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Background: In utero exposure to maternal cancer and cancer treatment might influence the child's cognitive development. This study investigated if exposure to maternal cancer during fetal life impacted school performance and educational achievement as adults., Methods: This nationwide retrospective cohort study identified all live-born children in Denmark between January 1978 and December 2013. Exposure was defined as maternal cancer diagnosis during pregnancy. Four partly overlapping birth cohorts were constructed depending on the outcome of interest: (1) receiving special educational support for birth years 2001-2013; (2) grade point average (GPA) at the final exams after 10th grade for 1986-2003; (3) educational achievement at 20 years for 1978-1998; and (4) education at 30 years for 1978-1988. Logistic and linear models were adjusted for birth year, maternal age, maternal education and maternal death., Results: The estimated probability of receiving special educational support was similar in the exposed group and the reference (adjusted OR 0.96; 95% CI 0.46 to 1.77, non-significant). The GPA did not statistically differ (0.13 grade points; 95% CI -0.18 to 0.45, non-significant). The achieved educational levels were similar for the exposed group and the reference at 20 years, with an adjusted OR of 1.07 (95% CI 0.82 to 1.40) for low versus medium educational level, and at 30 years with an adjusted OR of 0.73 (95% CI 0.35 to 1.50) for low versus high educational level and of 1.07 (95% CI 0.66 to 1.72) for medium versus high educational level., Conclusion: Our findings did not indicate poorer performance in compulsory school nor impairment of adult educational achievement after exposure to maternal cancer in utero., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We aimed to investigate the risk of first primary cancer in patients with RA treated with janus kinase inhibitors (JAKi) compared with those who received biologic DMARDs (bDMARDs) in a real-world setting., Methods: We performed an observational cohort study using the nationwide registers in Denmark. Patients with RA aged 18+ years, without a previous cancer diagnosis, and who initiated treatment with JAKi or bDMARDs from 1 January 2017 to 31 December 2020 were followed for any cancer (except non-melanoma skin cancer). We applied inverse probability of treatment weighting (IPTW) to account for covariate differences between treatment groups. IPTW-generated weights were used with cause-specific Cox (CSC) models to calculate hazard ratios (HRs) for cancer incidence in JAKi-treated compared with bDMARD-treated patients with RA., Results: We identified 875 and 4247 RA patients treated with JAKi and bDMARDs, respectively. The JAKi group contributed 1315 person years (PYRS) and 19 cancers, the bDMARD group contributed 8597 PYRS and 111 cancers, with corresponding crude incidence rates per 1000 PYRS of 14.4 and 12.9. Comparing the two groups using weighted CSC models, a HR of 1.41 (95% CI 0.76, 2.37, 95% CIs) was seen for JAKi- vs bDMARD-treated patients with RA., Conclusion: JAKi treatment in real-world patients with RA was not associated with a statistically significant increased risk of first primary cancer compared with those who received bDMARDs. However, several numerically increased risk estimates were detected, and a clinically important excess risk of cancer among JAKi recipients cannot be dismissed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer., Methods: This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI)., Results: In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m 2 ) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m 2 ) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09-0.47)., Conclusions: Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population., (© 2023. The Author(s).)

Background: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation., Objective: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DII r ), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines., Methods: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders., Results: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DII r were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index., Conclusions: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements., Competing Interests: Conflicts of Interest Dr. James R. Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company that has licensed the right to his invention of the dietary inflammatory index (DII®) from the University of South Carolina in order to develop computer and smartphone applications for patient counseling and dietary intervention in clinical settings. Dr. Nitin Shivappa is an employee of CHI. The subject matter of this paper will not have any direct bearing on that work, nor has CHI-related activity exerted any influence on this project., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition., Methods: Concentrations of C-peptide-a marker for insulin secretion-were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C-peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI < 25 kg/m 2 , or WC < 80 cm, or WHR < 0.8) and overweight or obese (OW/OB; BMI ≥ 25 kg/m 2 , or WC ≥ 80 cm, or WHR ≥ 0.8) status for each of the three anthropometric measures separately: (1) MHNW, (2) MHOW/OB, (3) MUNW, and (4) MUOW/OB. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14-2.19) and WC (OR = 1.51, 95% CI = 1.09-2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94-1.77) definition. Conversely, women with the MHOW/OB and MUNW were not at statistically significant elevated risk of postmenopausal breast cancer risk compared to MHNW women., Conclusion: These findings suggest that being overweight or obese and metabolically unhealthy raises risk of postmenopausal breast cancer while overweight or obese women with normal insulin levels are not at higher risk. Additional research should consider the combined utility of anthropometric measures with metabolic parameters in predicting breast cancer risk., (© 2023 World Health Organization; licensed by John Wiley & Sons Ltd. Cancer Medicine published by Wiley Periodicals LLC.)

Purpose: In utero exposure to maternal cancer and cancer treatment might influence the child's short- and long-term health and development. The objective of the study was to investigate short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero., Methods: This nationwide cohort study identified all liveborn children in Denmark between January 1978 and December 2018. Exposure was defined as maternal cancer diagnosis during pregnancy, and in a subgroup analysis, exposure to chemotherapy in utero. The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Follow-up started at birth and ended at an event, death, emigration, or end of 2018. Hazard ratios of end points adjusted for potential confounders were estimated using Cox regression analysis., Results: Of 2,526,163 included liveborn children, 690 (0.03%) were exposed to maternal cancer in utero. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality, adjusted hazard ratio 0.8 (95% CI, 0.4 to 1.5), nor increased risk of congenital malformations, overall somatic or psychiatric disease. During the period 2002-2018, of 378 (0.03%) children exposed to cancer in utero, 42 (12.5%) were exposed to chemotherapy. Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases nor to congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy., Conclusion: Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.

