Search

Aim: To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC)., Methods: We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population., Results: The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up., Conclusion: Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: In 2019, ranitidine was withdrawn due to high levels of N-nitrosodimethylamine, a probable human carcinogen. The risk of bladder and kidney cancer in ranitidine users, however, remains unclear., Methods: In a Danish nationwide cohort study, we included adults (18 years or older) without previous cancer, who between 1996 and 2008 redeemed at least two prescriptions for ranitidine and, as two separate comparison cohorts, patients with at least two prescriptions for other H2-receptor antagonists (H2-blockers), or proton pump inhibitors (PPI). Follow-up for bladder or kidney cancer started at date of the second prescription and continued to date of cancer, death, emigration, or December 31, 2018, whichever occurred first. We used propensity scores for ranitidine use to compute stabilized inverse probability of treatment (sIPT) weights and used Cox regression to compute crude and weighted HRs., Results: We identified 31,393 initiators of ranitidine, 65,384 initiating other H2-blockers, and 509,849 initiating PPI. Compared with other H2-blockers, the crude HR for bladder cancer was 1.33 [95% confidence interval (CI): 1.15-1.55], but sIPT weighting attenuated this to 1.11 (95% CI: 0.95-1.29). Compared with PPI initiators, the weighted HR was 1.24 (95% CI: 1.04-1.48). For kidney cancer, the weighted HR was 0.89 (95% CI: 0.72-1.10) compared with users of H2-blockers and 0.87 (95% CI: 0.67-1.13) compared with users of PPI., Conclusions: Our findings did not suggest a substantial increase in bladder or kidney cancer occurrence in ranitidine users., Impact: These findings are reassuring for previous ranitidine users., (©2021 American Association for Cancer Research.)

Background: We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for RCC., Methods: Using Danish health registries, we conducted a nested case-control study including 7315 RCC cases during 2000-2015. We matched each case with up to 20 controls on age and sex using risk-set sampling. We estimated odds ratios (ORs) for long-term CCB use associated with RCC using conditional logistic regression. We addressed confounding by indication by (1) adjusting for hypertension severity indicators; (2) evaluating dose-response patterns; (3) examining whether other first-line anti-hypertensives were associated with RCC; and (4) using an active comparator new user design by nesting the study in new users of CCBs or angiotensin-converting enzyme inhibitors (ACEIs)., Results: The adjusted OR for RCC associated with long-term CCB use compared to non-use was 1.76 (1.63-1.90). After we additionally adjusted for hypertension severity indicators, the OR remained elevated (OR 1.37; confidence interval [CI] 1.25, 1.49) with evidence of a dose-response pattern. Other anti-hypertensives were also associated with RCC, for example, ACEIs (OR 1.27; 95% CI = 1.16, 1.39) and thiazides (OR 1.22; 95% CI = 1.12, 1.34). In the active comparator new user design, the OR was 1.21 (95% CI = 0.95, 1.53) for use of CCBs compared with ACEIs., Conclusions: In this population, confounding by indication appeared to explain at least part of the association between RCC and dihydropyridine CCBs.

Background: Evidence suggests that among some occupational groups, there is an elevated risk of kidney cancer. This might, however, derive from a difference in smoking habits across occupational groups. The objective of this study was to determine smoking-adjusted occupational variation in the incidence of kidney cancer in Nordic males. Material and Methods: The source population for this study consisted of 7.4 million men from Denmark, Iceland, Finland, Norway, and Sweden. Data on occupation were obtained from national censuses conducted in the years 1960-1990. Data on cancer cases came from national cancer registries. A proxy for the occupation-specific smoking prevalence among all Nordic men was calculated based on the occupation-specific smoking prevalence and lung cancer incidence data for Finnish men. Smoking-adjusted standardized incidence ratio (SIR adj ) with 95% confidence intervals (95%CI) were calculated for each occupational group. Results: The highest SIR adj estimates were observed in dentists (1.32, 95%CI 1.06-1.62), journalists (1.20, 95%CI 1.00-1.42), physicians (1.19, 95%CI 1.03-1.36), public safety workers (1.18, 95%CI 1.10-1.26), administrators (1.17, 95%CI 1.13-1.22), military personnel (1.16, 95%CI 1.05-1.28), and religious workers (1.17, 95%CI 1.09-1.26). The lowest SIR adj was observed among forestry workers (0.82, 95%CI 0.76-0.88). Conclusions: Tobacco smoking plays an important role in the occupational variation in the risk of kidney cancer. The smoking-adjusted incidence of kidney cancer was increased in dentists, physicians, journalists, administrators, and public safety workers.

