Survival after antireflux surgery versus medication in patients with reflux oesophagitis or Barrett's oesophagus: multinational cohort study.

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 per cent) 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.

Invasive and in situ squamous cell carcinoma of the skin: a nationwide study in Iceland.

BACKGROUND: The worldwide incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. OBJECTIVES: To evaluate the tumour burden of in situ and invasive cSCC in Iceland, where the population is exposed to limited ultraviolet radiation. METHODS: This whole-population study used the Icelandic Cancer Registry, which contains records of all in situ and invasive cSCC cases from 1981 to 2017. Incidence of cSCC was evaluated according to age, anatomical location, residence and multiplicity, and trends were assessed using joinpoint analysis. Age-standardized rates (WSR) and age-specific incidence rates per 100 000 person-years were calculated, along with cumulative and lifetime risks. RESULTS: Between 1981 and 2017, in situ cSCC WSR increased from 1·2 to 19·1 for men and from 2·0 to 22·3 for women. Invasive cSCC WSR rose from 4·6 to 14 for men and from 0·3 to 13·2 for women. The average number of in situ cSCC lesions was 1·71 per woman and 1·39 per man. Women developed more in situ cSCCs than invasive cSCCs in almost all anatomical locations, whereas men developed more invasive cSCCs, mostly on the head and neck. The rates of in situ cSCC were higher in Reykjavik compared with rural areas. Furthermore, women more commonly developed multiple in situ lesions. For lip cSCCs, invasive lesions occurred more frequently than in situ lesions among both sexes. Joinpoint analysis showed that in situ cSCC in women exhibited the most rapid incidence increase. CONCLUSIONS: cSCC has become an increasingly significant public health problem in Iceland. Tanning bed use and travelling abroad may contribute to skin cancer development. Public health efforts are needed to stem the behaviours leading to this rapid rise in cSCC.

Occupation and cutaneous melanoma: a 45-year historical cohort study of 14·9 million people in five Nordic countries.

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.

Reintervention or mortality within 90 days of bariatric surgery: population-based cohort study.

BACKGROUND: Bariatric surgery carries a risk of severe postoperative complications, sometimes leading to reinterventions or even death. The incidence and risk factors for reintervention and death within 90 days after bariatric surgery are unclear, and were examined in this study. METHODS: This population-based cohort study included all patients who underwent bariatric surgery in one of the five Nordic countries between 1980 and 2012. Data on surgical and endoscopic procedures, diagnoses and mortality were retrieved from national high-quality and complete registries. Multivariable Cox regression analysis was used to calculate hazard ratios (HRs), adjusted for country, age, sex, co-morbidity, type of surgery and approach, year and hospital volume of bariatric surgery. RESULTS: Of 49 977 patients, 1111 (2·2 per cent) had a reintervention and 95 (0·2 per cent) died within 90 days of bariatric surgery. Risk factors for the composite outcome reintervention/mortality were older age (HR 1·65, 95 per cent c.i. 1·36 to 2·01, for age at least 50 years versus less than 30 years) and co-morbidity (HR 2·66, 1·53 to 4·62, for Charlson co-morbidity index score 2 or more versus 0). The risk of reintervention/mortality was decreased for vertical banded gastroplasty compared with gastric bypass (HR 0·37, 0·28 to 0·48) and more recent surgery (HR 0·51, 0·39 to 0·67, for procedures undertaken in 2010 or later versus before 2000). Sex, surgical approach (laparoscopic versus open) and hospital volume did not influence risk of reintervention/mortality, but laparoscopic surgery was associated with a lower risk of 90-day mortality (HR 0·29, 0·16 to 0·53). CONCLUSION: Reintervention and death were uncommon events within 90 days of bariatric surgery even in this unselected nationwide cohort from five countries. Older patients with co-morbidities have an increased relative risk of these outcomes.