Objectives: To investigate the obstetrical management of cancer in pregnancy and to determine adverse pregnancy and neonatal outcomes., Design: A nationwide cohort study., Setting and Population: We included all pregnancies (n = 4 071 848) in Denmark from 1 January 1973 to 31 December 2018., Methods: Exposure was defined as pregnancies exposed to maternal cancer (n = 1068). The control group comprised pregnancies without cancer. The groups were compared using logistic regression analysis and adjusted for potential confounders., Main Outcome Measures: The outcomes were induced abortion, preterm birth and adverse neonatal outcomes., Results: More women with cancer in pregnancy, as compared with the control group, experienced induced abortion (24.8% vs. 20.0%); first-trimester induced abortion adjusted odds ratio (aOR) 3.5 (95% confidence interval [CI] 2.7-4.5), second-trimester induced abortion; aOR 8.8 (95% CI 6.3-12.3), planned preterm birth (11.8% vs. 1.3%); aOR 10.8 (95% CI 8.0-14.6) and planned preterm birth at <32 gestational weeks; aOR 16.3 (95% CI 8.3-31.7). Neonates born to mothers with cancer in pregnancy had a higher risk of respiratory distress syndrome; aOR 3.5 (95% CI 2.8-4.4), low birthweight; aOR 3.8 (95% CI 3.1-4.8), admission to neonatal intensive care unit for >7 days; aOR 5.1 (95% CI 3.9-6.6), neonatal infection; aOR 1.8 (95% CI1.1-3.1) and neonatal mortality; aOR 4.7 (95% CI 2.7-8.2), but not of SGA; aOR 1.0 (95% CI 0.6-1.5) and malformations; 1.2 (95% CI 0.9-1.7)., Conclusion: Cancer in pregnancy increases the risk of induced abortion and planned premature birth. Neonates born to mothers with cancer in pregnancy had an increased risk of neonatal morbidity and mortality, presumably due to prematurity., Tweetable Abstract: Cancer in pregnancy is associated with an increased risk of premature birth leading to adverse neonatal outcomes., (© 2022 John Wiley & Sons Ltd.)

Objective: To study the risk of a second malignant neoplasm (SMN) and mortality in patients with rheumatoid arthritis (RA) with a history of a primary cancer diagnosis and treated with biological disease-modifying antirheumatic drugs (bDMARD)., Methods: Among patients with RA (n=15 286) registered in the DANBIO Register during 2000-2011, 1678 had a primary cancer according to the Danish Cancer Registry. HRs for SMN and death were calculated., Results: During follow-up there were 279 patients with RA contributing person-years to the bDMARDs use before their primary cancer diagnosis, 220 to the only after , 92 to the both before and after, while 1203 patients with RA contributed to the non-use strata. Ever use of bDMARDs was associated with a HR of 1.11 (95% CI 0.74 to 1.67) for developing a SMN compared with non-use (cancer site adjusted). The HR for death associated with bDMARD use before the primary cancer diagnosis was increased 1.53 (95% CI 1.13 to 2.09). After further adjustment for extent of the primary cancer, the HR for death was 1.20 (95% CI 0.88 to 1.63) for bDMARDs use before cancer, 1.36 (95% CI 0.78 to 2.39) for bDMARD use only after cancer and 1.22 (95% CI 0.70 to 2.13) for use both before and after the cancer., Conclusions: Among patients with RA with a history of cancer, treatment with bDMARDs was not associated with increased risk of SMN. No clear conclusion can be drawn regarding mortality in bDMARD-treated patients with RA., Competing Interests: Competing interests: LD: have received speaking fees outside the submitted work from UCB, MSD and Janssen pharmaceutica; IMJ: Roche Pharmaceuticals; LEK: Pfizer, AbbVie, Amgen, UCB, Celgene, BMS, Biogen, Forward Pharma, MSD, Novartis, Eli Lilly and Janssen Pharmaceuticals; MLH: AbbVie, BMS, MSD, Pfizer, Orion, Novartis, Biogen, Eli Lilly, Celltrion., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries., Methods: From the national cancer registries of Denmark, Iceland and Sweden, we identified 20 361 1-year survivors of cancer diagnosed before the age of 20 between the start of cancer registration in the 1940s and 1950s through 2008; 125 794 comparison subjects, matched by age, gender and country, were selected from national population registers. Study subjects were linked to the national hospital registers. Standardised hospitalisation rate ratios (SHRRs) and absolute excess risks (AERs) were calculated., Results: Childhood cancer survivors had a significantly increased SHRR of 1.4 (95% CI 1.3 to 1.5) of all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3.6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjögren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1.6), renal tumours (1.6) and central nervous system neoplasms (1.4)., Conclusions: Childhood cancer survivors are at increased risk for certain types of autoimmune diseases. These findings underscore the need for prolonged follow-up of these survivors., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To investigate the risk of virus-associated cancer in female arthritis patients ever treated with biological DMARDs (bDMARDs) compared with never bDMARD-treated patients and ever and never treated with bDMARD compared with the general population., Methods: This was a cohort study that included 13 905 female patients with RA (72%), PsA (12%), AS (4%) or other arthritides (12%) identified in the DANBIO registry. Ever (n = 5647) and never (n = 10 331) bDMARD-treated patients were followed for virus-associated cancers during 2000-11 by linkage to the Danish Cancer Registry. Hazard ratios and standardized incidence ratios (SIRs) were calculated., Results: In total, 24 and 32 virus-associated cancers were identified among ever and never bDMARD users, respectively (hazard ratio = 0.9, 95% CI: 0.7, 1.2). Oropharyngeal (n = 3, SIR = 4.0, 95% CI: 1.3, 12.4) and anal (n = 2, SIR = 2.5, 95% CI: 0.6, 10.0) cancer only occurred among bDMARD-treated patients. SIR was not increased for cervical cancer, either in ever or never bDMARD-treated patients. SIRs for Hodgkin's and non-Hodgkin's lymphomas were increased in never bDMARD-treated patients (SIR = 2.5, 95% CI: 1.5, 4.0)., Conclusion: bDMARD therapy was not associated with an overall excess of virus-associated cancers in female arthritis patients. The observed increased occurrence of oropharyngeal cancer needs further investigation. Lymphoma incidence was increased in patients unexposed to bDMARD treatment., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis.

