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Aalen O.O.,University of Oslo | Aalen O.O.,Institute of Population Based Cancer Research | Valberg M.,University of Oslo | Grotmol T.,Institute of Population Based Cancer Research | Tretli S.,Institute of Population Based Cancer Research
International Journal of Epidemiology | Year: 2015

The concept of frailty plays amajor role in the statistical field of survival analysis. Frailty variation refers to differences in risk between individuals which go beyond known or measured risk factors. In other words, frailty variation is unobserved heterogeneity. Although understanding frailty is of interest in its own right, the literature on survival analysis has demonstrated that existence of frailty variation can lead to surprising artefacts in statistical estimation that are important to examine. We present literature that demonstrates the presence and significance of frailty variation between individuals. We discuss the practical content of frailty variation, and show the link between frailty and biological concepts like (epi)genetics and heterogeneity in disease risk. There are numerous suggestions in the literature that a good deal of this variation may be due to randomness, in addition to genetic and/or environmental factors. Heterogeneity often manifests itself as clustering of cases in families more than would be expected by chance. We emphasize that apparently moderate familial relative risks can only be explained by strong underlying variation in disease risk between families and individuals. Finally, we highlight the potential impact of frailty variation in the interpretation of standard epidemiological measures such as hazard and incidence rates. © The Author 2014.


Brustugun O.T.,University of Oslo | Moller B.,Institute of Population Based Cancer Research | Helland A.,University of Oslo
British Journal of Cancer | Year: 2014

Background: The severity of cancers is often measured in number of deaths. However, number of years of life lost (YLL) may be a more appropriate indicator of impact on society. Here we have calculated the YLL of adult cancers in Norway for the year 2012, as well as for the previous 15-year period. Methods: Data on age composition, expected remaining years of life, total numbers of deaths and deaths due to cancer were retrieved from the National Census Agency Statistics Norway. YLL were calculated for both sexes aged 25-99 years based on each individual's age at death, and the expected remaining years of life at that age. Results: Cancer deaths represented 25.8% of all adult deaths in 2012, with a lower fraction of females (28.7% in men and 23.1% in women), whereas cancer represented 35.2% of all YLL, with a higher fraction of females (32.8% in men and 37.8% in women). Females loose on average more life years to cancer than men (14.9 vs 12.7 years). Average YLL varied from 23.7 (cervical cancer) to 7.9 (prostate cancer). Lung cancer caused almost as many YLL alone (22.1% of cancer-caused YLL) as colon, prostate and breast cancer combined (23.1%). From 1997 to 2012, cancer-caused YLL as a fraction of all YLL increased from 32.5% to 35.2%, but with major differences among diagnoses. Conclusions: Cancer is a major and increasing cause of premature deaths, and YLL may be a more accurate measure than number of deaths. Public health efforts and research funding should be explicitly directed at preventing premature deaths. © 2014 Cancer Research UK.


Larsen I.K.,Institute of Population based Cancer Research | Bray F.,Institute of Population based Cancer Research | Bray F.,University of Oslo
International Journal of Cancer | Year: 2010

There have been rapid increases in the incidence of colorectal cancer in Norway since the 1960s, and rates rank among the highest worldwide. The primary objectives are to describe trends in left- and right-sided colon cancer and rectal cancer by calendar period and birth cohort and to generate hypotheses as to the etiological factors in operation. Although the ageadjusted incidence rates of both colon and rectal cancer increased in Norway in both sexes up to the 1980s, subsite- and age-specific analyses reveal a deceleration in the rate of increase thereafter, apparent in the rates of both left-sided colon and rectal cancer. Overall trends in incidence of right-sided colon cancer continue to increase in both sexes. Rates in both left- and right-sided colon cancers have tended to stabilize or decrease among successive generations born after 1950, however, while incidence rates of rectal cancer appear to be increasing in recent generations. The all-ages rates are thus in keeping with the commonly reported "left to right shift" of colon cancer, although standardization masks important observations. The cohort patterns provide further evidence that factors earlier in life are important, and while the complex etiology makes interpretation difficult, modifications in diet, obesity and physical activity in Norway are likely among the drivers of the trends in one or more of the colorectal subsites examined. In summary, the recent downturn in the disease at younger ages provides some reason for optimism, although possible increases in rectal cancer among recent birth cohorts are of concern. © 2009 UICC.