ANTECEDENTES: La cirugía bariátrica conlleva un riesgo de complicaciones postoperatorias graves, que algunas veces ocasionan reintervenciones o incluso son causa de mortalidad. La incidencia y los factores de riesgo de reinterveniones y mortalidad a los 90 días tras cirugía bariátrica no están claros, y fueron examinados en este estudio. MÉTODOS: Todos los pacientes que fueron sometidos a cirugía bariátrica en uno de los cinco países nórdicos en 1980-2012 fueron incluidos en un estudio de cohortes de base poblacional. Los datos de los procedimientos quirúrgicos y endoscópicos, diagnóstico, y mortalidad se obtuvieron a partir de registros nacionales completos y de alta calidad. Mediante una regresión de Cox multivariable se obtuvieron los cocientes de riesgos instantáneos (hazard ratios, HR) y los intervalos de confianza 95% (i.c. del 95%) ajustados por país, edad, sexo, comorbilidad, y tipo, abordaje, año y volumen de casos de cirugía bariátrica del hospital. RESULTADOS: De un total de 49.977 pacientes, 1.111 (2,2%) precisaron una reintervención y 95 (0,2%) fallecieron durante los primeros 90 días tras la cirugía bariátrica. Los factores de riesgo para el resultado compuesto reintervención/mortalidad fueron la edad avanzada (HR = 1,7 (i.c. del 95% 1,4-2,0) edad ≥ 50 versus < 30 años)) y la comorbilidad (HR = 2,7 (i.c. del 95% 1,5-4,6) puntuación del índice de comorbilidad de Charlson ≥ 2 versus 0)). Se observó una disminución de los HRs tras la gastroplastia vertical con banda en comparación con el bypass gástrico (HR = 0,4, (i.c. del 95% 0,3-0,5)) y el periodo de estudio más reciente (HR = 0,5 (i.c. del 95% 0,4-0,7) ≥ 2010 versus < 2000)). El sexo, el abordaje quirúrgico laparoscópico versus abierto y el volumen del hospital no influyeron sobre el riesgo de reintervención/mortalidad, pero la cirugía laparoscópica se asoció con una mortalidad a los 90 días más baja (HR 0,3, i.c. del 95% 0,2-0,5). CONCLUSIÓN: La reintervención y la mortalidad son eventos infrecuentes durante los primeros 90 días tras la cirugía bariátrica, incluso en esta cohorte nacional y no seleccionada de cinco paises. Los pacientes mayores con comorbilidades tienen un riesgo relativo aumentado de reintervención y mortalidad.

Basal cell carcinoma: an emerging epidemic in women in Iceland.

BACKGROUND: An epidemic of basal cell carcinoma (BCC) has led to a significant healthcare burden in white populations. OBJECTIVES: To provide an update on incidence rates and tumour burden in an unselected, geographically isolated population that is exposed to a low level of ultraviolet radiation. METHODS: This was a whole-population study using a cancer registry containing records of all cases of BCC in 1981-2017. We assessed BCC incidence according to age, residence and multiplicity and assessed trends using join-point analysis. Age-standardized and age-specific incidence rates were calculated along with cumulative and lifetime risks. RESULTS: During the study period, the age-standardized incidence rates increased from 25·7 to 59·9 for men, and from 22·2 to 83·1 for women (per 100 000). Compared with the single-tumour burden, the total tumour burden in the population was 1·72 times higher when accounting for multiplicity. At the beginning of the study period, the world-standardized rates in men and women were similar, but by the end of the study period the rates were 39% higher in women (83·1 per 100 000, 95% confidence interval 77·9-88·3) than in men (59·9 per 100 000, 95% confidence interval 55·6-64·2). This increase was most prominent in women on sites that are normally not exposed to ultraviolet radiation in Iceland: the trunk and legs. CONCLUSIONS: This is the only reported population in which the incidence of BCC is significantly higher in women than in men. The period of notable increase in BCC lesions correlates with the period of an increase in tanning beds and travel popularity. The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought. What is already known about this topic? Basal cell carcinoma (BCC) is becoming an increasing healthcare burden worldwide, especially in white populations. Recent population studies have reported a rapid increase in incidence among younger individuals, especially women. What does this study add? Iceland is the only reported population in which the incidence of BCC is significantly higher in women than in men, and there does not seem to be a clear relationship between latitude and BCC incidence in Europe. Men might be comparatively protected in the northern low-ultraviolet environment, with tanning beds and travel abroad likely playing important roles in the observed incidence increase, especially in women. The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought. Linked Comment: Pandeya. Br J Dermatol 2020; 183:799-800.

Electronically ascertained extended pedigrees in breast cancer genetic counseling.

