Institute of Cancer Epidemiology

Copenhagen, Denmark

Institute of Cancer Epidemiology

Copenhagen, Denmark

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Benveniste H.,Health Level | Zhang S.,State University of New York at Stony Brook | Reinsel R.A.,Health Level | Li H.,State University of New York at Stony Brook | And 6 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2012

Cancer patients without evidence of brain metastases often exhibit constitutional symptoms, cognitive dysfunction and mood changes at the time of clinical diagnosis, i.e. prior to surgical and/or chemotherapy treatment. At present however, there is limited information on brain metabolic and functional status in patients with systemic cancers such as lung cancer prior to initiation of treatment. Therefore, a prospective, observational study was conducted on patients with a clinical diagnosis of lung cancer to assess the cerebral metabolic status before treatment using proton magnetic resonance spectroscopy ( 1HMRS). Together with neurocognitive testing, 1HMRS was performed in the parietal and occipital cortices of patients diagnosed with a lung mass (N=17) and an age-matched control group (N=15). Glutamate concentrations in the occipital cortex were found to be lower in the patients compared to controls and the concentrations of creatine and phosphocreatine were significantly lower in the parietal cortex of the patients. The lung cancer patients were also characterized by greater fatigue scores (but not depression) prior to treatment when compared to controls. In addition, the serum concentration of interleukin-6 (proinflammatory cytokine) was higher in patients compared to controls; and the concentration of tumor-necrosis factor alpha ([TNF-α]) was positively correlated to the metabolic activity of the lung tumor as defined by the 2-deoxy-2-( 18F)fluoro-D-glucose ( 18FDG) positron emission tomography (PET) derived maximal standardized uptake values (SUV max). Finally, multivariate statistical modeling revealed that the concentration of N-acetyl-aspartate [NAA] in the occipital cortex was negatively associated with [TNF-α]. In conclusion, our data demonstrate that the cerebral metabolic status of patients with lung cancer is changed even prior to treatment. In addition, the association between inflammatory cytokines, SUVmax and [NAA] points towards interactions between the cancer's inherent metabolic activity, systemic subclinical inflammation and brain function.


Wermuth L.,University of Southern Denmark | Lassen C.F.,Institute of Cancer Epidemiology | Himmerslev L.,Institute of Cancer Epidemiology | Olsen J.,Institute of Cancer Epidemiology | Ritz B.,University of California at Los Angeles
Danish Medical Journal | Year: 2012

INTRODUCTION: Denmark has a long-standing tradition of maintaining one of the world's largest health science specialized register data bases as the National Hospital Register (NHR). To estimate the prevalence and incidence of diseases, the correctness of the diagnoses recorded is critical. Parkinson's disease (PD) is a neurodegenerative disorder and only 75-80% of patients with parkinsonism will have idiopathic PD (iPD). It is necessary to follow patients in order to determine if some of them will develop other neurodegenerative diseases and a one-time-only diagnostic code for iPD reported in the register may be incorrect. MATERIAL AND METHODS: This was a large nationwide popu lation-based study of risk factors for iPD, called Parkinson's disease in Denmark (PASIDA). We evaluated the iPD diagnosis reported in the NHR. Medical records with primary diagnoses of iPD from six neurological departments were collected and abstracted using a standardized system to review the diagnostic accuracy of the ICD codes. RESULTS: Among the 1,040 medical records abstracted, 857 (82.4%) patients met our criteria for iPD. 183(17.6%) of the patients suffered from other diagnoses such as atypical PD (66 patients), secondary PD (60 patients) and other diagnoses (46 patients). CONCLUSION: Possibly only about 82% of the patients with the primary diagnosis of iPD in the Danish NHR actually suffered from iPD. To improve diagnostic validity, we appeal to update the ICD code and to identify the correct parkinsonian phenotype to reduce biased case sampling in register- based studies and appropriate treatment for these rare diseases. FUNDING: This study was supported by a grant from the National Institutes of Environmental Health Sciences, USA (grant No R01 ES013717). The funding source had no role in the design or analysis of the study or in the decision to submit the manuscript for publication.


