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Kristjan Sigurdsson,1,3 Elínborg Jóna Ólafsdóttir,21The Icelandic Cancer Detection Clinic, 2The Icelandic Cancer Registry, Icelandic Cancer Society, 3Faculty of Medicine, University of Iceland, Reykjavik, IcelandObjective: This study analyzes the efficacy of the Icelandic population-based service mammography screening.Material and methods: Women aged 40–69 were invited for screening at 2-year intervals starting in November 1987. The study evaluates: (A) attendance and other screened performance parameters during 1998–2010; (B) trends in age-standardized and age-specific incidence rates during 1969–2010 and mortality rates during 1969–2010; and (C) distribution of risk factors and disease specific death rates according to mode of detection.Results: (A) In the age group of 40–69, the average 2-year attendance was 62%, recall rate was 4.1%, needle biopsy rate was 1.3%, surgery rate was 0.6%, invasive cancer rate was 0.4%, and ductal carcinoma in situ (DCIS) rate was 0.06%. (B) The linear incidence trend after the start of screening decreased significantly in the age group 40–49, increased significantly in the age group 50–69, but decreased non-significantly in the age group 70–79. The decreased age-specific incidence in the 70–79 age group was, however, greater than the increased age-specific incidence at the ages 50–69. The mortality rate decreased 41% for all age groups and the linear mortality trend decreased significantly at ages 40–49, 50–69, and 70–79. In the age group 40–74 years, the age-specific mortality decreased by 6.9 cases per 2000 during a 10-year period. (C) Screen-detected women had significantly smaller tumors, more favorable tumor grade, fewer axillary metastases and, after correction for other risk factors, the likelihood of dying from cancer decreased 54% (hazard ratio: 0.46; 95% confidence interval: 0.31–0.69) for these patients compared to cases of nonparticipators.Conclusion: The study results confirm acceptable rates of recalls and referrals for further diagnosis and treatment, and significantly decreased breast cancer mortality rate after starting screening.Keywords: mammography, screening, breast cancer, mortality, incidence, mode of detection, risk factors

Introduction: The Icelandic Cancer Registry (ICR) was founded seventy years ago by the Icelandic Cancer Society. In 2007 the ICR became one of the health registers of the Directorate of Health. In this paper we present cancer incidence, mortality, and survival in Iceland over 70 years., Material and Methods: The ICR receives information on cancer diagnoses from histopathological laboratories, the Hospital Discharge Registry and the Cause of Death Registry. Iceland participates in the Nordic cancer database NORDCAN. Because of the small population size, random variation in numbers is very prominent. Therefore, data from ICR are published as five-year averages., Results: For all malignancies combined, age-standardized incidence (ASI) in men rose steadily until around 15 years ago when a decline started. This is in line with prostate- and lung cancer incidence trends. In women, the ASI was lower than in men, but it is still on the rise despite declining lung cancer incidence. ASI for breast cancer, the most common cancer in women, is increasing. Simultaneously, cancer mortality for both sexes has declined in recent years and cancer survival is improving., Conclusions: Population-based cancer registration for over 70 years makes it possible to monitor the epidemiology of cancer in Iceland and compare with other countries. The changes in trends in ASI are in line with changes of cancer risk factors and diagnostic policy. The decline in cancer mortality and improvement in survival reflects advances in cancer treatment as well as effects of early detection and prevention.

