demographic, occupational, and lifestyle factors was given to 1041 cabin attendants. A total of 27 breast cancer cases and 517 non-cases completed the questionnaire. Breast cancer diagnoses were confirmed through the Finnish Cancer Registry. Exposure to cosmic radiation was estimated based on self-reported flight history and timetables. A conditional logistic regression model was used for analysis. Results: In the univariate analysis, family history of breast cancer (OR = 2.67, 95% CI: 1.00 to 7.08) was the strongest determinant of breast cancer. Of occupational exposures, sleep rhythm disruptions (OR = 1.72, 95% Cl: 0.70 to 4.27) were positively related and disruption of menstrual cycles (OR = 0.71, 95% Cl: 0.26 to 1.96) negatively related to breast cancer. However, both associations were statistically non-significant. Cumulative radiation dose (OR = 0.99, 95% Cl: 0.83 to 1.19) showed no effect on breast cancer. Conclusions: Results suggest that breast cancer risk among Finnish cabin attendants is related to well established risk factors of breast cancer, such as family history of breast cancer. There was no clear evidence that the three occupational factors studied affected breast cancer risk among Finnish flight attendants. [ABSTRACT FROM AUTHOR]