Baandrup L.,Institute of Cancer Epidemiology | Munk C.,Institute of Cancer Epidemiology | Andersen K.K.,Danish Cancer Society | Junge J.,Copenhagen University | And 3 more authors.
Gynecologic Oncology | Year: 2012

Objective: To evaluate if women with HPV16 positive CIN2 and CIN3 are diagnosed at a younger age. Methods: We conducted a population-based cohort study including more than 40,000 women having a liquid based cervical cytology sample taken as part of routine screening. HPV analysis was performed using Hybrid Capture 2 and LiPAv2. The study population was linked to the Danish Pathology Data Bank to retrieve information on subsequent cervical histology. We included HR HPV positive CIN2/3 samples, comprising 173 CIN2 and 467 CIN3 lesions. Due to a high number of multiple concurrent HPV infections, the causative HPV type was assigned to a hierarchically group. Results: In CIN3, the estimated proportion of lesions positive for HPV16 was 68.1% among women aged 20 years and decreased to 38.9% among women aged 50 years. A decrease in HPV16 positivity with increasing age was also observed in CIN2. In a multinomial logistic regression analysis, young age was strongly associated with HPV16 positivity in CIN3 lesions (OR = 0.46 per 10 year increase in age, 95% CI: 0.32-0.65). The proportion of HPV16 and/or 18 positive lesions among women diagnosed with CIN2 and CIN3 below 30 years of age was 44% and 75%, respectively. Conclusions: HPV16 positivity was significantly associated with younger age at diagnosis of CIN3. In a population vaccinated against HPV16 and 18, we will experience a shift to older ages in cervical precancerous lesions. These findings may imply that cervical cancer screening programs could start at an older age in HPV vaccinated populations. © 2011 Elsevier Inc. All rights reserved.


Hannibal C.G.,Institute of Cancer Epidemiology | Huusom L.D.,Institute of Cancer Epidemiology | Kjaerbye-Thygesen A.,Institute of Cancer Epidemiology | Tabor A.,Copenhagen University | And 3 more authors.
Acta Obstetricia et Gynecologica Scandinavica | Year: 2011

Objective. To examine period-, age- and histology-specific trends in the incidence rate of borderline ovarian tumors in Denmark in 1978-2006. Design. Register-based cohort study. Setting. Denmark 1978-2006. Population. 5 079 women diagnosed with a borderline ovarian tumor in at least one of two nationwide registries (4 312 epithelial tumors and 767 non-epithelial/unspecified tumors). Methods. Estimation of overall incidence rates and period-, age- and histology-specific incidence rates. Age-adjustment was done using the World Standard Population. To evaluate incidence trends over time, we estimated average annual percentage change and 95% confidence intervals (CI) using log-linear Poisson models. Main Outcome Measures. Age-standardized and age-specific incidence rates and average annual percentage change. Results. The incidence of epithelial borderline ovarian tumors increased from 2.6 to 5.5 per 100 000 women-years between 1978 and 2006, with an average annual percentage change of 2.6% (95% CI: 2.2-3.0). The median age at diagnosis was 52 years. Women 40 years or older had a higher average annual percentage change than women younger than 40 years. Most tumors were mucinous (49.9%) and serous tumors (44.4%). Women with mucinous tumors were younger at diagnosis (50 years) compared with women with serous tumors (53 years). Women with serous tumors had a higher average annual percentage incidence change than women with mucinous tumors. Conclusions. The incidence rate of borderline ovarian tumors increased significantly in Denmark in 1978-2006. In line with results for ovarian cancer, Denmark had a higher incidence rate of borderline ovarian tumors compared with the other Nordic countries in 1978-2006. © 2011 The Authors.


Hvilsom G.B.,Danish Cancer Society | Hvilsom G.B.,Institute of Cancer Epidemiology | Holmich L.R.,Herlev University Hospital | Steding-Jessen M.,Danish Cancer Society | And 9 more authors.
Annals of Plastic Surgery | Year: 2012

We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during the period between 1999 and 2006. A history of radiation therapy was associated with increased risk of severe capsular contracture for 1- and 2-stage procedures, with adjusted hazard ratios (HR) of 3.3 (95% confidence interval [CI]: 0.9ĝ€"12.4) and 7.2 (95% CI: 2.4ĝ€"21.4), respectively. Similarly, a history of radiation therapy was associated with a non-significantly increased risk of reoperation after both 1-stage (HR ≤ 1.4; 95% CI: 0.7ĝ€"2.5) and 2-stage (HR ≤ 1.6; 95% CI: 0.9ĝ€"3.1) procedures. Reconstruction failure was highest (13.2%) in the 2-stage procedures with a history of radiation therapy. Breast reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy. Copyright © 2012 by Lippincott Williams & Wilkins.