A comprehensive pedigree, usually provided by the counselee and verified by medical records, is essential for risk assessment in cancer genetic counseling. Collecting the relevant information is time-consuming and sometimes impossible. We studied the use of electronically ascertained pedigrees (EGP). The study group comprised women (n = 1352) receiving HBOC genetic counseling between December 2006 and December 2016 at Landspitali in Iceland. EGP's were ascertained using information from the population-based Genealogy Database and Icelandic Cancer Registry. The likelihood of being positive for the Icelandic founder BRCA2 pathogenic variant NM_000059.3:c.767_771delCAAAT was calculated using the risk assessment program Boadicea. We used this unique data to estimate the optimal size of pedigrees, e.g., those that best balance the accuracy of risk assessment using Boadicea and cost of ascertainment. Sub-groups of randomly selected 104 positive and 105 negative women for the founder BRCA2 PV were formed and Receiver Operating Characteristics curves compared for efficiency of PV prediction with a Boadicea score. The optimal pedigree size included 3° relatives or up to five generations with an average no. of 53.8 individuals (range 9-220) (AUC 0.801). Adding 4° relatives did not improve the outcome. Pedigrees including 3° relatives are difficult and sometimes impossible to generate with conventional methods. Pedigrees ascertained with data from pre-existing genealogy databases and cancer registries can save effort and contain more information than traditional pedigrees. Genetic services should consider generating EGP's which requires access to an accurate genealogy database and cancer registry. Local data protection laws and regulations have to be addressed.

Trends in incidence of thick, thin and in situ melanoma in Europe.

BACKGROUND: We analysed trends in incidence for in situ and invasive melanoma in some European countries during the period 1995-2012, stratifying for lesion thickness. MATERIAL AND METHODS: Individual anonymised data from population-based European cancer registries (CRs) were collected and combined in a common database, including information on age, sex, year of diagnosis, histological type, tumour location, behaviour (invasive, in situ) and lesion thickness. Mortality data were retrieved from the publicly available World Health Organization database. RESULTS: Our database covered a population of over 117 million inhabitants and included about 415,000 skin lesions, recorded by 18 European CRs (7 of them with national coverage). During the 1995-2012 period, we observed a statistically significant increase in incidence for both invasive (average annual percent change (AAPC) 4.0% men; 3.0% women) and in situ (AAPC 7.7% men; 6.2% women) cases. DISCUSSION: The increase in invasive lesions seemed mainly driven by thin melanomas (AAPC 10% men; 8.3% women). The incidence of thick melanomas also increased, although more slowly in recent years. Correction for lesions of unknown thickness enhanced the differences between thin and thick cases and flattened the trends. Incidence trends varied considerably across registries, but only Netherlands presented a marked increase above the boundaries of a funnel plot that weighted estimates by their precision. Mortality from invasive melanoma has continued to increase in Norway, Iceland (but only for elder people), the Netherlands and Slovenia.

Incidence and occupational variation of ovarian granulosa cell tumours in Finland, Iceland, Norway and Sweden during 1953-2012: a longitudinal cohort study.

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.

Familial risk of non-Hodgkin lymphoma by sex, relationship, age at diagnosis and histology: a joint study from five Nordic countries.

We aimed to estimate stratified absolute (cumulative) and relative (standardized incidence ratios; SIRs) risks of non-Hodgkin lymphoma (NHL) in relatives of NHL patients. A cohort of 169 830 first-degree relatives of 45 406 NHL patients who were diagnosed between 1955 and 2010 in five European countries was followed for cancer incidence. The lifetime (0-79 year) cumulative risk of NHL in siblings of a patient with NHL was 1.6%, which represents a 1.6-fold increased risk (SIR=1.6, 95% confidence interval (CI)=1.2-1.9) over the general population risk. NHL risk among parent-offspring pairs was increased up to 1.4-fold (95% CI=1.3-1.5; lifetime risk 1.4%). The lifetime risk was higher when NHL was diagnosed in a sister (2.5% in her brothers and 1.9% in her sisters) or a father (1.7% in his son). When there were ⩾2 NHL patients diagnosed in a family, the lifetime NHL risk for relatives was 2.1%. Depending on sex and age at diagnosis, twins had a 3.1-12.9% lifetime risk of NHL. Family history of most of the histological subtypes of NHL increased the risk of concordant and some discordant subtypes. Familial risk did not significantly change by age at diagnosis of NHL in relatives. Familial risk of NHL was not limited to early onset cases.

Completeness and timeliness: Cancer registries could/should improve their performance.