Adult obesity increases risks of renal cell carcinoma (RCC). This study investigated if birth weight, child body mass index (BMI) and height are associated with adult RCC. The study included 301,418 children (152,569 boys) from the Copenhagen School Health Records Register born 1930-1985 with measured weights and heights at ages 7 to 13 years. Birth weight was obtained by parental report. BMI and height were transformed to z-scores, and BMI was categorized as normal BMI or overweight. RCC was identified by linkage to the Danish Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards regression. During follow-up, 1010 individuals (680 men) were diagnosed with RCC. BMI and height were positively associated with RCC with no significant sex-differences (age 13: HR = 1.14, 95% CI 1.06-1.23 per BMI z-score, HR = 1.12, 95% CI 1.05-1.20 per height z-score). Compared to children with normal BMI at ages 7 and 13 years, children with overweight only at age 13 had higher risks of RCC (HR = 1.67, 95% CI 1.24-2.26). Compared to children with average growth in height, persistently taller-than-average children (HR = 1.06, 95% CI 1.03-1.10) and children who changed from average to above-average height (HR = 1.08, 95% CI 1.01-1.15) had increased risks of RCC. Birth weight was positively associated with RCC (HR = 1.12, 95% CI 1.05-1.20 per 500 grams). Birth weight, childhood BMI and height were positively associated with RCC risk in men and women.

Aim: To report the current incidence and estimate the future burden of renal cancer in Nordic countries until the year 2040. Methods: Most recent incidence and prevalence data for renal cancer were retrieved using the NORDCAN database (years 2011-2015). Publicly available population counts (years 2011-2015) and estimates (years 2019-2040) provided from the official statistics bureaus of the Nordic countries were used. Averaged country-specific age- and gender-stratified estimates were calculated using data from years 2011-2015 and projected into 2019 (current estimates) and for every year until 2040 (future estimates). Sensitivity analyses were made to evaluate the consequences of increases or decreases in changes in incident rates. Results: Incidence and prevalence of renal cancer increased with age and were higher among males. This study estimates incidence and prevalence in 2019 to, respectively, 910 and 5,747 for Denmark, 1,039 and 8,043 for Finland, 67 and 549 for Iceland, 914 and 6,481 for Norway, and 1,255 and 10,695 for Sweden. In all Nordic countries, the incidence and prevalence is expected to increase due to an aging population. An increasing proportion of patients will be 70 years or above. Conclusions: In Nordic countries, the burden of renal cancer will increase during the next years and a larger proportion of patients will be elderly. These demographic changes highlight the need for cancer prevention, innovation in minimally invasive approaches and focus on active surveillance strategies.

Previous studies suggest an increased cancer risk in hypertension. Patients with hypertensive nephropathy have not been studied. A national registry study was performed to assess the presence and size of this association. Clinical data and cancer diagnoses for all patients with biopsy-proven hypertensive nephropathy between 1985 and 2015 in Denmark were extracted from four national registries and compared with age- and sex-adjusted national cancer rates. The risk of cancer was twice the background population. It was raised for renal cancer (odds ratio 10.4), myeloma (13.2), skin cancer (7.9), and other/unspecified (1.8). No increase in incidence was seen until 1 year before renal biopsy and then rose rapidly. It was again normal 5 years after biopsy. Hypertensive nephropathy is associated with an increased risk of myeloma, skin, renal, and other cancers. Screening of patients with hypertensive nephropathy, in the presence of reduced renal function or significant proteinuria, may be indicated., (©2019 Wiley Periodicals, Inc.)

The purpose of this study was to evaluate the association between the use of bisphosphonates and the risk of developing renal cell carcinoma (RCC). We conducted a case-control study in Denmark, using data linked from population-based health and administrative registries. We identified all cases of RCC from 1996 to 2013 and sampled population controls in a 10:1 ratio from the underlying population free of RCC, while matching on sex, birth year and calendar time. Bisphosphonate use before RCC diagnosis, excluding the year leading up to the diagnosis, was measured using outpatient prescription dispensations. We used conditional logistic regression to compute crude and adjusted odds ratios (ORs) comparing ever vs. never bisphosphonate use in doses indicated for treatment of osteoporosis, overall and stratified by sex, with the OR estimating the incidence rate ratio. We also examined the effects by cumulative dose and specific agent. There were 2748 RCC cases and 27 480 controls. The adjusted ORs for ever vs never bisphosphonate use were 1.07 (95% confidence interval: 0.94-1.22) overall; 1.15 (1.00-1.32) for women; and 0.78 (0.54-1.12) for men. Smoking could not be directly controlled for in the analysis. We found a weak association between use of oral bisphosphonates and risk of renal cell carcinoma in females. The observed association could be due to confounding by cigarette smoking, and future studies are required to assess this association further., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objective: The aim of this study was to describe the occupational variation in the incidence of kidney cancer in the Nordic population., Methods: The population comprised of 14.9 million individuals included in censuses between 1960 and 1990. Standardized incidence ratios (SIRs) were calculated for each occupational group., Results: Significantly increased SIRs were observed in welders [1.24, 95% confidence interval (95% CI) 1.14 to 1.35], public safety workers (1.16, 95% CI 1.08 to 1.25), and seamen (1.16, 95% CI 1.07 to 1.26). Significantly decreased SIRs were found in laboratory assistants (0.76, 95% CI 0.60 to 0.94) and forestry workers (0.77, 95% CI 0.72 to 0.83)., Conclusion: A relatively small variation in the incidence of malignancies of the kidney between occupational groups was found in the cohort. There is abundant room for further progress in determining the effect of smoking in particular occupational groups.