Kharazmi E.,German Cancer Research Center | Hemminki K.,German Cancer Research Center | Hemminki K.,Lund University | Pukkala E.,University of Tampere | And 8 more authors.
European Urology | Year: 2015

Background None of the population-based epidemiologic studies to date has had a large enough sample size to show the familial risk of testicular cancer (TC) by age at diagnosis for patients and their relatives or for rare histologic subtypes. Objective To estimate absolute and relative risks of TC in relatives of TC patients by age at diagnosis in patients and their relatives and histological subtypes. Design, setting, and participants In a joint population-based cohort study, 97 402 first-degree relatives of 21 254 TC patients who were diagnosed between1955 and 2010 in five European countries were followed for cancer incidence. Outcome measurements and statistical analysis Standardized incidence ratios (SIRs) were estimated using histology-, age-, period-, and country-specific incidence rates as references. Lifetime cumulative risks were also calculated. Results and limitations The lifetime cumulative risk of TC in brothers of a patient with TC was 2.3%, which represents a fourfold increase in risk (SIR 4.1, 95% confidence interval [CI] 3.6-4.6) compared to the general population. TC in a father increased the risk by up to twofold in his son (95% CI 1.7-2.4; lifetime risk 1.2%) and vice versa. When there were two or more TC patients diagnosed in a family, the lifetime TC risk for relatives was 10-11%. Depending on age at diagnosis, twins had a 9-74% lifetime risk of TC. Family history of most of the histologic subtypes of TC increased the risk of concordant and most discordant subtypes. There was a tendency toward concordant age at diagnosis of TC among relatives. Conclusions This study provides clinically relevant age-specific cancer risk estimates for relatives of TC patients. Familial TC patients tended to develop TC at an age close to the age at diagnosis of TC among their relatives, which is a novel finding of this study. Patient summary This joint European population study showed that sons and brothers of testicular cancer patients are at higher risk of developing this cancer at an age close to the age at diagnosis of their relatives.


Fallah M.,German Cancer Research Center | Pukkala E.,Institute for Statistical and Epidemiological Cancer Research | Pukkala E.,University of Tampere | Sundquist K.,Lund University | And 5 more authors.
European Journal of Cancer | Year: 2014

Background We aimed to estimate lifetime cumulative risk of melanoma (CRM) in relatives of patients with melanoma by histology and age at diagnosis in patients and relatives. Methods A population-based cohort of 238 724 first-degree relatives of 46 091 melanoma patients diagnosed in 1955-2010 in Nordic countries was followed for cancer incidence. Findings The CRM (0-79 years) in first-degree relatives of a patient with superficial spreading (SSM), nodular (NM), or lentigo maligna melanoma was quite similar, ranging from 2.5% to about 3%, which represents about 2-fold increase over the general population risk. When one melanoma patient in the family was diagnosed before age 30, the CRM was about 3%. When there were ≥2 melanoma patients diagnosed before age 30 in a family, CRM for relatives was about 14%, 6% for diagnoses at age 30-59, and 5% for diagnoses at age 60 or older. Depending on age at diagnosis of same-sex twins (not known whether monozygotic/dizygotic), their CRM was about 7-21%. Although no familial case of concordant histological types of acral lentiginous/desmoplastic/compound nevus/spindle cell melanomas or malignant blue nevus was found, familial risks of discordant histological types of melanoma were interchangeably high for most of the types, e.g. higher risk of SSM when a first-degree relative had NM [standardized incidence ratios (SIR) = 2.6, 95% confidence interval (CI) = 2.1-3.3, n = 72] or acral lentiginous (4.0, 95%CI = 1.5-8.8, n = 6) and vice versa. There was a tendency toward concordant age at diagnosis of melanoma among relatives of melanoma patients. Interpretation Findings of this study may help clinicians to find subjects at high melanoma risk for the genetic counseling. The risk was highest when melanoma occurred in a same-sex twin, one first-degree relative diagnosed at young age (<30), or ≥2 first-degree relatives. Histological type of melanoma does not seem to play an important role in familial melanoma. Funding This work was supported by the Nordic Cancer Union, Swedish Council for Working Life and Social Research, and German Cancer Aid. © 2014 Elsevier Ltd. All rights reserved.