Background: Cardiovascular disease has emerged as a serious late effect in survivors of adolescent and young adult cancer, but risk has not been quantified comprehensively in a population-based setting., Methods: In the Danish Cancer Registry, we identified 43153 1-year survivors of cancer diagnosed at ages 15 to 39 years (1943-2009) and alive in 1977; from the Danish Civil Registration System, we randomly selected a comparison cohort of the same age and sex. Subjects were linked to the Danish Patient Register, and observed numbers of first hospitalizations for cardiovascular disease (International Classification of Diseases, Tenth Revision codes I10-I79) were compared with the expected numbers derived from the comparison cohort. We calculated the absolute excess risks attributable to status as a survivor of cancer and standardized hospitalization rate ratios (RRs). All statistical tests were two-sided., Results: During follow-up, 10591 survivors (24.5%) were discharged from the hospital with cardiovascular disease, whereas 8124 were expected (RR = 1.30; 95% confidence interval [CI)] = 1.28 to 1.33; P < .001). The absolute excess risks were 400 and 350 extra cases of cardiovascular disease per 100000 person-years for people aged 20 to 59 and 60 to 79 years at discharge, respectively. Survivors of Hodgkin lymphoma experienced high risks for being hospitalized with valvular disease (RR = 12.2; 95% CI = 9.9 to 15.0; P < .001). Survivors of leukemia had high risks for cerebral hemorrhage (RR = 10.3; 95% CI = 5.5 to 19.1; P < .001) and cardiomyopathy (RR = 8.6; 95% CI = 4.3 to 17.3; P < .001)., Conclusions: Survivors of adolescent and young adult cancer are at increased risk for cardiovascular disease throughout life, although each main type of adolescent and young adult cancer had its own risk profile., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To investigate the incidence of cancer in arthritis patients treated with or without TNFα inhibitors (TNF-I)., Methods: Arthritis patients from the DANBIO database were followed-up for cancer in the Danish Cancer Registry during 2000-2008., Results: Hazard ratio for cancer overall was 1.02 (95% confidence interval (CI) 0.80-1.30) in 3347 TNF-I-treated RA patients compared to non-treated. Excess among TNF-I-treated was found for colon cancer (HR 3.52 (95%CI 1.11-11.15), whereas 6 and 0 ovarian cancer cases were observed in treated and non-treated patients, respectively. Compared to the general population, TNF-I-treated RA patients had increased risk for cancer overall, cancer in lymphatic-haematopoietic tissue and non-melanoma skin cancer, while non-RA patients had no increase in overall cancer risk., Conclusions: Our results suggest that TNF-I therapy in routine care is not associated with an overall excess of cancer in arthritis patients, but observed increased risks of colon and ovarian cancer need further investigation.

Objective: To investigate whether patients with WG have an increased risk of malignancies prior to and/or around the time of the vasculitis diagnosis, as suggested by previous studies., Methods: A total of 293 WG patients were included in the study. Ten gender- and age-matched controls were selected randomly for each patient from the Danish Central Population Register. Information on malignancies was obtained through the Danish Cancer Registry. Occurrence of malignancies before WG diagnosis among patients and before WG diagnosis of their matched case among controls (reference date) was compared by calculation of prevalence odds ratios (OR)., Results: Twenty-six patients were diagnosed with cancer before WG, while 194 controls were diagnosed with cancer before the reference date (OR 1.4; 95% CI 0.9, 2.2). Among specific malignancies, a significantly increased prevalence was found for testis cancer (OR 6.4; 95% CI 1.1, 38) based on two patients, who developed testis cancer >10 years before WG. The overall prevalence of malignancies diagnosed <2 years before WG was not significantly increased (OR: 1.6; 95% CI: 0.8, 3.4), but non-melanoma skin cancer occurred with an increased prevalence within this time interval (OR 4.0; 95% CI 1.4, 12)., Conclusions: We did not find clear evidence of an increased prevalence of preceding cancer in our WG cohort, indicating that shared risk factors are of minor importance for the excess of malignancies that occur in WG patients after the vasculitis diagnosis. Furthermore, our current and previously reported latency analyses do not substantiate that serious malignancies play a significant role in the pathogenic events that trigger development of WG.

Introduction: The use of anti-tumour necrosis factor (anti-TNF) therapy is increasing in the treatment of rheumatoid arthritis (RA), spondyloarthropathy, psoriasis and inflammatory bowel disease. It is being debated whether treatment of patients with rheumatic diseases with anti-TNF therapy is associated with an increased cancer incidence., Material and Methods: A descriptive study of cancer cases among 3,688 patients with rheumatic diseases who received anti-TNF therapy was performed. The patients were identified in the nationwide database DANBIO and had a total number of treatment years of 6,092 years. All cancer cases were identified and the cancer diagnoses were subsequently confirmed by medical record review., Results: A total of 30 cancers in 28 of 3,688 patients were registered in the DANBIO after initiation of anti-TNF therapy in the period from October 2000 to June 2007. Among these six men and 20 women had RA, and two men had Morbus Becterew. The following cancer types were observed: malignant lymphoma 2 (7%), lung 4 (13%), plicae vocalis 2 (7%), breast 4 (13%), pancreatic 3 (10%), colorectal 2 (7%), prostate 1 (3%), malignant melanoma 3 (10%) and non-melanoma skin cancer 9 (30%)., Conclusion: In our descriptive study from the nationwide database DANBIO, a total of 30 cancers were observed in 3,688 patients with rheumatic diseases within a cumulated period of treatment with anti-TNF of 6,092 years. Follow-up for anti-rheumatic and adverse effects in patients in the DANBIO database will continue. Future studies must reveal whether anti-TNF therapy is associated with an increased cancer risk. Planned Danish studies will include relevant control groups and adjustment for confounders.

Low hormone levels among persons with osteoporosis may decrease risk of some cancers. Other osteoporosis risk factors, such as smoking and alcohol consumption, however, may increase risk. As these deleterious factors are more often associated with osteoporosis diagnosed prior to age 70 years, cancer risk may be higher in these younger persons than in the general population. To examine this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were identified in the Danish Inpatient Register. Linkage to the Danish Cancer Registry identified all cancer outcomes through 2003. Standardized incidence ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare cancer incidence in the cohort with that in the general population. Persons diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11, 95%CI = 1.04-1.19; men: SIR = 1.31, 95%CI = 1.13-1.50) due, in part, to increased risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung. Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91, 95%CI = 0.87-0.96; men: SIR = 0.89, 0.77-1.01) due, in part, to decreased risks of breast, endometrial, colon, rectal and brain cancers in women and prostate cancer in men. These results suggest that risk factors associated with earlier onset osteoporosis may be associated with increased risk of cancer. Conversely, factors associated with later onset osteoporosis may be related to a decreased risk of cancer.

Objective: To describe the incidence of malignancies in a cohort of Danish patients with Wegener's granulomatosis (WG) and to investigate the cancer risk associated with cyclophosphamide (CYC) -therapy in WG., Methods: In total, 293 patients diagnosed with WG between 1973 and 1999 were studied. Cancer incidence in the cohort was assessed through 2003 by linkage to the Danish Cancer Registry and compared to that of the general population by calculation of standardized incidence ratios (SIR). Analyses were stratified according to treatment with low cumulative CYC doses (< or = 36 g) and high doses (> 36 g, corresponding to treatment with 100 mg CYC/day for > 1 year)., Results: Fifty cancers occurred during 2121 person-years of followup (SIR of cancer of 2.1, 95% CI 1.5-2.7). Significantly increased SIR were observed for acute myeloid leukemia (AML; SIR 19.6, 95% CI 4.0-57), bladder cancer (SIR 3.6, 95% CI 1.2-8.3), and non-melanoma skin cancers (SIR 4.7, 95% CI 2.8-7.3). Leukemias and bladder cancers were diagnosed 6.9-18.5 years after initiation of CYC therapy. The risk of these malignancies was not increased for patients who never received CYC or for patients treated with cumulative CYC doses < or = 36 g. In contrast, high risks of AML (SIR 59.0, 95% CI 12-172) and bladder cancer (SIR 9.5, 95% CI 2.6-24) were observed for patients treated with cumulative CYC doses > 36 g., Conclusion: Treatment with high cumulative CYC doses implies a substantial risk of late-occurring, serious malignancies in WG. Patients with WG should be monitored for development of cancer for several decades after cessation of CYC therapy. These findings emphasize the need for development of new treatment regimens in WG.