Background: Use of statins has been suggested to protect against renal cell carcinoma (RCC); however, studies have typically been underpowered, and the results are conflicting., Objective: To determine whether the use of statins is associated with a reduced risk of RCC using high-quality registry data., Design, Setting, and Participants: We conducted a nationwide case-control study based on all histologically verified cases of RCC in Denmark between 2002 and 2012 (n=4606) matched 1:10 to cancer-free controls. Data on drug use, comorbidity, and educational level were obtained from Danish nationwide prescription, patient, and demographic registries., Outcome Measurements and Statistical Analysis: Odds ratios (ORs) and 95% confidence intervals (CIs) for RCC associated with long-term use (≥5 yr) of statins were estimated using conditional logistic regression, adjusting for potential confounders., Results and Limitations: The adjusted OR for RCC associated with long-term use of statins was 1.06 (95% CI, 0.91-1.23). Analyses stratified by duration of statin use, type of statin, and patient characteristics all yielded ORs close to unity, except for a slightly increased OR for RCC associated with long-term statin use among women (OR: 1.25; 95% CI, 0.96-1.62). The main limitation of our study was lack of information on lifestyle factors, notably obesity, which may have biased the risk estimates upward., Conclusions: Our study does not support an important chemopreventive effect of long-term statin use against RCC. The marginally increased and statistically insignificant risk estimates can readily be interpreted as a null finding, considering the lack of control for obesity and other lifestyle risk factors., Patient Summary: Previous studies have shown that the use of cholesterol-lowering drugs (statins) may protect against renal cancer. In a large study including all Danish renal cancers during an 11-yr period, we found no evidence of such an effect., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark., Material and Methods: Cancer of the kidney was defined as ICD-10 code DC 64. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013., Results: The proportion of patients diagnosed with kidney cancer over the age of 70 years has decreased from 43% in 1980 to 32% in 2012 in men and remained almost constant in women, around 50%. Incidence rates were at least five times higher in men aged 70 years more but there was no particular trend with time. In men aged less than 70 years, the incidence rates started increasing around 2000. The incidence rates were lower in women but with a similar pattern as in men. Mortality rates remained stable over time in persons aged 70 years or more while they decreased with time in younger women. Both the one- and the five-year relative survival increased steadily over time for all age groups but the survival was lower for patients aged 70 years or more than for younger patients. The prevalence increased three times from 1559 patients being alive after kidney cancer in 1980 to 4713 in 2012., Conclusion: A challenge in managing kidney cancer in the elderly is to establish interdisciplinary collaborations between different specialties, such as surgeons, clinical oncologists, and geriatricians to be able to deliver the best possible care in the future.

Aims: Despite increasing use of implantable cardioverter-defibrillators (ICDs) and reports linking selected bio-implants with cancer, the cancer risk associated with implanted ICDs remains unknown. The objective of our study was to examine cancer risk among ICD recipients., Methods and Results: We conducted a population-based cohort study using medical registries covering the entire Danish population. We identified all first-time ICD recipients during the period of 2000-11 and determined their subsequent cancer incidence. Standardized incidence ratios (SIRs) were computed by comparing observed cancer incidence in the ICD cohort with expected cancer incidence based on national incidence rates according to age, sex, and year of diagnosis. A total of 6723 ICD recipients were followed for up to 12 years (median 2.8 years) and contributed a total of 23 254 person-years of follow-up. Compared with the general population, ICD recipients had a slightly elevated overall risk of cancer [SIR = 1.1 (95% confidence interval (CI): 1.0-1.2)]. This was driven by the cancer risk among patients with ischaemic heart disease (IHD) [SIR = 1.1 (95% CI: 1.0-1.3)], which, as expected, was particularly elevated for tobacco-related cancers [SIR = 1.4 (95% CI: 1.2-1.6)]. Importantly, ICD recipients without IHD were not at increased cancer risk [SIR = 1.0 (95% CI: 0.8-1.3)]., Conclusion: This nationwide population-based cohort study with up to 12-year follow-up did not indicate a causal relation between ICD implantation and cancer. However, more follow-up data are needed to entirely rule out risks for individual cancer types., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients. In the incidental group, the size (p<0.05), pathological stage (p<0.001), Fuhrman grading (p<0.0001) and Leibovich score (p<0.0001) were lower than in those causing symptoms. Significantly less in the incidental group had metastasis at follow-up (p<0.0001). Incidentally discovered RCC constitute a major part of kidney tumors. They have a more favorable prognosis than symptomatic tumors and seem to be discovered in an earlier phase. Needle core biopsy is an accurate technique for distinguishing between malignant and benign tumors and is recommendable for smaller incidental tumors. Screening may help detect RCC at an earlier stage., (© 2014 APMIS. Published by John Wiley & Sons Ltd.)

Background: Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma., Methods: We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided., Results: Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased., Conclusions: Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.

Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry-based case-control study involving 690 cases of Wilms tumor aged 0-14 years, occurring in Denmark, Finland, Norway or Sweden during 1985-2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population-based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50-2.59) but not for boys (1.04, 0.78-1.38); overall, the OR was 1.43 (1.17-1.74). Among girls, risk increased by 28% (15-42%) per 500 g increase in birth weight. Large-for-gestational age girls also had a higher risk (2.48, 1.51-4.05), whereas no effect was seen for boys (1.12, 0.60-2.07). An association was seen with Apgar score at 5 min < 7 for both sexes combined (5.13, 2.55-10.3). ORs close to unity were seen for parental age and birth order. In our large-scale, registry-based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor., (Copyright © 2010 UICC.)