Tretli S.,Institute of Population based Cancer Research | Tretli S.,Norwegian University of Science and Technology | Schwartz G.G.,Wake forest University | Torjesen P.A.,University of Oslo | Robsahm T.E.,Institute of Population based Cancer Research
Cancer Causes and Control | Year: 2012

Purpose: We investigated the association between serum levels of 25-hydroxyvitamin D (25-OHD) and risk of death in Norwegian cancer patients. Methods: The study population was 658 patients with cancers of the breast (n = 251), colon (n = 52), lung (n = 210), and lymphoma (n = 145), obtained from JANUS, a population-based serum bank in Norway. Serum samples were collected within 90 days of cancer diagnosis and were analyzed for 25-OHD. Patients were diagnosed during 1984-2004 and were followed for death throughout 2008. We used Cox regression models to assess the relationship between serum 25-OHD and risk of death. Results: Three hundred and ninety-nine patients died during follow-up, of whom 343 (86%) died from cancer. Adjusted for sex, age at diagnosis, and season of blood sampling, patients with 25-OHD levels below 46 nmol/L at diagnosis experienced shorter survival. Compared to patients in the lowest quartile of serum 25-OHD, the risk of cancer death among patients in the highest quartile was significantly reduced (HR 0.36 95% CI 0.27, 0.51). The estimated change in risk of cancer death was most pronounced between the first and the second quartile. The associations between 25-OHD levels and survival were observed for all four cancers. Conclusions: Higher circulating serum levels of 25-OHD were positively associated with the survival for cancers of the breast, colon, lung, and lymphoma. © 2011 The Author(s).


Skaane P.,University of Oslo | Bandos A.I.,University of Pittsburgh | Eben E.B.,University of Oslo | Jebsen I.N.,University of Oslo | And 6 more authors.
Radiology | Year: 2014

Purpose: To compare the performance of two versions of reconstructed two-dimensional (2D) images in combination with digital breast tomosynthesis (DBT) versus the performance of standard full-field digital mammography (FFDM) plus DBT. Materials and Methods: This trial had ethical committee approval, and all participants gave written informed consent. Examinations (n = 24 901) in women between the ages of 50 and 69 years (mean age, 59.2 years) were interpreted prospectively as part of a screening trial that included independent interpretations of FFDM plus DBT and reconstructed 2D images plus DBT. Reconstructed 2D images do not require radiation exposure. Using analyses for binary data that accounted for correlated interpretations and were adjusted for reader-specific volume, two versions (initial and current) of reconstructed 2D images used during trial periods 1 (from November 22, 2010, to December 21, 2011; 12 631 women) and 2 (from January 20, 2012, to December 19, 2012; 12 270 women) were compared in terms of cancer detection and false-positive rates with the corresponding FFDM plus DBT interpretations. Results: Cancer detection rates were 8.0, 7.4, 7.8, and 7.7 per 1000 screening examinations for FFDM plus DBT in period 1, initial reconstructed 2D images plus DBT in period 1, FFDM plus DBT in period 2, and current reconstructed 2D images plus DBT in period 2, respectively. False-positive scores were 5.3%, 4.6%, 4.6%, and 4.5%, respectively. Corresponding reader-adjusted paired comparisons of false-positive scores revealed significant differences for period 1 (P =.012) but not for period 2 (ratio = 0.99; 95% confidence interval: 0.88, 1.11; P =.85). Conclusion: The combination of current reconstructed 2D images and DBT performed comparably to FFDM plus DBT and is adequate for routine clinical use when interpreting screening mammograms. © 2014 RSNA.