Objective: To analyze whether fibromyalgia (FM) and FM-like symptoms are related to an increased incidence of cancer., Methods: We identified 1361 patients referred on suspicion of FM in the period 1984-99 from hospital records. Following the American College of Rheumatology (ACR) criteria, patients were divided into subgroups with and without confirmed FM. The cohort was followed to the end of 1999 and linked to the files of the Danish Cancer Register. Site-specific standardized incidence ratios (SIR) were calculated., Results: We found no association between FM and cancer in 1132 female patients with confirmed FM at our institution (SIR 1.2, 95% CI 0.8-1.8). In 106 women referred for muscle pain and/or tenderness who did not meet the criteria for FM, an increased overall SIR was observed (SIR 2.5, 95% CI 1.2-4.6), with increased risk for breast cancer (SIR 4.8, 95% CI 1.6-11.3) and lymphatic and hematological cancers (SIR 10.6, 95% CI 1.2-38.2). There were 4 lung cancers in 84 men with confirmed FM (SIR 12.6, 95% CI 3.4-32.4)., Conclusion: Neither confirmed FM nor those without confirmed FM predicted cancer. An increased risk of breast cancer was found among those who did not meet the ACR criteria for FM. These patients should be investigated if they develop any new or warning symptoms of malignancy, and treating physicians should be vigilant with screening procedures such as mammography.

Cancer risk in children born before term has been assessed in a large number of case-control studies but very rarely in cohort studies. We carried out a cohort study of 35 178 children with the diagnosis immaturity at birth in the Hospital Discharge Register during 1977-89. The children were followed for cancer in the Danish Cancer Registry until 1994 and comparisons were made with incidence rates for all children in Denmark. The 64 observed cases of childhood cancer in the cohort corresponded closely to the expected number {standardised incidence ratio (SIR) = 1.03; [95% confidence interval (CI) 0.80, 1.32]}. The only cancer site with an observed number that deviated significantly from the expected number was central nervous system (CNS) tumours (26 cases observed; SIR = 1.57; [95% CI 1.02, 2.30]) in particular medulloblastoma (9 cases observed; SIR = 3.1; [95% CI 1.4, 5.9]). In a nested case-control study of the CNS tumours, we found that more cases than controls had been exposed to diagnostic X-rays, but the result was not significant. Surprisingly, for those born before term, the risk of CNS tumours increased with increasing gestational age in the nested case-control data. Our results are in line with previous evidence that children born before term are not at increased risk for childhood cancer in general. An explanation behind the excess of CNS tumours could not be identified, but the effect of diagnostic X-rays in newborns may deserve further attention.

Background: Fever of unknown origin is associated with cancer, but the tumour types most commonly involved and the prognostic implications of this relation have not been studied. We aimed to assess the risk of cancer and survival after hospital admission for fever of unknown origin in a nationwide Danish follow-up study., Methods: We linked the Danish national registry of patients and the nationwide cancer registry, and assessed cancer risk for 43,205 patients discharged for the first time from Danish hospitals after admission for fever of unknown origin during 1977-97. We compared cancer frequency with that expected on the basis of cancer incidence in the general population, and survival of patients with cancer who had had fever of unknown origin with that of controls (ie, patients with cancer matched for cancer site, age at time of cancer diagnosis, and year of cancer diagnosis)., Findings: Median follow-up was 6.3 years (IQR 2.7-12.3). During the first year of follow-up, 399 cancers were diagnosed in those who had had fever of unknown origin (standardised incidence ratio 2.3 [95% CI 2.1-2.5]). These individuals had an increased risk of developing cancer--in particular haematological malignant disease; sarcoma; and cancers of the liver, brain, kidney, colon, and pancreas. After 1 year of follow-up, individuals had an increased risk of developing haematological malignant disease and cancers of the liver, brain, and kidney. A slightly higher proportion of people diagnosed with cancer within 1 year of hospital discharge after fever of unknown origin had distant metastases compared with controls (101 [34%] of 294 vs 819 [28%] of 2907; prevalence ratio 1.2 [95% CI 1.0-1.4], and had worse survival than did controls (mortality rate ratio 1.4 [95% CI 1.2-1.6])., Interpretation: Hospital admission for fever of unknown origin is a marker of occult cancer and is associated with a poor outlook.

We investigated the cancer risk of patients hospitalized for schizophrenia in a nationwide cohort study. All 22766 adults admitted for schizophrenia, ICD-8 295, in Denmark between 1969 and 1993 were followed up for cancer through 1995. The incidence of site-specific cancers was compared with national incidence rates, adjusted for sex, age and calendar time. The risk for cancer was increased for both men and women during the first year of follow-up. When the first year of follow-up was excluded, the risk for all tobacco-associated cancers and for prostate and rectal cancers was reduced for male patients with schizophrenia. The standardized incidence ratio (SIR) of lung cancer was marginally reduced (SIR, 0.86; 95% CI: 0.65, 1.02) for male patients with schizophrenia; this was due, however, to a reduction in risk for older patients. An increased risk for breast cancer found for female patients with schizophrenia (SIR, 1.20; 95% CI: 1.05, 1.38) should be interpreted with caution, given the high proportion of nulliparous women with schizophrenia in Denmark. The data might support reduced risks for prostate and rectal cancer among male patients with schizophrenia, whereas a changing smoking pattern might explain the reduced risk for tobacco-related cancers.

Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the period 1977-98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinson's disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.

We examined the risk of cancer and survival in a cohort of patients hospitalised with herpes zoster between 1977 and 1996, drawn from the Danish National Registry of Patients. Through linkage with the Danish Cancer Registry, we compared the observed number of cancers with the expected number on the basis of national age-, gender-, and site-specific incidence rates. The survival of herpes zoster patients with cancer was compared with that of non-herpes zoster patients with cancer. Among the 10 588 patients hospitalised with herpes zoster whom we identified, 1427 cancers were observed compared with 1239 expected (relative risk=1.2, 95% confidence interval 1.1-1.2). The risk was substantially elevated during the first year of follow-up, mainly for haematological cancer. Patients with cancer within 1 year of follow-up had a higher prevalence of distant metastases than controls, although the mortality was similar. For those with haematological cancer, however, the mortality was higher for herpes zoster patients than for controls. Haematological cancer following hospitalisation for herpes zoster has a poorer prognosis than in non-herpes zoster patients.