Background: Previous studies have shown systematic differences between the Nordic Countries in population-based relative survival following a kidney or urinary bladder cancer diagnosis. Comparison of bladder cancer over time and between Nordic registries is complicated by variable coding practices with respect to the inclusion of in situ cases with invasive tumours., Material and Methods: Five-year relative survival of patients with urinary cancer diagnosed in the Nordic countries 1964-2003 and followed up for death through 2006 was studied and contrasted with developments in incidence and mortality., Results: The survival following bladder cancer was higher than for kidney cancer and highest for men. Survival increased over the years in all countries, more for kidney cancer than bladder cancer. For Danish kidney cancer patients, the rate of increase over all the years has been lower than in the other countries, especially among women, resulting in a survival in Denmark some 10-20% points lower than elsewhere in 1999-2003. Danish bladder cancer patient survival was in the last period 4% points lower among men and 10% points lower among women than in the other Nordic countries. The differences were mainly found in the first year following diagnosis, where a higher excess mortality in Denmark was observed. Survival decreased with higher age at diagnosis., Conclusion: The increasing 5-year relative survival in all the Nordic countries for both kidney and bladder cancer are promising, but for kidney cancer a higher percentage detected coincidentally during an imaging investigation for other diseases could play a role. Denmark had the lowest survival, despite their known practice of including benign conditions with invasive bladder cancers. The lower Danish survival after kidney and bladder cancer in the first year after diagnosis could be due to later diagnosis on average, a higher co-morbidity from smoking-related diseases, and perhaps, less adequate cancer treatment and management in Denmark.

Objectives: To determine changes in the population-based incidence rates, degree of histologic verification, and morphologic distribution of tumors of the kidney, pelvis, and ureter and bladder in both sexes for the duration of 60 years in Denmark., Methods: Age-standardized incidence rates in 5-year age and calendar intervals, histologic verification and morphologic distribution were derived from reports to the Danish Cancer Registry., Results: The incidence of kidney tumors increased by 78% among men and 32% among women during the study period; the incidence of pelvis and ureter tumors increased by 1070% and 2785%, respectively, and those of bladder tumors increased by 325% and 195%, respectively. The incidence of Wilms tumor was stable; the incidence of other kidney tumors leveled out during the last 30 years of the period and those of other 2 groups during the last 20 years. The frequency of histologic verification was stable for pelvis and ureter cancers and Wilms tumor and increased for kidney and bladder tumors. Most of the kidney tumors were of epithelial origin and most others were of urothelial origin., Conclusions: The overall incidences of all tumors increased in both sexes during the 60-year period. Some of the increase could be due to improved diagnosis. The recent decline in rates might be due to reduced exposure to risk factors., (Copyright 2010. Published by Elsevier Inc.)

Purpose: Comorbid disease in patients with renal cancer may affect renal cancer prognosis. We estimated the risk of 1 and 5-year mortality in patients with renal cancer in northern Denmark by comorbidity status., Materials and Methods: We performed a cohort study tracking mortality in all patients with an incident diagnosis of renal cancer between 1995 and 2006 in a population of 1.6 million residents in northern Denmark. Using hospital discharge data before cancer diagnosis we calculated Charlson comorbidity index scores (0, 1-2 or 3+) in patients with renal cancer as well as absolute survival and relative mortality estimates according to comorbidity level., Results: We identified 2,315 patients with renal cancer, of whom 950 (41%) had comorbidity. The prevalence of comorbidity tended to increase during the study period with the rate in patients with a score of 3+ increasing from 9% to 13%. The 5-year relative mortality rate was lower in patients with a positive Charlson index score with mortality almost twice as high in those with a score of 3+ and 1.2-fold higher in those with a score of 1-2 compared to mortality in those with no comorbidity. Generally similar patterns were observed for 1-year relative mortality., Conclusions: Comorbidity is common in patients with renal cancer and it is a negative prognostic factor.

We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from cancers of the kidney and urinary bladder diagnosed in Denmark during 1994-2003 with follow-up through 2006 using information from nationwide registers. The analyses were based on data on 2941 patients with kidney cancer and 9471 patients with urinary bladder cancer in a cohort of 3.22 million people born between 1925 and 1973 and aged >or=30 years. Our results indicate that lower socioeconomic position is associated with higher incidences of cancers at both sites in both sexes, whether socioeconomic position is measured as educational level, disposable income, affiliation to the work market, housing tenure or size of dwelling. We also found a moderate pattern of better survival from cancers at both sites in the most advantaged groups, most clearly reflected by the level of education, disposable income and affiliation to the work market.