Background: Keratinocyte carcinoma (KC) is the commonest type of malignancy in humans; however, the impact of KC on survival is poorly understood., Objectives: This study characterizes the impact of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and squamous cell carcinoma in situ (SCCis) on the survival of Icelanders., Methods: This whole population study evaluated relative survival of KC in Iceland by using a cancer registry containing records of all BCC, SCCis, and SCC cases recorded in Iceland between 1981 and 2015., Results: Between 1981 and 2015, 8767 Icelanders were diagnosed with their first localized KC. A total of 6473 individuals with BCC, 1194 with SCCis, and 1100 with invasive SCC, respectively. BCC was not associated with decreased survival except for men diagnosed with BCC between 1981 and 1995 for whom decreased 10-year relative survival was observed (85.3, 95% CI [77.9-92.7]). SCC and SCCis were both associated with a decrease in relative survival for certain population subgroups such as individuals <50 years of age at time of diagnosis., Conclusion: Our whole population cohort survival study examining the Icelandic Cancer Registry supports prior studies demonstrating that BCC is not associated with a reduction in relative survival and that SCC and SCCis are associated with comparatively poor relative survival in certain population subgroups., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Worldwide, the health-promoting effects of breastfeeding on children and their mothers are indisputable. The frequency and duration of breastfeeding varies greatly internationally but studies on prevalence and influencing factors of breastfeeding in Iceland are scanty and the published ones deal with small groups. The aim of this research is to describe the epidemiology of breastfeeding duration and its influencing factors in Iceland among a large cohort in a whole population over almost one century., Material and Methods: This is a historical cohort study, using data from The Cancer Detection Clinic Cohort of The Icelandic Cancer Society, collected retrospectively by questionnaires during the years 1964-2008. The data consisted of mothers´ reported information on breastfeeding of their 81,889 children, 36,537 first-borns and 45,352 younger siblings. The frequency and duration of breastfeeding was calculated and the effects of the following exposure variables were assessed: Maternal age, BMI (N=4950, data collected 1979-2008) and smoking (N=32.087, data collected 1995-2008), the child's year of birth and its order in the sibling group., Results: The children were born in the period of 1917-2008. In the late 1970s, the average duration of breastfeeding began to increase, in all age groups of mothers, increasing rapidly from 3 months to 7-8 months. At about the same time, the breastfeeding duration increased depending on the birth order of the children, younger children were breastfed for longer than their older siblings. Women with normal weight (BMI 18.5 to 24.9) breastfed their babies the longest, while obese women breastfed the shortest. Women with any history of smoking reported shorter duration of breastfeeding than women who had never smoked., Conclusion: The increase in the average duration of breastfeeding in Iceland a few decades ago is in accordance with the information in the World Health Organization's database from European countries 1975-2000, where the Nordic countries and most Northern European countries promoted breastfeeding at a similar time. High BMI and maternal smoking are important variables when studying breastfeeding and this study indicates their negative association with the duration of breastfeeding.

Estrogen receptor-positive (ER+) breast cancer generally confers a more favorable prognosis than ER-negative cancer, however, a different picture is emerging for BRCA2 mutation carriers and young patients. We used nationwide data from population-based registries to study prognostic effects in those two groups. Of all 2817 eligible women diagnosed with breast cancer in Iceland during 1980-2004, 85% had been tested for the Icelandic 999del5 BRCA2 (c.771&#95;775delTCAAA) founder pathogenic variant. We compared breast cancer-specific survival, effects of ER status, other clinical parameters, and treatment, between three mutually exclusive groups: BRCA2-carriers, non-carriers diagnosed 40 years or younger, and older non-carriers. Prevalence of the BRCA2 mutation among tested patients <=40 years of age was 21.0%, but it was 5.4% among women diagnosed >40 years of age. For ER+ cancer, breast cancer-specific 15-year survival was 49.7%, 55.2%, and 74.7%, among BRCA2-carriers, young and older non-carriers, respectively, whereas for ER-negative cancer, survival was similar (64.0-69.3%) for all three groups. Neither BRCA2 carriers nor young non-carriers did tumor grade 3 predict worse survival than did tumor grade 1. The adverse outcome for the young cases cannot be explained by BRCA2 mutations, as carriers were excluded from the group. Those two clinically important patient groups need special attention with respect to treatment choices, in particular, if diagnosed with ER+ tumors. It is thus advisable to have knowledge of BRCA2 status when treatment decisions are made. Finally, it is important to understand the biological basis for the specific nature of ER+ tumors in young women and BRCA2 carriers., (© 2023. The Author(s).)

Aim of the Article: We present our new GDPR-compliant federated analysis programme (nordcan.R), how it is used to compute statistics for the Nordic cancer statistics web platform NORDCAN, and demonstrate that it works also with non-Nordic data., Materials and Methods: We chose R and Stata programming languages for writing nordcan.R. Additionally, the internationally used CRG Tools programme by International Agency for Research on Cancer (IARC/WHO) was employed. A formal assessment of (GDPR-compliant) anonymity of all nordcan.R outputs was performed. In order to demonstrate that nordcan.R also works with non-Nordic data, we used data from the Netherlands Cancer Registry., Results: nordcan.R, publicly available on Github, takes as input cancer and general population data and produces tables of statistics. Each NORDCAN participant runs nordcan.R locally and delivers its results to IARC for publication. According to our anonymity assessment the data can be shared with international organizations, including IARC. nordcan.R incidence results on Norwegian and Dutch data are highly similar to those produced by two other independent methods., Conclusion: nordcan.R produces accurate cancer statistics where all personal and sensitive data are kept within each cancer registry. In the age of strict data protection policies, we have shown that international collaboration in cancer registry research and statistics reporting is achievable with the federated analysis approach. Undertakings similar to NORDCAN should consider using nordcan.R., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor LV declared a past co-authorship with the author TB., (Copyright © 2023 Larønningen, Skog, Engholm, Ferlay, Johannesen, Kristiansen, Knoors, Kønig, Olafsdottir, Pejicic, Pettersson, Skovlund, Storm, Tian, Aagnes and Miettinen.)