Objective: This study attempted to determine whether a genetic protection against cancer might be manifest in parents of offspring with schizophrenia., Method: Using data from the Danish Central Population Registry, the authors identified 1,999,072 parents of offspring born after 1935. By linking this nationwide population-based parent cohort to the Danish Psychiatric Central Register, they identified 19,856 parents of offspring with schizophrenia. Follow-up for cancer in the Danish Cancer Registry began on the date of birth of the oldest child or April 1, 1969, and ended on the date of cancer diagnosis, death, or Dec. 31, 1997, yielding a total of 48,343,430 person-years at risk and 211,681 cases of cancer. The relative risk for cancer among parents with schizophrenic offspring compared to parents with no schizophrenic offspring was estimated by Poisson regression analysis and adjusted for age, period, and number of children., Results: The risk for all cancer was 1.01 for fathers and 1.00 for mothers of schizophrenics. Mothers of schizophrenic patients had an increased risk of 1.20 for lung cancer and a nonsignificant risk of 1.14 for tobacco-related cancers combined. Apart from a reduced risk for leukemia in both mothers and fathers of schizophrenics, there was no difference in risk for any other cancer., Discussion: This study does not confirm a previously reported reduced risk for cancer in parents of schizophrenic patients and provides no support for genetic protection against cancer in families with schizophrenia.

Background: We investigated whether children and adolescents who survive cancer are at increased risk for psychiatric hospitalization., Methods: In a nationwide, population-based, retrospective cohort study, 3710 persons who survived at least three years after a diagnosis of cancer in childhood or adolescence in the period from 1943 to 1990, and who were alive on January 1, 1970, or were born after that date, were identified in the Danish Cancer Registry. This population was followed up for psychiatric hospitalization from January 1, 1970, through 1993 by linkage with the Danish national Psychiatric Central Register. The number of expected cases was based on the national rates of hospitalization for psychiatric disease., Results: Among the 3710 survivors of cancer in childhood or adolescence, there was a total of 88 psychiatric hospitalizations. The risk of hospitalization for any psychiatric disease was higher among the survivors than in the general population, but the excess risk was restricted to survivors of brain tumor (the standardized hospitalization ratio [SHR], corresponding to the ratio of observed to expected cases of hospitalization for psychiatric disease, was 1.8; 95 percent confidence interval, 1.5 to 2.2). An increased risk of psychoses of somatic, cerebral causes (SHR, 7.7; 95 percent confidence interval, 4.1 to 13.2), psychiatric disorders in somatic disease (SHR, 5.1; 95 percent confidence interval, 2.5 to 9.1), and schizophrenia and related disorders (SHR, 2.4; 95 percent confidence interval, 1.2 to 4.4) was observed among survivors of brain tumor. There was no evidence of a significantly increased risk of major depression., Conclusions: The risk of hospitalization for a psychiatric disorder is not increased among survivors of cancer in childhood or adolescence, except among survivors of brain tumor., (Copyright 2003 Massachusetts Medical Society)

There is increasing evidence of an inverse association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of colorectal cancer. However, data regarding other cancer sites are limited. Using data from the population-based North Jutland Prescription Database and the Danish Cancer Registry, we compared cancer incidence among 172 057 individuals prescribed nonaspirin NSAIDs with expected incidence (based on county-specific cancer rates) during a 9-year study period. A total of 6081 incident cancer cases were diagnosed among NSAID users vs 5722 expected (standardised incidence ratio (SIR) 1.1, 95% confidence interval (CI)1.0-1.1). The SIRs for colon and rectal cancer among persons who obtained 10 or more prescriptions were 0.7 (95% CI 0.6-0.9) and 0.6 (95% CI 0.4-0.9), respectively. Similarly, reduced risk estimates were found for stomach (SIR 0.7, 95% CI 0.4-1.1) and ovarian cancer (SIR 0.7, 95% CI 0.4-1.0). Standardised incidence ratios for other cancers among those with 10 or more prescriptions tended to be close to 1.0, except for lung, kidney, and prostate cancers with SIRs of 1.3 (95% CI 1.1-1.6), 1.4 (95% CI 0.9-2.1), and 1.6 (95% CI 1.3-2.0), respectively. We found protective associations of NSAIDs against colon, rectal, stomach, and ovarian cancer. Reasons for the increased risk for some cancer sites are not clear.

Background: Individuals with Down syndrome (DS) have a predisposition to leukemia and possibly other cancers and excess mortality from other conditions, but information on the magnitude of risk associated with specific cancers or causes of death is sparse., Methods: Mortality experience and cancer incidence were evaluated in a combined cohort of 4872 individuals with a hospital discharge diagnosis of DS in Sweden (1965-1993) or Denmark (1977-1989) by linkage to national cancer and vital statistics registries. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were estimated by comparison with age, sex, and calendar-year expected values., Results: Individuals with DS had an increased risk of incident acute lymphocytic (SIR, 24.2; 95% confidence interval [CI], 15.2-36.6; n = 22) and acute nonlymphocytic (SIR, 28.2; 95% CI, 15.7-48.3; n = 14) leukemias. Risks of testicular cancer (SIR, 3.7; 95% CI, 1.0-9.4; n = 4) and liver cancer (SIR, 6.0; 95% CI, 1.2-17.5; n = 3) were also elevated. Individuals with DS also experienced elevated mortality attributed to stomach cancer (SMR, 6.4; 95% CI, 1.7-16.4; n = 4), dementia and Alzheimer disease (SMR, 54.1; 95% CI, 27.9-94.4), epilepsy (SMR, 30.4; 95% CI, 13.9-57.7), ischemic heart disease (SMR, 3.9; 95% CI, 2.7-5.4), other heart disease (SMR, 16.5; 95% CI, 11.0-23.7), cerebrovascular disease (SMR, 6.0; 95% CI, 3.5-9.6), infectious diseases (SMR, 12.0; 95% 6.0-21.4), and congenital anomalies (SMR, 25.8; 95% CI, 21.0-31.4)., Conclusions: Individuals with DS have a substantially increased risk of mortality due to specific causes and may have an elevated risk of other incident cancers in addition to leukemia. These results provide clues regarding chromosome 21 gene involvement in diseases that complicate DS and are important for disease detection and care of affected individuals.