We studied 335,682 county residents, of whom 113,298 had been prescribed antihypertensive treatment (AHT), in the period 1989-2002 in North Jutland County, Denmark to examine the relation between different AHTs and the risk of renal cell carcinoma (RCC). An internal comparison was performed among the different classes of AHT users with users of beta blockers as the reference, in order to address potential confounding and bias. The average follow-up was 10 years (range 0-13). Use of any AHT was associated with RCC (relative rate (RR)=1.6, 95% confidence interval (CI) 1.3-1.9) compared with nonusers in the general population. Specific classes of AHTs were nonsignificantly associated with RCC, but compared with users of beta blockers, the numbers observed were close to expectation. Analyses by duration of follow-up and number of prescriptions revealed no clear trends for any antihypertensive agent and after 5-years of follow-up, the RRs for all classes of AHT decreased. The elevated RRs for RCC among users of AHTs compared with the general population are unlikely to be causal, but rather reflect confounding due to failure to control for pre-existing hypertension, and protopathic bias, due to the presence of hypertension as an early sign of kidney disease.

Mechanistic data must be incorporated into the assessment of the human risks of chemical carcinogens, for trichloroethylene in particular. The total weight of evidence compiled from data on the genotoxicity of trichloroethylene indicates that systemic mutagenic activity is not expressed in vivo. New epidemiologic data on trichloroethylene generated in Denmark showed a steady decline of occupational exposure to trichloroethylene since 1947, but with occasions of high exposures before 1980. Earlier exposures were related to a slight increase in risk of non-Hodgkin's lymphoma, renal carcinoma, and esophageal carcinoma. Such confounders as coexposure to other industrial solvents (non-Hodgkin's lymphoma) and alcohol drinking (esophageal cancer) must be discussed. In Germany, a new consecutive case-control study on kidney cancer confirmed that the risk of renal cell cancer is significantly elevated in persons reporting long-term (several years) exposure to trichloroethylene. The results of all these studies indicate that low exposure (not higher than the current Occupational Exposure Limits) is not associated with increased risk of malignancy. In the kidney, trichloroethylene can act as a complete carcinogen at the stages of both tumor induction and tumor promotion/progresssion in a in a dose-dependent manner. Different types of kidney cancer can be triggered by different genes. Clear-cell renal carcinoma, preferentially induced by trichloroethylene, is linked with the homozygous inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. In highly exposed subjects, the local genotoxic effect of trichloroethylene results from bioactivation pathways leading to renal VHL gene damage and renal cell carcinomas. The view that renal cell cancer development after long-term (several years) and high (with prenarcotic episodes) occupational exposure to trichloroethylene is due to chronic damage of the proximal tubule of the kidney as a key step argues for the existence of a practical threshold. Prolonged and unusually high-dose exposure to trichloroethylene is deemed a strong risk factor for the development of renal cell cancer. The findings of experimental, mechanistic, and epidemiologic studies lead to the conclusion that trichloroethylene can be considered a human carcinogen for which a practical threshold appears likely and below which no relevant carcinogenic effect is to be expected.

Background: The aim of this study was to compare the frequency of imprinting diseases in children born after IVF with the incidence in naturally conceived children., Methods: All singleton children born in Denmark from January 1, 1995 through December 31, 2001 were stratified into children born without and after IVF, and were followed from birth until the end of 2002 in the National Register of Patients and the Central Register of Psychiatric Diseases, which include all discharge diagnoses from somatic and psychiatric hospitals/clinics, respectively. Included in the study were malignancies, mental, behavioural and neurological diseases, congenital syndromes, and developmental disturbances. Only diagnosis codes potentially relevant for imprinting diseases were included., Results: During the 7-year study period, 442,349 singleton non-IVF and 6052 IVF children were born. Mean follow-up time was 4.5 and 4.1 years for the two groups, respectively, corresponding to 2 million and 25 000 follow-up years. In the IVF/non-IVF cohort, we detected 0/72 children with cancer, 47/3766 with mental diseases, 72/3654 neurological diseases, 4/287 congenital syndromes and 96/6727 developmental disturbances, in a total of 219/14,506 clinical outcomes. The number of children with specific imprinting diseases in the non-IVF group was 54: 44 kidney cancers, five retinoblastoma, three Prader-Willi syndrome and two Russel-Silver syndrome. Anticipating the same occurrence in IVF children, the total expected number was calculated to be 0.74. The observed number in the IVF group was 0. We found a significantly increased risk of cerebral palsy in the IVF group, with a rate ratio (RR) (IVF:non-IVF) of 1.8 [95% confidence interval (CI) 1.2-2.8; P < 0.01], and of sleeping disturbances, with an RR 2.0 (95% CI 1.2-3.3). The incidence rate of childhood cancers, mental diseases, congenital syndromes and developmental disturbances was equal in the two groups., Conclusions: We found no indication of an increased risk of imprinting diseases after IVF, but an 80% increased risk of cerebral palsy. We observed equal frequencies of childhood cancers, mental diseases, congenital syndromes and developmental disturbances in the two groups. Danish register data do not support reports of an increased risk of imprinting diseases after IVF.

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.)