Purpose:  Liver elastography is increasingly being applied in screening for and follow-up of pediatric liver disease, and has been shown to correlate well with fibrosis staging through liver biopsy. Because time is of the essence when examining children, we wanted to evaluate if a reliable result can be achieved with fewer acquisitions., Materials and Methods:  243 healthy children aged 4-17 years were examined after three hours of fasting. Participants were divided into four age groups: 4-7 years; 8-11 years; 12-14 years and 15-17 years. Both two-dimensional shear wave elastography (2D-SWE; GE Logiq E9) and point shear wave elastography (pSWE; Samsung RS80A with Prestige) were performed in all participants, while transient elastography (TE, Fibroscan) was performed in a subset of 87 children aged 8-17 years. Median liver stiffness measurement (LSM) values of 3, 4, 5, 6, 7, and 8 acquisitions were compared with the median value of 10 acquisitions (reference standard). Comparison was performed for all participants together as well as within every specific age group. We investigated both the intraclass correlation coefficient (ICC) with absolute agreement and all outliers more than 10 %, 20 % or ≥ 0.5 or 1.0 kPa from the median of 10 acquisitions., Results:  For all three systems there was no significant difference between three and ten acquisitions, with ICCs ≥ 0.97. All systems needed 4 acquisitions to achieve no LSM deviating ≥ 1.0 kPa of a median of ten. To achieve no LSM deviating ≥ 20 % of a median of ten acquisitions, pSWE and TE needed 4 acquisitions, while 2D-SWE required 6 acquisitions., Conclusion:  Our results contradict recommendations of 10 acquisitions for pSWE and TE and only 3 for 2D-SWE., Competing Interests: OHG did consultancy for GE and Samsung in 2017., (Thieme. All rights reserved.)

In this article the incidence and mortality for cancer of the colon and rectum in Iceland is discussed. The two most common screening methods, faecal immunochemical test (FIT) and colonoscopy are compared and an estimate of cost and benefits for the Icelandic society will be made. The incidence of cancer of the colon and rectum has been increasing in Iceland in last decades but mortality has decreased and survival improved. However, more individuals die from cancer of the colon and rectum than from both breast- and cervical cancer added together. It is likely that screening for cancer of the colon and rectum, could prevent at least 6 of the 28 deaths related to those cancers, occurring yearly in Iceland in screening age, given a screening ages of 50-74 years. The extra cost for the Icelandic community due to the implementation of screening for cancer of the colon and rectum will be acceptable due to the lower cost of simpler treatments, lower cancer incidence and reduced mortality.

Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Background: The natural history of breast cancer among BRCA2 carriers has not been clearly established. In a previous study from Iceland, positive ER status was a negative prognostic factor. We sought to identify factors that predicted survival after invasive breast cancer in an expanded cohort of BRCA2 carriers., Methods: We studied 608 women with invasive breast cancer and a pathogenic BRCA2 mutation (variant) from four Nordic countries. Information on prognostic factors and treatment was retrieved from health records and by analysis of archived tissue specimens. Hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression., Results: About 77% of cancers were ER-positive, with the highest proportion (83%) in patients under 40 years. ER-positive breast cancers were more likely to be node-positive (59%) than ER-negative cancers (34%) (P < 0.001). The survival analysis included 584 patients. Positive ER status was protective in the first 5 years from diagnosis (multivariate HR = 0.49; 95% CI 0.26-0.93, P = 0.03); thereafter, the effect was adverse (HR = 1.91; 95% CI 1.07-3.39, P = 0.03). The adverse effect of positive ER status was limited to women who did not undergo endocrine treatment (HR = 2.36; 95% CI 1.26-4.44, P = 0.01) and patients with intact ovaries (HR = 1.99; 95% CI 1.11-3.59, P = 0.02)., Conclusions: The adverse effect of a positive ER status in BRCA2 carriers with breast cancer may be contingent on exposure to ovarian hormones.