The extremely high risk reported for some types of cancer among patients with common variable immunodeficiency (CVID) is based on a limited number of investigations. Therefore, we examined the risks for cancer among 562 Danish and Swedish patients with CVID or IgA deficiency and 2071 relatives in 1958-96. The patients were identified through an Immunodeficiency Register and hospital records, while the relatives were traced through population registers. Cancer incidence was assessed by linkage to the Cancer Registries and compared with that in the general population. Among 386 patients with IgA deficiency, the incidence of cancer was not increased (standardized incidence ratio (SI) = 1.0); but two cases of stomach cancer were found, resulting in a non-significant increase in risk (SIR = 5.4; 95% CI = 0.7-19.5). Among 176 patients with common variable immunodeficiency (CVID), the incidence of cancer at all sites combined was increased (SIR = 1.8; 95% CI = 1.0-2.9), which was due mainly to significant excesses of malignant lymphoma (obs = 4; SIR = 12.1; 95% CI = 3.3-31.0) and of stomach cancer (obs = 3; SIR = 10.3; 95% CI = 2.1-30.2). Among the 626 relatives of patients with CVID, no increase in risk was found for these types of cancer or for cancer overall (obs = 53; SIR = 1.0; 95% CI = 0.8-1.3). Our data show that the risks for malignant lymphoma and stomach cancer among patients with CVID may be lower than reported previously. The absence of an increased risk among relatives suggests that the increased cancer morbidity in patients with CVID is related to the immunodeficiency per se rather than to specific genetic traits shared with their relatives.

The authors investigated the cancer risk of patients hospitalized for depression in a nationwide Danish cohort study. All 89,491 adults in Denmark who had been admitted to a hospital with depression, as defined in the International Classification of Diseases, Eighth Revision, between 1969 and 1993 were identified. There were 1,117,006 person-years of follow-up. Incidence rates of all cancers and of site-specific cancers were compared with national incidence rates for first primary cancers, with data being adjusted for sex, age, and calendar time. A total of 9,922 cases of cancer were diagnosed in the cohort, with 9,434.6 having been expected; this yielded a standardized incidence ratio of 1.05 (95% confidence interval (CI): 1.03, 1.07). The risk of cancer was increased for the first year after hospital admission, with brain cancer especially occurring more frequently than expected. When the first year of follow-up was excluded, the increase was attributable mainly to an increased risk of tobacco-related cancers: Standardized incidence ratios for non-tobacco-related cancers were 1.00 (95% CI: 0.97, 1.03) after 1-9 years of follow-up and 0.99 (95% CI: 0.95, 1.02) after 10 or more years of follow-up. These data provide no support for the hypothesis that depression independently increases risk of cancer, but they emphasize the deleterious effect that depression can have on lifestyle factors.

Objective: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark., Methods: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977-1993; Sweden 1965-1993) were linked to tumor registry data for up to 15-28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly., Results: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5. 95% CI = 1.3-1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.62.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2-17.4), colon (SIR = 2.6, 95% CI = 1.6-3.8), and rectum (SIR = 2.5, 95% CI= 1.3-4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI= 1.2-5.0). thyroid (SIR = 3.7, 95% CI = 1.8-10.9), kidney (SIR = 3.2, 95% CI = 1.6-5.5), and bone (SIR= 13.8, 95% CI= 1.7-50.0)., Conclusions: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-I system in the etiology of various cancers.

Background: A recent observational study suggested that the use of angiotensin-converting enzyme (ACE) inhibitors protects against cancer in general and against breast and female reproductive tract cancers in particular. To explore these hypotheses, the authors examined cancer risk among users of ACE inhibitors in North Jutland County, Denmark., Methods: Using data from the population-based Prescription Database of North Jutland County and the Danish Cancer Registry, cancer incidence among 17,897 individuals prescribed ACE inhibitors was compared with expected incidence based on county specific cancer rates during an 8-year study period with a mean follow-up of 3.7 years. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. In addition, the authors performed a direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers (n = 47,579 individuals) by means of a Cox proportional hazards model., Results: Overall, 909 cancer cases were observed among users of ACE inhibitors, with 846 expected based on general population rates, yielding an SIR of 1.07 (95% CI, 1.01-1.15). No risk reductions were observed for cancers of the breast and female reproductive tract, whereas nonsignificantly decreased SIRs were observed for cancers of the esophagus, stomach, and liver. Cancer of the kidney was found in significant excess (SIR, 1.6; 95% CI, 1.1-2.2). Stratification by duration of follow-up or number of prescriptions revealed no apparent trends, except for a tendency toward decreasing risk with increasing length of follow-up for smoking-related cancers. The direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers yielded results comparable to those derived from the comparison with the general population, with a hazard ratio for cancer overall of 1.01 (95% CI, 0.93-1.09)., Conclusions: This large, population-based cohort study did not confirm a protective effect of ACE inhibitors on the development of cancer. The excess of kidney cancer observed likely reflects a correlation between hypertension and kidney cancer. Further investigation is needed to evaluate the long-term effects of ACE inhibitors beyond the observation period of this and previous studies. Also, the suggestive evidence of decreased risks for upper digestive system cancers and for smoking-related cancers over time may warrant additional investigation., (Copyright 2001 American Cancer Society.)

Objective: Energy restriction reduces the incidence of malignant tumors in experimental animals, but evidence for a similar effect in humans is lacking. To test the hypothesis in humans, we investigated cancer incidence among patients with anorexia nervosa, who have had an extremely low intake of calories for prolonged periods of their lives., Methods: Patients with anorexia nervosa (2151 women and 186 men) during 1970-1993 were identified in the population-based Danish Psychiatric Case Register and the National Registry of Patients. The cohort was linked to the Danish Cancer Registry, and cancer incidence among cohort members was compared with that of the general population., Results: The overall cancer incidence among women with anorexia nervosa was reduced by a factor of 0.80 (95% confidence interval 0.52-1.18) below that of the general population on the basis of 25 observed and 31.4 expected cases. Among men, two cases of cancer were observed, both confined to the brain, whereas 0.2 cases were expected., Conclusions: The finding of a slight reduction in cancer risk among women with anorexia nervosa may support the theory that a low-energy diet may decrease tumor development in humans. However, longer follow-up and control for confounding factors are needed to obtain more convincing evidence.