UNLABELLED: Cancer registries must provide complete and reliable incidence information with the shortest possible delay for use in studies such as comparability, clustering, cancer in the elderly and adequacy of cancer surveillance. Methods of varying complexity are available to registries for monitoring completeness and timeliness. We wished to know which methods are currently in use among cancer registries, and to compare the results of our findings to those of a survey carried out in 2006. METHODS: In the framework of the EUROCOURSE project, and to prepare cancer registries for participation in the ERA-net scheme, we launched a survey on the methods used to assess completeness, and also on the timeliness and methods of dissemination of results by registries. We sent the questionnaire to all general registries (GCRs) and specialised registries (SCRs) active in Europe and within the European Network of Cancer Registries (ENCR). RESULTS: With a response rate of 66% among GCRs and 59% among SCRs, we obtained data for analysis from 116 registries with a population coverage of ∼280 million. The most common methods used were comparison of trends (79%) and mortality/incidence ratios (more than 60%). More complex methods were used less commonly: capture-recapture by 30%, flow method by 18% and death certificate notification (DCN) methods with the Ajiki formula by 9%. The median latency for completion of ascertainment of incidence was 18 months. Additional time required for dissemination was of the order of 3-6 months, depending on the method: print or electronic. One fifth (21%) did not publish results for their own registry but only as a contribution to larger national or international data repositories and publications; this introduced a further delay in the availability of data. CONCLUSIONS: Cancer registries should improve the practice of measuring their completeness regularly and should move from traditional to more quantitative methods. This could also have implications in the timeliness of data publication.

Cutaneous melanoma in Iceland: changing Breslow's tumour thickness.

BACKGROUND: The incidence of cutaneous melanoma increased dramatically in Iceland during the last two decades of the 20th century. OBJECTIVE: The aim of this study was to investigate the trend in Breslow's tumour thickness during the years 1980-2009. METHODS: The population-based Icelandic Cancer Registry provided information on all cutaneous melanomas diagnosed in the country during the study period, a total of 854 cases. Incidence rates were stratified according to gender, age at diagnosis, year of diagnosis and Breslow's tumour thickness. RESULTS: When stratified by gender and age, the incidence of thin (≤1.0 mm) melanomas increased dramatically in all subgroups. The increase in thin (≤1.0 mm) melanomas was more apparent in women or 2.6 per 100,000 in 1980-1989 to 13.3 in 2000-2009 and especially in young (<50 years) women or from 1.6 to 12.2 per 100,000 during the same period compared to an increase from 0.2 to 3.4 per 100,000 for young (<50 years) men (P < 0.05). In intermediate thickness (1.01-4.0 mm) tumours, the incidence increased only in men over the age of 50 from 2.1 in 1980-1989 to 11.3 per 100,000 in 2000-2009 (P < 0.05). The incidence of thick melanomas (>4 mm) did not increase. The median Breslow's thickness declined from 2.15 mm in 1980-1989 to 0.9 mm in 2000-2009 in males and from 1.0 to 0.6 mm in females for the same period (P < 0.001). CONCLUSION: The rise in melanoma incidence in individuals under 50 years and in women over 50 years was confined to thin tumours. However, among older males there was also an increased incidence of tumours of an intermediate thickness. This could indicate that future melanoma educational campaigns in Iceland should be directed at older individuals, and that older men may need special attention regarding suspicious nevi.

Trends in incidence and predictions of cutaneous melanoma across Europe up to 2015.

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.

Occupation and risk of primary fallopian tube carcinoma in Nordic countries.

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.

Effects of occupation on risks of avoidable cancers in the Nordic countries.

Knowledge of cancer risk according to occupational affiliation is an essential part of formatting preventive actions aimed at the adult population. Herein, data on 10 major cancer sites amenable by life style exposures from the Nordic Occupational Cancer Study (NOCCA) are presented. All subjects aged 30-64 years participating in one or more national censuses in Denmark, Finland, Iceland, Norway, or Sweden between 1960 and 1990 were included in the cohort and followed up for cancer from inclusion until 2003/2005 via a linkage with the national cancer registries, and standardised incidence ratios (SIRs) were computed. Variation in risk across occupations was generally larger in men than in women. In men, the most consistent cluster with high risk of numerous cancer types included waiters, cooks and stewards, beverage workers, seamen, and chimney sweeps. Two clusters of occupations with generally low cancer risks were seen in both men and women. The first one comprised farmers, gardeners, and forestry workers, the second one included groups with high education, specifically those in health and pedagogical work. Although cancer risk varies by occupation, only a smaller part of the variation can be attributed to occupational exposures in the strict sense. Preventive measures at the work place are important to avoid established and new occupational health hazards. This study also indicates that the work place in addition should be seen as a useful arena for reaching groups of adults with more or less similar habits and attitudes for general health promotion.

Familial risks in nervous system tumours: joint Nordic study.

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.

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions.

Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).

A case-control study to estimate the impact of the Icelandic population-based mammography screening program on breast cancer death.