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970-2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age-standardized incidence and mortality, relative, cancer-specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970-1978 and 1997-2004), 5-year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage-stratified, improved 5-year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1-year survival was mainly observed in stages III and IV. Five-year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1-year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland., (© 2017 UICC.)

Purpose: Breast cancer associated with estrogen-progestin (EP) therapy may have more favorable characteristics than cancer in never users, but results are conflicting. It is not well known either whether Body Mass Index (BMI) modifies this association. We investigated breast cancer characteristics in EP users for lean (BMI < 25 kg/m 2 ) and overweight women (BMI ≥ 25 kg/m 2 )., Methods: The Icelandic Cancer Detection Clinic cohort, with information on breast cancer risk factors for 90% of Icelandic women, was linked with the population-based Icelandic Cancer Registry. A total of 781 women with invasive breast cancer diagnosed 51 years or older were matched with 7761 controls from the cohort. Conditional logistic regression was used for estimating adjusted odds ratios (OR) and 95% confidence intervals (CI) according to tumor characteristics, stratified by BMI. Polytomous logistic regression was applied in a case-only analysis for testing whether the risk associated with EP use differed according to tumor characteristics., Results: Ever EP users had a twofold higher risk of breast cancer compared with never users (OR 2.05, 95% CI 1.71-2.45). In lean women, EP use was significantly less likely to be associated with grade 2 or 3 tumors than grade 1 tumors, contrary to overweight women for whom risk was increased irrespective of grade. EP use in overweight women was associated with a higher risk of lobular than ductal cancer (OR 2.75, 95% CI 1.29-5.87)., Conclusion: Among lean EP users, tumor characteristics were more favorable than among never users. This effect was not observed for overweight women.

Background: The impact of an inherited BRCA2 mutation on the prognosis of women with breast cancer has not been well documented. We studied the effects of oestrogen receptor (ER) status, other prognostic factors and treatments on survival in a large cohort of BRCA2 mutation carriers., Methods: We identified 285 breast cancer patients with a 999del5 BRCA2 mutation and matched them with 570 non-carrier patients. Clinical information was abstracted from patient charts and pathology records and supplemented by evaluation of tumour grade and ER status using archived tissue specimens. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. The effects of various therapies were studied in patients treated from 1980 to 2012., Results: Among mutation carriers, positive ER status was associated with higher risk of death than negative ER status (HR=1.94; 95% CI=1.22-3.07, P=0.005). The reverse association was seen for non-carriers (HR=0.71; 95% CI: 0.51-0.97; P=0.03)., Conclusions: Among BRCA2 carriers, ER-positive status is an adverse prognostic factor. BRCA2 carrier status should be known at the time when treatment decisions are made.

Objectives: A novel automated 3-dimensional (3D) sonographic method has been developed for measuring gastric volumes. This study aimed to validate and assess the reliability of this novel 3D sonographic method compared to the reference standard in 3D gastric sonography: freehand magneto-based 3D sonography., Methods: A prospective study with 8 balloons (in vitro) and 16 stomachs of healthy volunteers (in vivo) was performed. After a 500-mL liquid meal, 1 preprandial and 3 postprandial volume scans of the stomachs were performed by the novel 3D sonographic method and the current reference-standard 3D sonographic method., Results: The in vitro study showed a mean volume difference between the novel method and the true balloon volume of -1.3 mL; limits of agreement (LoA) were small (-39.3 to12.3 mL), with an intraclass correlation coefficient (ICC) of 0.998. The in vivo study showed a mean gastric volume of 321 mL between the novel method and the freehand magneto-based method, with a mean volume difference of -4.4 mL; LoA were -40.1 to 31.2 mL, and the ICC was 0.991. The intraobserver and interobserver variability rates were low, at 0.8 mL (LoA, -24.0 to 25.6 mL), with an ICC of 0.995, and 0.5 mL (LoA, of -26.8 to 27.8 mL), with an ICC of 0.999, respectively., Conclusions: The novel 3D sonographic method with automated acquisition showed good agreement with the current reference-standard gastric 3D sonographic method, with low intraobserver and interobserver variability. This novel 3D sonographic method is a valid and reliable technique for determining gastric accommodation.