Background: Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis., Methods: We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date., Findings: We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis., Interpretation: Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

Background: Little is known about the prognosis of cancer discovered during or after an episode of venous thromboembolism., Methods: We linked the Danish National Registry of Patients, the Danish Cancer Registry, and the Danish Mortality Files to obtain data on the survival of patients who received a diagnosis of cancer at the same time as or after an episode of venous thromboembolism. Their survival was compared with that of patients with cancer who did not have venous thromboembolism (control patients), who were matched in terms of type of cancer, age, sex, and year of diagnosis., Results: Of 668 patients who had cancer at the time of an episode of deep venous thromboembolism, 44.0 percent of those with data on the spread of disease (563 patients) had distant metastasis, as compared with 35.1 percent of 5371 control patients with data on spread (prevalence ratio, 1.26; 95 percent confidence interval, 1.13 to 1.40). In the group with cancer at the time of venous thromboembolism, the one-year survival rate was 12 percent, as compared with 36 percent in the control group (P<0.001), and the mortality ratio for the entire follow-up period was 2.20 (95 percent confidence interval, 2.05 to 2.40). Patients in whom cancer was diagnosed within one year after an episode of venous thromboembolism had a slightly increased risk of distant metastasis at the time of the diagnosis (prevalence ratio, 1.23 [95 percent confidence interval, 1.08 to 1.40]) and a relatively low rate of survival at one year (38 percent, vs. 47 percent in the control group; P<0.001)., Conclusions: Cancer diagnosed at the same time as or within one year after an episode of venous thromboembolism is associated with an advanced stage of cancer and a poor prognosis.

Most studies on cancer incidence after breast implantation have focused on breast cancer, while the risk of cancers at other sites has been less well investigated. We examined cancer incidence among 1,653 women who underwent cosmetic breast implant surgery at private clinics of plastic surgery in Denmark and 1,736 women attending the same clinics for other reasons during the period 1973-1995. Furthermore, we updated previously reported results among 1,114 women who received implants for cosmetic indications at public hospitals. All women were followed for cancer through the Danish Cancer Registry. In comparison with the general female population, the overall standardized incidence ratio (SIR) for cancer among women who received implants in private clinics was 1.65 [95% confidence interval (CI) = 1.17-2.27]. This elevated SIR reflected increased incidence ratios for almost all major cancer sites; however, only for non-melanoma skin cancer was there an excess of more than 2 cases. No significant excess of cancer was observed among women who received implants in public hospitals (SIR = 1.10, 95% CI = 0.76-1.52) or among women attending the private clinics for other problems (SIR = 1.10, 95% CI = 0.78-1.52). The SIRs for breast cancer after breast implantation were 1.1 (95% CI = 0.5-2.2) among private clinic patients and 0.9 (95% CI = 0.4-1.7) among public hospital patients. The overall findings of these 2 implant cohorts and results from other investigations suggest that cancer risk is probably not increased among women receiving cosmetic breast implants. The inconsistent results for private clinics and public hospitals are likely related to selection bias and confounding among the private clinic patients, but our data did not permit exploration of these possibilities. Further research into the determinants of these inconsistencies is warranted., (Copyright 2000 Wiley-Liss, Inc.)

Background: Data regarding the association between the use of calcium channel blockers and cancer risk have been conflicting. In the current study, the authors examined the cancer risk and mortality in users of calcium channel blockers in North Jutland County, Denmark., Methods: The authors conducted a cohort study using record linkage between a population-based prescription database, the Danish Cancer Registry, and the Danish Death Registry including 23, 167 users of calcium channel blockers who received >/=2 prescriptions between January 1, 1989 and December 31, 1995. The authors calculated the standardized incidence ratios and standard mortality ratios for cancer, along with corresponding 95% confidence intervals (95% CI)., Results: Overall, 967 incident cases of cancer occurred, resulting in a standardized incidence ratio of 1.04 (95% CI, 0.98-1.11). There was a slightly elevated nonsignificant risk of tobacco-related cancer. No increased risk of breast or colon carcinoma was observed. The cancer mortality was close to that expected in the background population (standardized mortality ratio of 0.97; 95% CI, 0.89-1.04)., Conclusions: This large-scale, population-based cohort study adds to the increasing evidence indicating no substantial association between the use of calcium channel blockers and the incidence rate of cancer or cancer mortality., (Copyright 2000 American Cancer Society.)

We report a nationwide study based on a cohort of patients with a thromboembolic event (TE) defined as deep venous thrombosis and/or pulmonary embolism identified from the Danish National Registry of Patients from 1977 to 1993. Cancer occurrence in the cohort was determined by linkage to the Danish Cancer Registry. Expected number of cancer cases was estimated from age, sex and site-specific incidence rates. A total of 26,653 TE-cases were identified. We observed 1737 cases of cancer versus 1371 expected (SIR 1.3; 95% CI, 1.21 to 1.33). The risk was particularly high during the first months of follow-up, but declined rapidly hereafter to a constant level slightly above 1.0 one year after the TE. Forty percent of patients diagnosed with cancer within one year from the hospitalization for TE had distant metastases at the time of cancer diagnosis. The observed risk pattern provides evidence that most often a preclinical cancer gives rise to a subsequent TE. An aggressive search for hidden cancer in patients with TE is not warranted.

Antidepressants appear to promote tumor growth in experimental studies; however, results from epidemiologic studies are inconclusive. We used a population-based cohort study to estimate the incidence of cancer after antidepressant treatment in 39,807 adult users of antidepressants identified in the Prescription Database of the County of North Jutland, Denmark between January 1, 1989 and December 31, 1995. Information on cancer occurrence was obtained from the Danish Cancer Registry. We categorized exposure according to use of tricyclic antidepressants, tetracyclic antidepressants, selective serotonin reuptake inhibitors, or monoamine oxidase inhibitors. In the follow-up period beginning 1 year after first known prescription, there were 966 cancers among users of antidepressants; our population estimate suggested an expected number of 946 for an overall standardized incidence ratio of 1.0 (95% confidence interval = 1.0-1.1). Users of tricyclic antidepressants had an excess of non-Hodgkin's lymphoma, with the risk increasing with the number of prescriptions of tricyclic antidepressants. The standardized incidence ratio was 2.5 (95% confidence interval, 1.4-4.2) for those with five or more prescriptions. Our results provide little evidence that antidepressants promote cancer at other sites, except for a possible effect of tricyclic antidepressants and tetracyclic antidepressants on non-Hodgkin's lymphoma.

To assess the cancer risk of monoclonal gammopathy of undetermined significance (MGUS) we identified 1229 cases of MGUS in the period 1978 to 1993. Data on cancer occurrence in the MGUS cohort were obtained from the Danish Cancer Registry. The expected numbers of cancer cases were calculated from age-, sex-, county-, and period-specific cancer incidence rates. In the MGUS cohort 64 new cancers with a known association with M-components were diagnosed versus 5.0 expected giving a standardized incidence ratio (SIR) of 12.9 (95% confidence interval, 9.9-16.5). The relative risks of developing multiple myeloma (SIR 34.3), Waldenström's macroglobulinemia (SIR 63.8), and non-Hodgkin's lymphoma (SIR 5.9) were significantly increased and independent of time passed from detection of the M-component. The relative risk of chronic lymphocytic leukemia was not significantly increased, SIR 2.7 (0.5-7. 7). Among cancer sites without known association with M-components 141 cases were observed versus 94.6 expected giving a SIR of 1.5 (1. 3-1.8). This enhanced risk was seen for several non-hematological cancer sites but for most cancer sites the risk was dependent on time passed from detection of the M-component, indicating a bias rather than a causal role of MGUS., (Copyright 2000 Wiley-Liss, Inc.)