PubMed | Institute of Cancer Epidemiology, University of Tampere, Stanford University, University of Iceland and 2 more.
Type: Comparative Study | Journal: European urology | Year: 2015

None of the population-based epidemiologic studies to date has had a large enough sample size to show the familial risk of testicular cancer (TC) by age at diagnosis for patients and their relatives or for rare histologic subtypes.To estimate absolute and relative risks of TC in relatives of TC patients by age at diagnosis in patients and their relatives and histological subtypes.In a joint population-based cohort study, 97 402 first-degree relatives of 21 254 TC patients who were diagnosed between 1955 and 2010 in five European countries were followed for cancer incidence.Standardized incidence ratios (SIRs) were estimated using histology-, age-, period-, and country-specific incidence rates as references. Lifetime cumulative risks were also calculated.The lifetime cumulative risk of TC in brothers of a patient with TC was 2.3%, which represents a fourfold increase in risk (SIR 4.1, 95% confidence interval [CI] 3.6-4.6) compared to the general population. TC in a father increased the risk by up to twofold in his son (95% CI 1.7-2.4; lifetime risk 1.2%) and vice versa. When there were two or more TC patients diagnosed in a family, the lifetime TC risk for relatives was 10-11%. Depending on age at diagnosis, twins had a 9-74% lifetime risk of TC. Family history of most of the histologic subtypes of TC increased the risk of concordant and most discordant subtypes. There was a tendency toward concordant age at diagnosis of TC among relatives.This study provides clinically relevant age-specific cancer risk estimates for relatives of TC patients. Familial TC patients tended to develop TC at an age close to the age at diagnosis of TC among their relatives, which is a novel finding of this study.This joint European population study showed that sons and brothers of testicular cancer patients are at higher risk of developing this cancer at an age close to the age at diagnosis of their relatives.


Hansen H.P.,University of Southern Denmark | Tjornhoj-Thomsen T.,Copenhagen University | Johansen C.,University of Southern Denmark | Johansen C.,Institute of Cancer Epidemiology
Acta Oncologica | Year: 2011

Background. Today more and more people survive cancer. Cancer survivors need help to recover both from the cancer and the treatment. Rehabilitative interventions have been set up to meet their needs. However, there are studies that report no major effects following careful, targeted intervention. Furthermore, it seems difficult to define whether an effect is caused by the intervention or whether it is due to contextual parameters such as human interactions, the organisation, the staff, the physical surroundings or the general atmosphere. The present study examines the influence of three contextual parameters in rehabilitation courses for cancer survivors in Denmark. Methods. The study was based on an ethnographic fieldwork with participant observation at nine week-long courses, on in-depth interviews and on written sources. Fieldwork is well-suited for studying interventions in context, such as social interactions between people and their physical, material and institutional surroundings. The analysis is based on Duranti's and Goodwin's theoretical approach to context. Results. The findings are categorised into three contextual parameters. The setting, including its aesthetic value, its physical surroundings and the scheduling of the courses. The behavioural environment, which comprised work commitment and the care provided by the staff. The language environment insofar as it facilitated a sense of community. Discussion. The results demonstrate the influence of contextual parameters not formalised in the intervention programme. Contexts affect the outcome of an intervention because they frame and inform the teaching, communication and various forms of social gathering. The study suggests that the effects of the intervention as measured by quantitative studies cannot be properly interpreted without taking into account the context within which the intervention is embedded. © 2011 Informa Healthcare.


Hvilsom G.B.,Institute of Cancer Epidemiology
Plastic Surgical Nursing | Year: 2010

BACKGROUND: Prospective long-term data on the occurrence of complications following breast augmentation are sparse and the reported frequencies differ substantially. METHODS: The Danish Registry for Plastic Surgery of the Breast has prospectively registered preoperative, perioperative, and postoperative data for women undergoing breast augmentation in Denmark since 1999. From the Registry, the authors identified 5373 women with a primary cosmetic breast augmentation between 1999 and 2007. The authors calculated incidence proportions of adverse clinical outcomes within three time intervals (0 to 30 days, 0 to 3 years, and 0 to 5 years) after primary implantation. Outcomes of primary interest were capsular contracture, asymmetry/ displacement of the implant, hematoma, and infection. RESULTS: During the entire follow-up period (mean, 3.8 years; range, 0.1 to 8.7 years), 16.7 percent of the women were registered with an adverse event and 4.8 percent of the women were registered with a surgery-requiring complication. The most common adverse events within 30 days were hematoma (1.1 percent) and infections (1.2 percent), whereas the most common adverse events within 5 years were change of tactile sense (8.7 percent) and asymmetry/ displacement of implant (5.2 percent). Within 5 years, 1.7 percent of the women had a record of severe capsular contracture. Displacement/asymmetry and capsular contracture were the most frequent indications for reoperation with removal or exchange of the implant. CONCLUSIONS: Population-based complication frequencies among women with cosmetic breast augmentation in a Danish nationwide implant registry were generally lower than those reported in other studies, although frequencies of complications increased with length of follow-up. Copyright © 2009 by the American Society of Plastic Surgeons.

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