Stensheim H.,Institute of Population based Cancer Research | Cvancarova M.,Institute of Population based Cancer Research | Cvancarova M.,University of Oslo | Moller B.,Institute of Population based Cancer Research | Fossa S.D.,University of Oslo
International Journal of Cancer | Year: 2011

Despite fertility-preserving initiatives, postcancer reproduction is expected to be lower than that of the general population. Using data from the Cancer Registry and the Medical Birth Registry of Norway, postcancer pregnancy rates were analyzed in 27,556 survivors and compared to those from a matched comparison group ("controls") from the general population. All were born after 1950, diagnosed from 1967 to 2004 at age of 16-45, and had an observation time from the date of diagnosis (assigned date for controls), until pregnancy, death, age 46, or December 31, 2006. Cox regression was used to estimate pregnancy rates, after adjusting for educational level, parity and diagnostic period. Overall, cancer survivors had a lower pregnancy rate than the controls, but the rate for survivors was higher in males than in females [hazard rate (HR) = 0.74 (95% confidence interval (CI) 0.71-0.78) and HR = 0.61 (95% CI 0.58-0.64), respectively]. However, the rates did not differ between controls and survivors of malignant melanoma or thyroid cancer. By contrast, the lowest HRs for pregnancy occurred in survivors of leukemia, cervical or breast cancer. Increased pregnancy rates during the study period were detected for ovarian cancer [HR = 0.2 (95% CI 0.1-0.3) to HR = 0.7 (95% CI 0.5-0.9)], testicular cancer [HR = 0.6 (95% CI 0.4-0.9) to HR = 0.8 (95% CI 0.7-0.8)], and Hodgkin lymphoma diagnosed in men [HR = 0.7 (95% CI 0.5-0.9) to HR = 0.9 (95% CI 0.7-1.0)]. In summary, fertility-preserving attempts have succeeded in patients with ovarian or testicular cancer and in males with Hodgkin lymphoma. Male survivors initiated pregnancies in a higher degree than female survivors. Copyright © 2011 UICC.


Gislefoss R.E.,Institute of Population based Cancer Research | Grimsrud T.K.,Institute of Population based Cancer Research | Morkrid L.,University of Oslo
Clinical Biochemistry | Year: 2015

The potential value of a biobank depends on the quality of the samples, i.e. how well they reflect the biological or biochemical state of the donors at the time of sampling. Documentation of sample quality has become a particularly important issue for researchers and users of biobank studies. Objective: The aim of this study was to investigate the long-term stability of selected components: cholesterol, high density cholesterol (HDLC), low density cholesterol (LDLC), apolipoprotein A1 (apo-A1), apolipoprotein B (apo B), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH) and free thyroxin (FT4). Design and methods: Samples, stored at - 25. °C, from 520 men aged 40-49. years at blood sampling distributed in equally sized groups (n= 130) according to length of storage, 0, 4, 17 and 29. years, respectively, were used in a cross sectional design. The freshly collected serum samples were used as a reference group to calculate storage related changes. Results: The differences between fresh samples and samples stored for 29. years were substantial for apo-A1 (+. 12%), apo-B (+. 22.3%), HDLC (- 69.2%), LDLC (+. 31.3%), and PRL (- 33.5%), while total cholesterol, FSH, LH, TSH and FT4 did not show any significant difference. Conclusions: The study showed large differences in serum level of the selected components. The lipids and apolipoproteins were all changed except for total cholesterol. Most hormones investigated (FSH, LH, TSH and FT4) proved to be stable after 29. years of storage while PRL showed sign of degradation. The observed differences are probably due to long-term storage effects and/or external factors (i.e. diet and smoking). © 2014 The Canadian Society of Clinical Chemists.


Sagerup C.M.T.,University of Oslo | Smastuen M.,Institute of Population Based Cancer Research | Johannesen T.B.,Institute of Population Based Cancer Research | Helland A.,University of Oslo | Brustugun O.T.,University of Oslo
Thorax | Year: 2011