Objective: It was our aim to evaluate the hypothesis that molar pregnancy is a marker of increased risk for cancer., Study Design: This was a nationwide cohort study of 1520 women, identified from the Danish National Register of Patients, in whom a molar pregnancy was diagnosed during the period 1977-1992 and of 1295 male partners of these women, traced in the Danish Central Population Register., Results: Linkage of the female roster with the Danish Cancer Registry through 1994 revealed 19 cases of gestational choriocarcinoma, whereas 0.04 was expected from the rates for the general population. Twenty cases of cancers of other types were observed with 24.9 expected (standardized incidence ratio, 0.8; 95% confidence interval, 0.5-1.2), but no specific type of cancer other than gestational choriocarcinoma occurred at a rate significantly different from that expected. Among the 1295 male partners notified in the Central Population Register, a total of 22 cancers were observed with 21.9 expected (standardized incidence ratio, 1.0; 95% confidence interval, 0.7-1.5)., Conclusion: Molar pregnancy is not associated with an increased risk for cancer other than gestational carcinoma.

Cancer incidence and mortality risks were evaluated in a combined cohort of patients who were hospitalized for porphyria in Denmark (1977-1989) and Sweden (1965-1983). Patients were identified by using population-based hospitalization registries. The unique individual identification numbers of 530 patients with porphyria cutanea tarda (PCT) and 296 with acute intermittent porphyria (AIP) were linked to the nationwide cancer and death registries. Among patients with both types of porphyria, the authors found small but significantly elevated risks of all cancers combined (PCT: standardized incidence ratio (SIR) = 1.7, 95% confidence interval (CI) 1.3-2.2; AIP: SIR = 1.8, 95% CI 1.1-2.8) due to pronounced excesses of primary liver cancer (PCT: SIR = 21.2, 95% CI 8.5-43.7; AIP: SIR = 70.4, 95% CI 22.7-164.3) and moderate increases in lung cancer (PCT: SIR = 2.9, 95% CI 1.5-5.2; AIP: SIR = 2.8, 95% CI 0.3-10.2). PCT patients had a significantly increased risk of mortality from liver cirrhosis (standardized mortality ratio (SMR) = 8.4, 95% CI 3.1-18.4) or chronic obstructive pulmonary disease (SMR = 3.1, 95% CI 1.1-6.7). The increased risk of primary liver cancer and the increased risk of mortality from cirrhosis of the liver are consistent with findings from previous clinical surveys, but the new observations of excess lung cancer and chronic obstructive pulmonary disease require confirmation.

The use of artificial joint implants has risen greatly over the past years. However, few investigations of the cancer risk associated with implants have been performed. We investigated cancer risk in patients with finger and hand joint and temporo-mandibular (TMJ) joint implants. A nationwide cohort in Denmark of patients with finger and hand joint prostheses (n = 858) or TMJ implants (n = 389) was followed from January 1, 1977, to December 31, 1995, to evaluate any potential cancer risks subsequent to receiving these implants. Standardized incidence ratios (SIRs) for all cancers were 1.0 (95% CI = 0.8-1.2) for the finger and hand joint cohort and 1.1 (95% CI = 0.8-1.7) for the TMJ cohort. A significant risk for non-Hodgkin's lymphoma was found in the finger and hand joint cohort (SIR = 3.8, 95% CI = 1.5-7.8). When the finger and hand joint cohort was stratified by diagnosis of rheumatoid arthritis, the excess risk was seen only in the group with rheumatoid arthritis. This is consistent with past studies, which have found an association between rheumatoid arthritis and non-Hodgkin's lymphoma. Our results provide evidence that the cancer risk for patients with finger and hand joint prostheses and TMJ implants is similar to that for the general population.

A nationwide cohort study of hip and knee replacement patients in Denmark was undertaken to assess any carcinogenic potential of these implants. A cohort of 22,997 osteoarthritis patients who received hip replacements and of 4,771 osteoarthritis patients who received knee replacements during the period 1977 through 1989 were identified using the nationwide Danish Hospital Discharge Registry. These patients were followed for cancer occurrence through 1993, using the Danish Cancer Registry. There was no overall excess of cancer in either the hip implant cohort [standardized incidence ratio (SIR) = 0.94; 95% confidence interval (CI)= 0.91-0.98] or the knee implant cohort (SIR = 0.97; 95% CI = 0.89-1.06). The risk reduction in both groups of patients reflected for the most part reduced risks for cancers of the respiratory system and the digestive tract, particularly stomach cancer (SIR = 0.69; 95% CI = 0.50-0.81 for hip replacement patients; SIR = 0.46; 95% CI = 0.20-0.91 for knee replacement patients). Elevated risks were observed for melanoma of the skin in both groups of patients. There was no clear excess risk for lymphohematopoietic cancers or malignant neoplasms of the bone or connective tissue among implant patients in either implant group. Contrary to an earlier study in Sweden, we did not find an excess risk for kidney or prostate cancers. In summary, these nationwide results indicate no overall cancer hazard among hip and knee implant patients, but limited follow-up warrants continued surveillance of individuals undergoing these increasingly common surgical procedures.

Low or declining levels of serum cholesterol have been associated with increased mortality from cancer. We conducted a population-based cohort study of 1882 patients from one Danish county who received lipid-lowering drugs between January 1, 1991 and December 31, 1994. During the follow-up period of up to 4 years, 41 cancers were observed among users of lipid-lowering drugs, with 42.9 expected, to yield an age- and sex-standardized incidence ratio of 1.0 (95% confidence interval, 0.7-1.3). Although limited by small numbers and short follow-up period, examination by site of cancer and type of drug provided no evidence of an association. Further research is needed, however, with longer follow-up to assess more fully any potential cancer risk with these medications.

Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1. 3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer.

In the current study we linked data from the Danish Hospital Discharge Register and the Danish Cancer Registry to estimate cancer occurrence among more than 20,000 patients hospitalized at least once with rheumatoid arthritis during 1977-1987. During a follow-up interval of up to 15 years, we found increased risks of non-Hodgkin's lymphoma, Hodgkin's disease and lung cancer, while the risk of colorectal cancer was decreased. These findings were all in agreement with the results of previous studies from two other Nordic countries, which were based on a similar type of data. We also found an excess of non-melanoma skin cancer and a deficit of female breast cancer, of which only the breast cancer observation had been seen in an earlier study.