Background: Norway introduced newborn screening for cystic fibrosis (CF) March 1, 2012. We present results from the first three years of the national newborn CF screening program., Methods: Positive primary screening of immunoreactive trypsinogen (IRT) was followed by DNA testing of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. Infants with two CFTR mutations were reported for diagnostic follow-up., Results: Of 181,859 infants tested, 1454 samples (0.80%) were assessed for CFTR mutations. Forty children (1:4546) had two CFTR mutations, of which only 21 (1:8660) were confirmed to have a CF diagnosis. The CFTR mutations differed from previously clinically diagnosed CF patients, and p.R117H outnumbered p.F508del as the most frequent mutation. One child with a negative IRT screening test was later clinically diagnosed with CF., Conclusions: The CF screening program identified fewer children with a conclusive CF diagnosis than expected. Our data suggest a revision of the IRT/DNA protocol., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is an aggressive variant of PTC that is believed to have worse outcomes than classical PTC. The objective of this study was to investigate the incidence, survival, and disease recurrence of patients with TCV and compare them with other PTC in a whole population., Methods: Information on all thyroid carcinomas diagnosed in Iceland from 1990 to 2009 was obtained from the Icelandic Cancer Registry. PTC diagnosed postmortem was excluded. The date of diagnosis, sex, and age at diagnosis were registered. All histopathology material was re-evaluated, and papillary thyroid tumors classified as either TCV or other types of PTC. Tumors were classified as TCV if >50% of cells were tall (height > twice the width). TNM stage was determined for all the cases. Endpoints were thyroid cancer-specific death and thyroid cancer recurrence., Results: Out of 376 patients diagnosed with PTC in the study period, 49 (13%) were classified as TCV. Patients with TCV were older (66 years vs. 49 years, p<0.001), more often had pT4 tumors (71% vs. 15%, p<0.001), had higher rates of nodal metastasis (51% vs. 22%, p<0.001), and more often distant metastasis (14% vs. 2%, p<0.001). The age-adjusted incidence of TCV for men was 0.5/100,000 [confidence interval (CI) 0.3-0.7] and for women 0.7/100,000 [CI 0.4-1.0] between 1990 and 2009. The five-year disease-specific survival for TCV was 83% [CI 68-91] compared to 98% [CI 96-99] for other PTC respectively (p<0.001). In multivariate analysis, TCV histology was an independent risk factor for recurrence (hazard ratio (HR) 3.18 [CI 1.48-6.84]) but not for disease specific survival (HR 1.86 [CI 0.77-4.73])., Conclusions: TCV comprises 13% of all diagnosed PTC in Iceland with an incidence of 0.5/100,000 for men and 0.7/100,000 for women. Patients diagnosed with TCV have worse five-year disease-specific survival than patients with other PTC. TCV histology is an independent risk factor for disease recurrence but not for disease-specific survival.

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., (© 2014 European Academy of Dermatology and Venereology.)

Background: Findings on potential interactive effects of oral contraceptives (OCs) and hormone replacement therapy (HRT) on breast cancer risk have been inconsistent. We aimed to use population-based cohort data to determine whether former use of OCs affects breast cancer risk among HRT users, taking into account regimens of HRT, duration and currency of use., Methods: The cohort consisted of 16 928 Icelandic women who visited the Icelandic Cancer Detection Clinic in 1979-2006 and provided information on use of OCs and HRT when they were 48 years or older. By record linkage to the Icelandic Cancer Registry, all breast cancer diagnosed during follow-up was identified. Using Cox regression, hazard ratios (HRs) for breast cancer according to hormone use were estimated, adjusting for menstrual and reproductive risk factors. Also, interaction analyses were carried out., Results: Breast cancer risk was significantly increased among ever users of combined estrogen and progestin (EP-HRT) preparations (HR=2.61; 95% CI 2.00-3.41) and not among users of estrogen-only regimens (E-only HRT) (HR=1.13; 95% CI 0.85-1.49). Ever users of both OCs and HRT had higher breast cancer risk than users of only one of the two (HR=2.19; 95% CI 1.67-2.87). After restricting the analysis to EP-HRT and focusing on long-term and current use, there was an indication of a negative interaction with ever OC use (p=0.06); HR=2.87; 95% CI 1.79-4.60 for never OC users and HR=2.24; 95% CI 1.51-3.34 for former OC users., Conclusion: After taking HRT regimen, duration and currency of use into account, the results of our population-based cohort study do not support the notion that former OC use increases breast cancer risk among HRT users, on the contrary there was an indication of a slightly lower risk in former OC users, restricted to current, long-term EP-HRT users.