Until the introduction of self-service around 1970, service station workers in the Nordic countries were exposed to gasoline vapors. Based on measurements reported in the literature, the 8-hour time-weighted average benzene exposure was estimated to be in the range of 0.5-1 mg/m3. We studied the cancer incidence in a cohort of 19,000 service station workers from Denmark, Norway, Sweden, and Finland. They were identified from the 1970 censuses and followed through 20 years, where 1,300 incident cancers were observed. National incidence rates were used for comparison. The incidence was not increased for leukemia (observed = 28, standardized incidence ratio (SIR) = 0.9, 95% confidence interval (CI) 0.6-1.3) not for acute myeloid leukemia (observed = 13, SIR = 1.3, 95% CI 0.7-2.1). The incidence was slightly elevated for kidney cancer observed = 57, SIR = 1.3, 95% CI 1.0-1.7) and for pharyngeal, laryngeal, and lung cancer. A 3.5-fold risk of nasal cancer was found (observed = 12, SIR = 3.5, 95% CI 1.8-6.1). This cohort exposed to gasoline vapors with benzene levels estimated to be 0.5-1 mg/m3 showed no excess risk of leukemia or acute myeloid leukemia, a 30% elevated risk of kidney cancer, and a previously unnoticed risk of nasal cancer.

Objectives: To study the cancer incidence in printing workers in Denmark., Methods: The cohort of 15,534 men and 3593 women working in the printing industry in 1970 were followed up for death, emigrations, and incident cancer cases until the end of 1987. Their cancer incidence was compared with that of all economically active people in Denmark. The smoking and drinking habits reported by members of the printing trade unions at a survey in 1972 were compared with habits reported by members of other trade unions., Results: Lung, bladder, renal pelvis, and primary liver cancers were in excess among the printing workers. The excess risks of lung cancer among the factory workers in newspaper and magazine production, of bladder cancer in typographers in printing establishments, of renal pelvis cancer in typographers and lithographers, and of primary liver cancer among lithographers and bookbinders exceeded those expected based on the reported smoking and drinking habits., Conclusion: Our results indicate, in line with a previous study from Manchester, that work with rotary letterpress printing was associated with an increased risk of lung cancer. The inconsistent results from studies on bladder cancer in printing workers may point to a risk confined to a certain subgroup. The sixfold risk of primary liver cancer in Danish lithographers warrants studies in other countries.

Objectives: Previous studies have shown an excess risk of primary liver cancer among women working in laundries and dry-cleaning shops in Denmark at the time of the census in 1970. During the period 1970-1987, 14 cases of primary liver cancer were observed (standardized mortality ratio 2.7, 95% confidence interval 1.5-4.5). A nested case-referent study was undertaken in order to classify laundry workers and dry-cleaning workers separately. According to hints in the literature, renal-cell carcinomas were also included in this analysis., Methods: Original census forms from 1970 were retrieved from the Danish National Record Office for the 17 cases with primary liver cancer and the 16 cases with renal-cell carcinoma and five matched referents per case., Results: All of the 17 patients with primary liver cancer worked in laundries in 1970, whereas only 74% of the referents worked in laundries. Neither was the risk of renal-cell carcinoma associated with dry-cleaning work (relative risk 0.7, 95% CI 0.2-2.6)., Conclusions: The excess risk of primary liver cancer observed for women working in laundries and dry-cleaning shops in Denmark is not likely to be explained by exposure to dry-cleaning solvents. Excessive alcohol consumption is not a likely explanation either, and the excess risk therefore remains unexplained.

The relationships between reproductive factors, exogenous hormones and renal-cell cancer were examined in an international, multicenter, population-based, case-control study undertaken in 1989-1991. Data from 5 centers situated in Australia, Denmark, Germany, Sweden and the United States included for analysis 608 women with renal-cell cancer and 766 female controls. A significant trend in risk (p = 0.002) was associated with number of births, with an 80% excess risk for 6 or more births [RR = 1.8, 95% confidence interval (CI) = 1.1 to 2.9] compared with one birth. A decreasing risk was seen for increasing age at first birth, although this was confounded by body-mass index and number of births. A suggestive reduction of risk was also seen for increasing age at menarche. Age at menopause was unrelated to risk of renal-cell cancer. An increased risk was observed for women having had both a hysterectomy and an oophorectomy. Use of oral contraceptives in non-smoking women reduced the risk of renal-cell cancer (RR = 0.5, 95% CI = 0.4 to 0.8); this reduction increased with longer duration of use. No association was observed for estrogen replacement therapy. Our results indicate that certain hormonal and reproductive variables may be related to risk of renal-cell cancer and deserve further investigation, both epidemiologically and experimentally.

Patients with chronic lymphocytic leukemia (CLL) are known to to have an increased incidence of secondary cancers. We investigated the occurrence of secondary cancers in 7391 patients with CLL diagnosed between 1955 and 1988. The observed number of cancer cases was compared with the expected number of cancers calculated from national cancer incidence rates. The overall risk of cancer was significantly increased among persons with CLL. The standardized incidence ratios (ratio between the observed and the expected numbers) were 2.0 for men and 1.2 for women. Increased risks were found for cancer of the lung and prostate in men (RR = 2.0 and 1.5 respectively), renal parenchyma in both sexes (RR = 2.8 for men, RR = 3.6 for women) non-melanoma skin cancer in both sexes (RR = 4.7 for men, RR = 2.4 for women) and sarcomas (RR = 3.3 for men, RR = 2.8 for women). Although an increased risk of cancer is to be expected solely because individuals with CLL are being physically examined frequently, it appears that the risk is significantly increased for a number of cancer sites in persons with CLL.