Background and aim: Lung cancer is increasingly affecting women. The aim of this study was to identify sex-specific trends in lung cancer incidence and survival. Methods: Complete national data on 40 118 cases from the Cancer Registry of Norway sampled from 1988 to 2007 are presented, with incidence rates, 1- and 5-year relative survival in 5 year intervals and multivariate HRs adjusted for covariates, each with 95% CIs. Results: Lung cancer incidence increased by 64%, with an age-adjusted annual average increase of 4.9% in women and 1.4% in men in this period. Relative survival was lower in men than in women in all time periods, and men had an increased risk of dying within 5 years of diagnosis compared with women (HR 1.14, 95% CI 1.11 to 1.17), adjusted for covariates. Adenocarcinoma is now the most frequent histological group in men and women, yet the risk of dying was higher in men in all histological subtypes except squamous cell carcinoma. A higher proportion of women than men were diagnosed with localised disease, and the risk of dying was significantly higher in men among all stages, most apparent in localised disease (HR 1.25, 95% CI 1.18 to 1.33). Conclusion: The findings highlight important characteristics of the lung cancer epidemic; despite a rising incidence of female lung cancer cases, women are diagnosed with less advanced disease than men; when adjusted for covariates, men have an increased risk of excess death at 5 years compared with women, irrespective of stage, age, period of diagnosis and selected histological subgroups.


Zienolddiny S.,National Institute of Occupational Health | Haugen A.,National Institute of Occupational Health | Lie J.-A.S.,National Institute of Occupational Health | Kjuus H.,National Institute of Occupational Health | And 2 more authors.
Breast Cancer Research | Year: 2013

Introduction: Some studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. We aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk.Methods: We conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. We studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. The statistically significant odds ratios were tested for noteworthiness using two Bayesian tests: false positive report probability (FPRP) and Bayesian false discovery probability (BFDP).Results: In the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2 (rs17024926), ROR-b (rs3903529, rs3750420), MTNR1A (rs131113549) and PER3 (rs1012477).Conclusions: Significant and noteworthy associations between several polymorphisms in circadian genes, night work and breast cancer risk were found among nurses who had worked at least three consecutive night shifts. © 2013 Zienolddiny et al.; licensee BioMed Central Ltd.


Grimsrud T.K.,Institute of Population based Cancer Research | Andersen A.,Institute of Population based Cancer Research
Journal of Occupational Medicine and Toxicology | Year: 2010

Background: Increased risks of nasal cancer and lung cancer in nickel refiners have been investigated scientifically and discussed since they were detected in the 1930s. Nickel compounds are considered to be the main cause of the cancer excess. Parts of the nickel producing industry and their consultants oppose the classification of water-soluble nickel salts as human carcinogens, and argue that the risk in exposed workers should be ascribed to other occupational exposures and smoking. Discussion. Respiratory cancer risks in Welsh, Finnish, and Norwegian nickel refiners add to the evidence of carcinogenicity of water-soluble nickel. In Norwegian refiners, the first epidemiological study in 1973 identified high risks of lung cancer and nasal cancer among long-term electrolysis workers. Risk analyses based on exposure estimates developed in the 1980s supported the view that water-soluble nickel compounds were central in the development of cancer. Recently, new exposure estimates were worked out for the same cohort based on personal monitoring of total nickel and chemical determination of four forms of nickel. Additional data have been collected on life-time smoking habits, and on exposure to arsenic, asbestos, sulphuric acid mists, cobalt, and occupational lung carcinogens outside the refinery. After adjustment for these potential confounding exposures in case-control analyses, the risk pattern added to the evidence of an important role of water-soluble nickel compounds as causes of lung cancer. These Norwegian cancer studies rely on national Cancer Registry data, considered close to complete from 1953 onwards; and on National Population Register data continuously updated with mortality and emigration. Canadian mortality studies - perceived to offer the strongest support to the industry position not to recognise carcinogenicity of water-soluble nickel - appear to suffer from limitations in follow-up time, loss to follow-up, absence of risk analysis with individual exposure estimates, no confounder control, and a likely underestimation of cancer mortality. Conclusions: Rejection to recognise water-soluble nickel as a human carcinogen seems to contradict material epidemiological evidence that demonstrates a strong association between water-soluble nickel compounds and risks of lung cancer and nasal cancer. Independent international scientific bodies have classified nickel compounds as carcinogenic to humans, inclusive of water-soluble nickel. © 2010 Grimsrud and Andersen; licensee BioMed Central Ltd.

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