Available data correlating symptoms of colon cancer patients with the severity of the disease are very limited. In a population-based setting, we correlated information on symptoms of colon cancer patients with several pathological tumor parameters and survival. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 for this retrospective, population-based study was obtained from the Icelandic Cancer Registry. Information on symptoms of patients and blood hemoglobin was collected from patients' files. Pathological parameters were obtained from a previously performed standardized tumor review. A total of 768 patients entered this study; the median age was 73 years. Tumors in patients presenting at diagnosis with visible blood in stools were significantly more likely to be of lower grade, having pushing border, conspicuous peritumoral lymphocytic infiltration, and lower frequency of vessel invasion. Patients with abdominal pain and anemia were significantly more likely to have vessel invasion. Logistic regression showed that visible blood in stools was significantly associated with protecting pathological factors (OR range 0.38-0.83, p < 0.05). Tumors in patients presenting with abdominal pain were strongly associated with infiltrative margin and scarce peritumoral lymphocytic infiltration (OR = 1.95; 2.18 respectively, p < 0.05). Changes in bowel habits were strongly associated with vessel invasion (OR = 2.03, p < 0.05). Cox regression showed that blood in stools predicted survival (HR = 0.54). In conclusion, visible blood in stools correlates significantly with all the beneficial pathological parameters analyzed and with better survival of patients. Anemia, general symptoms, changes in bowel habits, acute symptoms, and abdominal pain correlate with more aggressive tumor characteristics and adverse outcome for patients., (© 2013 APMIS Published by Blackwell Publishing Ltd.)

It is not well known to what extent carrying a BRCA2 mutation affects the survival of women with breast cancer and prognostic factors among BRCA2-positive women warrant investigation. Using a record linkage approach we compared the long-term survival in carriers and noncarriers of an inherited BRCA2 founder mutation (999del5), and sought to identify prognostic factors among the BRCA2 mutation-positive subset, including markers of genetic instability (aneuploidy) and mitotic activity (S-phase fraction). We established the genetic status of 2,967 Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers) diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the country during this period. Tumour ploidy and S-phase fraction were assessed on tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with respect to mutation status. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival by BRCA2 status, using Cox regression. After a median follow-up of 9.5 years, BRCA2 mutation carriers had a higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24-2.16, p < 0.001). The risk increase was restricted to women with diploid tumours (HR 3.03, 95 % CI 1.91-4.79, p < 0.001). Among breast cancer patients with aneuploid tumours, survival of carriers was similar to that of noncarriers (HR 0.76, 95 % CI 0.41-1.41, p = 0.38). Increased tumour size and a positive nodal status predicted worse prognosis in all patients, whereas the highly correlated prognostic factors diploidy, low proliferative activity and a positive estrogen receptor status had reverse effects in mutation carriers and noncarriers. Breast cancer patients who carry the Icelandic founder BRCA2 mutation have inferior long-term survival than noncarriers, but the adverse prognosis is restricted to mutation carriers with diploid, slowly proliferating tumours.

Objective: To investigate whether employment status and work experiences, assessed in terms of job resources (organizational culture and superiors' and co-workers' support), commitment to organization, work motives, and experiences of discrimination, differ between survivors of prostate or testicular cancer or lymphoma and cancer-free reference subjects., Methods: Questionnaires were sent to 1349 male cancer survivors and 2666 referents in Denmark, Finland, Iceland, and Norway. Valid responses were 59% and 45%, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression models., Results: Compared to the referents, survivors of lymphoma and prostate cancer were less likely to be employed (OR=0.53; CI: 0.30-0.95 and OR=0.50; CI: 0.35-0.73, respectively), but decreased employment was not evident among testicular cancer survivors. Testicular cancer survivors experienced less discrimination at work than did the referents, for example, testicular cancer survivors were less likely to report that their colleagues doubted their ability to carry out their work tasks (OR=0.38; CI: 0.17-0.83). Lymphoma survivors were less likely than the referents to praise their workplace as an enjoyable place to work (OR=0.48; CI: 0.26-0.88). The prostate cancer survivors were more likely than the referents to find the organizational climate competitive, distrustful, and suspicious., Conclusions: Employment participation and work experiences of male cancer survivors varied substantially according to type of cancer. Occupational therapists and other health care personnel should keep this in mind when assisting cancer survivors in identifying their strengths and limitations at work.