Background: Several recent studies of risk factors for renal cell carcinoma have indicated that use of diuretics may increase risk of this cancer. It has also been suggested that use of weak analgesics, which are known to increase risk of cancer of the renal pelvis and ureter, may also be associated with an increased risk of renal cell carcinoma--the most frequent type of kidney cancer., Methods: A population-based case-control study was undertaken to investigate the role of diuretics, other anti-hypertensive drugs, analgesics, and medical history in the aetiology of renal cell carcinoma. The study base was the total Danish population, and 368 histologically verified cases and 396 sex- and age-matched controls who were interviewed from February 1989 to May 1992., Results: Response rates were 76% among cases and 79% among controls. We found no general increase in risk among users of diuretics or analgesics, although women taking loop diuretics and heavy users of acetyl salicylic acid had slightly increased risks. The use of nondiuretic anti-hypertensive medications was associated with decreased risk in women. We found non-significantly increased risks for history of hypertension and other cardiovascular disorders. We also observed elevated risks for urological disorders in both sexes which may be a result of recall bias., Conclusion: This study provides only limited support for the suggested association between risk of renal cell carcinoma and use of diuretics and analgesics. The coexistence of renal cell carcinoma and cardiovascular diseases could be caused by risk factors that are common to these conditions.

Objectives: Risk factors for renal-cell carcinoma, the most frequent type of kidney cancer, remains enigmatic. Time trends in incidence and changes in the regional distribution of this cancer are suggestive of environmental risk factors. This study reports on occupational risk factors for renal-cell carcinoma in Denmark., Methods: In a population-based study, 365 persons with histologically verified renal-cell carcinoma and 396 referents were interviewed. Information was collected on occupation, education, and occupational exposure to a number of suspected substances, including hydrocarbons, asbestos, and radiation., Results: Risk of renal-cell carcinoma was found to be associated with employment as a truck driver, exposure to gasoline, other hydrocarbons, and insecticides and herbicides. The risk of renal-cell carcinoma was higher in the lower socioeconomic strata for both the men and the women. Nonsignificantly elevated risks were observed for employment in oil refineries, gasoline stations, and the iron and steel industry. No association was found for exposure to radiation or for employment in industries such as leather manufacturing and health care, which have previously been linked to an increased risk of renal-cell carcinoma., Conclusions: The risk of renal-cell carcinoma is increased in lower socioeconomic strata, and previously identified or suspected risk factors do not explain the excess in risk. This study adds additional support to the hypothesis of a link between renal-cell carcinoma and hydrocarbons and also demonstrates the need for further studies on occupational risk factors for renal-cell carcinoma.

Risk factors for renal cell carcinoma were examined in a population based case-control study in Denmark. A total of 368 cases and 396 age- and gender-matched controls were interviewed in their homes. Increased risk was associated with low socioeconomic status. For men, an increasing risk with decreasing socioeconomic status was seen (odds ratio [OR] = 2.2, 95 percent confidence interval [CI] = 1.0-4.6 for men in the lowest socioeconomic stratum cf the highest). For women, the risk was lower in the highest socioeconomic stratum compared with the rest (OR = 2.4, CI = 0.9-5.9 for the lowest strata cf the highest). Cigarette smoking was a risk factor in men with an OR = 2.3 (CI = 1.1-5.1) for cigarette smokers with a total consumption of more than 40 pack-years compared with nonsmokers. Family history of kidney cancer was associated with an increased risk in both genders (for men, OR = 4.1, CI = 1.1-14.9; for women, OR = 4.8, CI = 1.0-23). Observations were inconsistent regarding coffee and alcohol consumption, and we found no association with tea drinking. The association with socioeconomic status remained after adjustment for other factors.

A population-based case-control study of risk factors for renal-cell carcinoma was conducted in Denmark from 1989 to 1992. A total of 368 histologically verified cases and 396 controls were included. Information on weight, height, physical activity and reproductive factors were collected in a structured interview, along with information on other suspected risk factors. A significant increase in risk was seen for obese women but not obese men. Although there was no clear gradient, the risk was highest among women with a relative weight in the upper 5% (OR 6.1; 95% CI, 2.3 to 16.1). The increased risk was most evident for high relative weight in ages 30 to 50. No association was observed for height or physical activity. Use of amphetamines was associated with increased risk but, because of the close link with obesity, we were unable to provide evidence that amphetamines are an independent risk factor. We found some evidence for an association with reproductive variables, including decreased risk for women with late menarche and first pregnancy and birth. We observed no association with number of pregnancies or age at menopause, or use of estrogen-containing medication.

Temporal trends in the incidence of cancer of the renal parenchyma, renal pelvis, ureter, bladder, urethra and Wilm's tumor in the period 1943-88 were described. Log-linear Poisson models were used to estimate the changes over time and the geographical variations. We have found a steep increase in the incidence of pelvis and ureter cancer; and to some extent also for bladder cancer in men. The incidence of cancer of the renal parenchyma has increased more moderately while the rates of Wilm's tumor have been virtually stable throughout the period. These findings suggest that tumors in the urinary system differ with respect to risk factors and should be grouped by their histological origin as well as topographical site.