BACKGROUND: The Icelandic breast cancer screening program, initiated November 1987 in Reykjavik and covering the whole country from December 1989, comprises biennial invitation to mammography for women aged 40-69 years old. PURPOSE: To estimate the impact of mammography service screening in Iceland on deaths from breast cancer. MATERIAL AND METHODS: Cases were deaths from breast cancer from 1990 onwards in women aged 40 and over at diagnosis, during the period November 1987 to December 31, 2002. Age- and screening-area-matched, population-based controls were women who had also been invited to screening but were alive at the time their case died. RESULTS: Using conditional logistic regression on the data from 226 cases and 902 controls, the odds ratio for the risk of death from breast cancer in those attending at least one screen compared to those never screened was 0.59 (95% CI 0.41-0.84). After adjustment for healthy-volunteer bias and screening-opportunity bias, the odds ratio was 0.65 (95% CI 0.39-1.09). CONCLUSION: These results indicate a 35-40% reduction in breast cancer deaths by attending the Icelandic breast cancer screening program. These results are consistent with the overall evidence from other observational evaluations of mammography-based programs.

Adenocarcinoma of the prostate in Iceland: a population-based study of stage, Gleason grade, treatment and long-term survival in males diagnosed between 1983 and 1987.

OBJECTIVE: To investigate adenocarcinoma of the prostate in a single population with an extended follow-up period. MATERIAL AND METHODS: Using the Icelandic Cancer Registry, we identified all Icelandic men diagnosed with prostate cancer between 1983 and 1987. Disease stage, initial treatment and follow-up information were obtained from hospital records and death certificates. A critical evaluation was made of the accuracy of the death certificates regarding prostate cancer. All available histology information was reviewed and graded according to the Gleason grading system. RESULTS: A total of 414 men were diagnosed with adenocarcinoma of the prostate. Of these, 370 were alive at the time of diagnosis and stage could be determined. Four stage groups were defined: focal incidental (n=50); localized (n=164); local advanced (n=32); and metastatic disease (n=124). The mean age at diagnosis was 74.4 years (range 53-94 years). The combined Gleason score was 2-5 in 89, 6-7 in 117, 8-10 in 117 and unknown in 47 cases. The median follow-up period for the group was 6.15 years (range 0.3-19.8 years). Thirty men received treatment with curative intent: radiation therapy, n=20; and radical prostatectomy, n=10. A total of 334 patients died during the follow-up period, of whom 168 (50%) died of prostate cancer. Prostate cancer-specific survival at 10 and 15 years was 100% and 90.6%, respectively for focal incidental cancer; 73.1% and 60.8% for men with localized disease; 23.4% and 11.7% for local advanced disease; and 6.81% and 5.45% for metastatic disease. A Cox multivariate analysis showed age, stage and Gleason score to be independent predictors of prostate cancer death. A total of 104 patients with localized disease and a Gleason score of

Positive association between plasma antioxidant capacity and n-3 PUFA in red blood cells from women.

PUFA are susceptible to oxidation. However, the chain-reaction of lipid peroxidation can be interrupted by antioxidants. Whether an increased concentration of PUFA in the body leads to decreased antioxidant capacity and/or increased consumption of antioxidants is not known. To elucidate the relationship between plasma total antioxidant capacity (TAC), the concentration of antioxidant vitamins, and the proportion of PUFA in red blood cells (RBC), plasma TAC was measured by a Trolox equivalent antioxidant capacity assay in blood samples from 99 Icelandic women. Concentrations of tocopherols and carotenoids in the plasma were determined by HPLC, and the FA composition of RBC total lipids was analyzed by GC. Plasma TAC and the plasma concentration of alpha-tocopherol correlated positively with the proportion of total n-3 PUFA, 20:5n-3, and 22:6n-3 in RBC, whereas the plasma lycopene concentration correlated negatively with the proportion of total n-3 PUFA and 20:5n-3. On the other hand, plasma TAC correlated negatively with the proportion of n-6 PUFA in RBC. Plasma TAC also correlated positively with the plasma concentration of alpha-tocopherol, alcohol consumption, and age. Both the plasma concentration of alpha-tocopherol and age correlated positively with the proportion of n-3 PUFA in RBC; however, n-3 PUFA contributed independently to the correlation with plasma TAC. Because the proportion of n-3 PUFA in RBC reflects the consumption of n-3 PUFA, these results suggest that dietary n-3 PUFA do not have adverse effects on plasma TAC or the plasma concentration of most antioxidant vitamins.