Introduction: The nationwide Icelandic Cancer Registry (ICR) was established in 1954 and has been extensively used for research from the outset although formal quality assessment of the registry database has not previously been undertaken. In this paper we report the first formal evaluation of the comparability, validity, timeliness and completeness of the ICR., Material and Methods: Data from the ICR for the period 1955-2009 (41 994 cancer diagnoses) were used, applying established quantitative and semi-quantitative methods. In order to evaluate the completeness of the ICR, record linkage was performed between the ICR and the population-based Hospital Discharge Registry to identify potential missing cases for tumour diagnoses in 2000 and 2001., Results: The registration is in accordance with internationally accepted standards. It has high validity, but random variation in rates is prominent in this small population. Record linkage with the Hospital Discharge Registry revealed that in addition to the 2459 cancers registered in 2000-2001, 21 cases were missing, indicating 99.15% completeness. Tumours of the central nervous system constituted 71%, and haematological malignancies 19% of these missing entries., Discussion: The ICR has high completeness, validity and timeliness and is comparable to the cancer registries of the other Nordic Countries. As cancer registries have many important roles, it is of great importance that their data are at all times as complete and valid as possible. Thus the ICR aims to constantly improve and update the data gathering process.

Objective: Colon cancer is the second most common cause of cancer death in Iceland and accounts for 8% of malignancies. We related information on symptoms of colon cancer patients with information on tumor location and pTNM-stage., Material and Methods: The study is retrospective and population-based. Information on all patients diagnosed with colon cancer in Iceland in 1995-2004 was obtained. Information on symptoms of patients and blood hemoglobin was collected from patients' files. The pathological parameters were derived from a previously performed study., Results: A total of 768 patients (422 males, 346 females) participated in this study. Median age was 73 years. Nearly 60% had anemia at the time of diagnosis, 53% had visible blood in stools, and 65% had changes in bowel habits. Around 84% had visible blood in stools and/or anemia. Of those with right-sided tumors, 75% had anemia and were more likely to be diagnosed incidentally (40%) than those with left-sided tumors (20%). Left-sided tumors were associated with blood in stools (68% compared to 41%, p < 0.05) and changes in bowel habits (74% compared to 57%, p < 0.05). Multivariate analysis indicated that blood in stools was strongly associated with a lower TNM-stage (OR = 0.75, p < 0.05). Anemia was strongly associated with a higher TNM-stage (OR = 1.84, p < 0.05)., Conclusion: Right-sided tumors were associated with anemia and incidental diagnosis; left-sided tumors were associated with visible blood in stools and changes in bowel habits. Visible blood in stools was significantly associated with lower TNM-stage, whereas abdominal pain, general and acute symptoms were associated with higher TNM-stage.

Routinely used prognostic factors fail to predict clinical outcome in a significant proportion of breast cancer patients, implying that they can not detect some important biological characteristics. Chromosomal changes have been described in breast carcinomas for many years but their significance is not clear. We compared chromosomal changes with clinico-pathological characteristics and clinical outcome in 203 breast cancer patients with a follow-up of 9-18 years. Combining data from classical cytogenetics and flow cytometry revealed chromosomal abnormalities in 142 cases (70%). Of these, 51 (35.9%) contained two or more cytogenetically abnormal clones. Polyclonality was significantly associated with poor breast-cancer-specific survival (P = 0.03) within 5 years, independent of tumor size, lymph node metastases, and hormone receptors. Specific changes were similar to those previously described, but a new finding was a significant association between del 3p12p21 and poor survival. Polyclonality was significantly associated with TP53-mutations but not with a germline BRCA2 mutation. Less than one third of the polyclonal samples were identified by flow cytometry alone. Cytogenetic changes were detected in 17 out of 114 samples from non-tumorous tissue (15%), two of them identical with a clone in the corresponding tumor. Several samples contained clearly unrelated clones within the tumor and outside, implying either multifocal origin or early divergence. In conclusion, the common deletion on Chromosome 3p12p21 was associated with poor clinical outcome. Chromosomal polyclonality is common in breast carcinomas and predicts poor survival. Polyclonality was poorly detected by one-sample flow cytometry. Multiple sampling might improve the detection rate., (Copyright © 2011 Wiley-Liss, Inc.)