The 15,160 males and females diagnosed with kidney cancer in Denmark in the period 1943-87, and eligible for inclusion were covered in the analysis. Crude and relative five-year survival from this cancer has improved with calendar time, especially for men. For patients diagnosed in 1943-47, the relative five-year survival was 18% for men and 29% for women; for those diagnosed in 1983-87, it had improved to 35 and 36%, respectively. Patients with localized tumours at the time of diagnosis had a more favourable prognosis than those with disseminated disease, with a five-year survival of 51% for men and 53% for women; people of each sex with metastatic disease had a five-year survival of only 3%. Treatment of kidney cancer throughout the period was surgical removal of the kidney and lymph nodes. The moderate improvement in survival seen with calendar time may be due to better, more efficient surgical techniques. The 32,701 patients diagnosed with cancer of the urinary bladder in 1943-87 and included in the study experienced a marked improvement in crude five-year survival: for both men and women, from 24% for patients diagnosed in 1943-47 to 47% for those diagnosed in 1983-87. Patients whose tumours were localized at the time of diagnosis in 1978-87 had a more favourable prognosis, with survival after 10 years of 36% (men) and 43% (women), than patients with metastatic disease with 10-year survival of less than 1% (men and women). The treatment of bladder tumours underwent a number of changes during the study period. The improvement in survival with calendar time may be due to more efficient treatment, although registration artefacts cannot be excluded.

In Denmark, total rather than subtotal hysterectomy has been recommended as treatment for benign conditions of the uterine corpus, primarily due to the risk of cervical cancer in the residual stump. Due to possible benefits during and after surgery, it has recently been argued that total hysterectomy for benign conditions could be substituted by subtotal hysterectomy, particularly since cancers of the cervix are declining as a consequence of screening. Cancer risk following supravaginal uterine amputation among 1104 Danish women undergoing operations during 1978-1988 was studied using record linkage techniques with the Danish Cancer Registry. No overall cancer risk, nor an overall increased risk of cancers coded as cervical, was observed. However, a 3.3 to 5.0-fold increased risk for cervical cancer was observed among women whose operations occurred at 50 years of age or older, possibly reflecting an increased risk of cancer in the endocervical area or in remaining uterine tissue. This observation, together with the difficulties in treating a cervical cancer of the stump when it does occur, should be taken into account before a change in surgical procedures from total to subtotal hysterectomies is recommended.

A review based on data from the Cancer Register reveals that the age-standardized incidence rate of tumours of the renal pelvis and ureter in Denmark has increased more than ten-fold where both men and women are concerned during the 40 year period from 1943 to 1982. A random control sample suggest underreporting of pelvic tumours of 8% and it is known from previous investigations that 95-98% of all known cases of tumour are registered in the Cancer Register. These circumstances suggest a greater increase in the incidence than that registered in the present article. Where tumours of the renal pelvis in men are concerned, however, the development was reversed in the middle of the nineteen seventies with a decrease in the incidence continuing to the conclusion of the period of this review in 1986. The decrease in tumours of the renal pelvis in men is observed particularly in the capital and in rural districts. A possible cause of this decrease is reduction of tobacco consumption in men. The incidence of tumours of the ureter in men is still increasing but the account is based on few observations. Possible reasons for the uninterrupted increase in incidence of tumours of the renal pelvis and ureter in women continuing until the conclusion of the period of registration is the increasing tobacco consumption which has been observed in women and consumption of phenacetin before this preparation was deleted from the drug register in Denmark.

Studies on the possible association between exposures of parents at the time off conception and cancer in their offspring have provided no clear answer. In this large, population-based, record-linkage study, 1747 childhood cancer cases were identified in the Danish Cancer Registry and matched with 8630 population controls. Specific information on the employment held by each parent at the time of conception and during early pregnancy was obtained through record linkages. The most recent job titles of the parents were also supplied. Significantly increased risks for renal cancer (mainly Wilms' tumour) and for osteogenic and soft tissue sarcomas were observed in children in association with mothers' employment in medical and dental care, based on 15 observations and odds ratios (OR) of 2.5-4.0. The risk for cancers at all sites was significantly elevated in children of female nurses (OR = 1.4; n = 75) and of male and female physicians, dentists, dental assistants, veterinarians and pharmacists combined (OR = 1.4; n = 53). Handling of drugs, exposure to anaesthetics and infections during pregnancy are suggested to be potential risk factors. Significantly increased risks were also observed for children of fathers employed in the manufacture of iron and metal structures (OR = 2.2; n = 16), in machine repair workshops (OR = 2.8; n = 6), as machinists (OR = 1.6; n = 47) and as smiths (OR = 1.5; n = 28). The suggestion in earlier studies that exposures to hydrocarbons and lead are risk factors for childhood cancer could not be supported by our analysis. Overall, few associations were observed; it was therefore concluded that parental occupation is not likely to be a major risk factor for childhood cancer.

During the past 45 years, the number of new cases of parenchymatous renal cancer have increased from approximately 230 to over 500 per annum. The incidence of renal cancer increased until the middle of the nineteen seventies, after which it stagnated. Parenchymatous renal cancer is nearly twice as frequent in men. During the entire period, Wilms' tumour and sarcoma have been very rare with only few new cases every year.