Earlier menarche correlates with shorter adult height and higher childhood body fat. We conducted a genome-wide association study of age at menarche (AAM) on 15,297 Icelandic women. Combined analysis with replication sets from Iceland, Denmark and the Netherlands (N = 10,040) yielded a significant association between rs314280[T] on 6q21, near the LIN28B gene, and AAM (effect = 1.2 months later per allele; P = 1.8 × 10(-14)). A second SNP within the same linkage disequilibrium (LD) block, rs314277, splits rs314280[T] into two haplotypes with different effects (0.9 months and 1.9 months per allele). These variants have been associated with greater adult height. The association with adult height did not account for the association with AAM or vice versa. Other variants, previously associated with height, did not associate significantly with AAM. Given the link between body fat and AAM, we also assessed 11 variants recently associated with higher body mass index (BMI) and 5 of those associated with earlier AAM.

Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.

Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.

Unlabelled: Earlier studies have shown that cancer risk is related to educational level in many countries. The relationship between education and cancer risk has not been studied in the small, but ethnically homogenous, Icelandic population postulated to be outstanding as regards social equity., Material and Methods: We conducted a follow-up study of a cohort of 60,194 males and 58,505 females aged 20-64 at census 1981 in Iceland. Information on education from the census was classified into three educational groups and linked with the population-based Icelandic Cancer Registry. Standardized incidence ratios (SIRs) were calculated for the period 1982 to 2004., Results: We found a significant association between educational level and cancer risk. Among males with academic education, the SIR was elevated for prostate cancer (SIR=1.17, 95% CI 1.05-1.30) and melanoma (SIR=1.41, 95% CI 1.00-1.93) and lowered for cancers of the lung (SIR=0.72, 95% CI 0.59-0.87) and stomach (SIR=0.67, 95% CI 0.48-0.90). Women with academic education had an increased risk of breast cancer (SIR=1.19, 95% CI 1.07-1.33) and a decreased risk of lung cancer (SIR=0.49, 95% CI 0.36-0.65). Increasing educational level was associated with a lowered risk of cervical cancer (p trend=0.017)., Discussion: The association between education and cancer incidence seen in this study resembles observations from other countries and probably reflects concordance between social status and certain risk factors for cancer. Our study confirms health-related socioeconomic differences in Iceland and must be taken into account when programmes for health promotion are planned.

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

Background: Bactericidal-permeability-increasing protein (BPI) is a potent anti-microbial protein produced by neutrophil granulocytes. Anti-neutrophil cytoplasmatic antibodies (ANCA) directed against BPI have been detected in up to 91% in patients with cystic fibrosis (CF). We aimed to evaluate the prevalence of BPI-ANCA in our CF patients and to determine whether presence of BPI-ANCA is correlated with organ damage., Methods: Twenty-four patients performed respiratory function testing and pulmonary high-resolution computed tomography (HRCT). HRCT was scored by using a modified Bhalla method. Serum samples were analysed by direct binding enzyme-linked immunosorbent assay for BPI-ANCA., Results: The prevalence of anti-BPI-IgG was 71% and anti-BPI-IgA 33%. Twenty-nine percent of our patients were positive for both BPI-ANCA isotypes. Mean HRCT score was 8.0 ranging from 0 to 22, bronchiectasis presented the most common finding (79%). There was a significant correlation between BPI-ANCA and both HRCT score and FEV(1) (p < 0.01). High levels of BPI-ANCA were correlated to chronic Pseudomonas aeruginosa lung infection (p < 0.01)., Conclusions: BPI-ANCA was common in our study group. Highly significant correlations between BPI-ANCA and parameters to evaluate lung disease in CF may be a consequence of the inflammation process, or it may indicate a pathogenic role of BPI-ANCA levels in the development of lung disease. More research is needed and the clinical significance of our findings needs further evaluation.

Background: Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear., Methods: In a case-control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis., Results: An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years., Conclusion: The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast.

The incidence of Crohn's disease (CD) and ulcerative colitis (UC) in children in western Norway was estimated in a prospective epidemiological study during the years 1984 and 1985. The total population in the area was 807,000 and the child population was 198,570 (1984). There were 27 new cases of chronic inflammatory bowel disease (IBD) in children aged 15 years or less, 10 new cases of CD, and 17 of UC. The mean annual incidence of CD in the child population was 2.5/100,000/year, whereas the incidence of UC in the child population was 4.3/100,000/year. Nearly all the children had abdominal symptoms. In this study, we found an incidence of CD in children that is the highest hitherto reported, to our knowledge. To the contrary, the incidence of UC was considerably lower than previously reported from northern Europe.