Jørgen H. Olsen

Prognosis of cancers associated with venous thromboembolism.

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.

A pooled analysis of magnetic fields and childhood leukaemia

Previous studies have suggested an association between exposure to 50–60 Hz magnetic fields (EMF) and childhood leukaemia. We conducted a pooled analysis based on individual records from nine studies, including the most recent ones. Studies with 24/48-hour magnetic field measurements or calculated magnetic fields were included. We specified which data analyses we planned to do and how to do them before we commenced the work. The use of individual records allowed us to use the same exposure definitions, and the large numbers of subjects enabled more precise estimation of risks at high exposure levels. For the 3203 children with leukaemia and 10 338 control children with estimated residential magnetic field exposures levels < 0.4 μT, we observed risk estimates near the no effect level, while for the 44 children with leukaemia and 62 control children with estimated residential magnetic field exposures ≥ 0.4 μT the estimated summary relative risk was 2.00 (1.27–3.13), P value = 0.002). Adjustment for potential confounding variables did not appreciably change the results. For North American subjects whose residences were in the highest wire code category, the estimated summary relative risk was 1.24 (0.82–1.87). Thus, we found no evidence in the combined data for the existence of the so-called wire-code paradox. In summary, the 99.2% of children residing in homes with exposure levels < 0.4 μT had estimates compatible with no increased risk, while the 0.8% of children with exposures ≥ 0.4 μT had a relative risk estimate of approximately 2, which is unlikely to be due to random variability. The explanation for the elevated risk is unknown, but selection bias may have accounted for some of the increase.

The Risk of a Diagnosis of Cancer after Primary Deep Venous Thrombosis or Pulmonary Embolism

BACKGROUND Several small studies have indicated an association between deep venous thrombosis or pulmonary embolism and a subsequent diagnosis of cancer, but the subject is controversial. METHODS We conducted a nationwide study of a cohort of patients with deep venous thrombosis or pulmonary embolism that was drawn from the Danish National Registry of Patients for the years 1977 through 1992. The occurrence of cancer in the cohort was determined by linkage to the Danish Cancer Registry. The expected number of cancer cases was estimated on the basis of national age-, sex-, and site-specific incidence rates. RESULTS A total of 15,348 patients with deep venous thrombosis and 11,305 patients with pulmonary embolism were identified. We observed 1737 cases of cancer in the cohort with deep venous thrombosis, as compared with 1372 expected cases (standardized incidence ratio, 1.3; 95 percent confidence interval, 1.21 to 1.33). Among the patients with pulmonary embolism, the standardized incidence ratio was 1.3, with a 95 percent confidence interval of 1.22 to 1.41. The risk was substantially elevated only during the first six months of follow-up and declined rapidly thereafter to a constant level slightly above 1.0 one year after the thrombotic event. Forty percent of the patients given a diagnosis of cancer within one year after hospitalization for thromboembolism had distant metastases at the time of the diagnosis of cancer. There were strong associations with several cancers, most pronounced for those of the pancreas, ovary, liver (primary hepatic cancer), and brain. CONCLUSIONS An aggressive search for a hidden cancer in a patient with a primary deep venous thrombosis or pulmonary embolism is not warranted.

Obesity and cancer risk : a danish record-linkage study

A cohort of 43,965 obese persons was accrued on the basis of discharge registrations from Danish hospitals, and incidence of cancer in the cohort was compared to that in the Danish population as a whole using indirect standardisation for age and period. Increased incidence was observed for cancer of the uterine corpus independently of age [114 cases, relative risk (RR) = 2.0, confidence interval 1.6-2.4], and for breast cancer in women above the age of 70 (133 cases, RR = 1.2). These findings are consistent with previous studies. In younger women, breast cancer occurred less frequently and ovarian cancer occurred more frequently than expected. Increased incidence was observed for cancers of the oesophagus (26 cases, RR = 1.9) and the liver (58 cases, RR = 1.9), probably reflecting an increased prevalence of excessive alcohol consumption in the cohort. Increased incidence was furthermore observed for cancers of the pancreas (101 cases, RR = 1.7), the prostate (96 cases, RR = 1.3) and the colon (195 cases, RR = 1.2), which may indicate the existence of risk factors which are common to obesity and to these cancers, for example, dietary habits. Kidney cancer was increased in women only. Overall, the incidence of cancer was increased by 16% in the cohort. The results were essentially unchanged by restriction to the subcohort of 8207 persons in whom obesity was the primary discharge diagnosis, and were also similar in the first year of follow-up after hospital discharge. Selection bias is, therefore, not likely to have influenced the results.

Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin

OBJECTIVE:Aspirin products are known to cause irritation and injury to the gastric mucosa. We examined the risk of hospitalization for upper gastrointestinal bleeding with use of low-dose aspirin.METHODS:This was a cohort study based on record linkage between a population-based prescription database and a hospital discharge registry in North Jutland County, Denmark, from January 1, 1991, to December 31, 1995. Incidence rates of upper gastrointestinal bleeding in 27,694 users of low-dose aspirin were compared with the incidence rates in the general population in the county.RESULTS:A total of 207 exclusive users of low-dose aspirin experienced a first episode of upper gastrointestinal bleeding with admission to the hospital during the study period. The standardized incidence rate ratio was 2.6 (95% confidence interval, 2.2–2.9), 2.3 in women and 2.8 in men. The standardized incidence rate ratio for combined use of low-dose aspirin and other nonsteroidal anti-inflammatory drugs was 5.6 (95% confidence interval, 4.4–7.0). The risk was similar among users of noncoated low-dose aspirin (standardized incidence rate ratio, 2.6; 95% confidence interval, 1.8–3.5) and coated low-dose aspirin (standardized incidence rate ratio, 2.6; 95% confidence interval, 2.2–3.0).CONCLUSIONS:Use of low-dose aspirin was associated with an increased risk of upper gastrointestinal bleeding, with still higher risks when combined with other nonsteroidal anti-inflammatory drugs. Enteric coating did not seem to reduce the risk. The findings from this observational study raise the possibility that prophylactic use of low-dose aspirin may convey an increased risk of gastrointestinal bleeding, which may offset some of its benefits.

Risk of testicular cancer in men with abnormal semen characteristics: cohort study

Abstract Objective: To explore the associations between semen characteristics and subsequent risk of testicular cancer. Design: Cohort study. Participants: 32 442 men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen during 1963-95. Main outcome measure: Standardised incidence ratios of testicular cancer compared with total population of Danish men. Results: Men in couples with fertility problems were more likely to develop testicular cancer than other men (89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9). The risk was relatively constant with increasing time between semen analysis and cancer diagnosis. Analysis according to specific semen characteristics showed that low semen concentration (standardised incidence ratio 2.3), poor motility of the spermatozoa (2.5), and high proportion of morphologically abnormal spermatozoa (3.0) were all associated with an increased risk of testicular cancer. The only other cancer group that showed increased incidence was “peritoneum and other digestive organs” (six cases; 3.7, 1.3 to 8.0). Of these, two cases were probably and two cases were possibly extragonadal germ cell tumours. Conclusions: The results point towards the existence of common aetiological factors for low semen quality and testicular cancer. Low semen quality may also be associated with increased incidence of extragonadal germ cell tumours.

Decreasing Late Mortality Among Five-Year Survivors of Cancer in Childhood and Adolescence: A Population-Based Study in the Nordic Countries

PURPOSE To assess the risk of death in patients who survive more than 5 years after diagnosis of childhood cancer and to evaluate causes of death in fatal cases. PATIENTS AND METHODS This was a population-based study in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) using data of the nationwide cancer registries and the cause-of-death registries. The study cohort included 13,711 patients who were diagnosed with cancer before the age of 20 years between 1960 and 1989 and who survived at least 5 years from diagnosis. By December 31, 1995, 1,422 patients had died, and death certificates were assessed in 1,402. Standardized mortality ratios (SMRs) for validated causes of death were calculated based on 156,046 patient-years at risk. RESULTS The overall SMR was 10.8 (95% confidence interval [CI], 10.3 to 11.5), mainly due to high excess mortality from the primary cancer. SMR for second cancer was 4.9 (95% CI, 3.9 to 5.9) and was 3.1 (95% CI, 2.8 to 3.5) for noncancer death. The pattern of causes of death varied markedly between different groups of primary cancer diagnoses and was highly dependent on time passed since diagnosis. Overall late mortality was significantly lower in patients treated during the most recent period of time, 1980 to 1989, compared with those treated from 1960 to 1979 (hazard ratio, 0.61; 95% CI, 0.54 to 0.70), and there was no increase in rates of death due to cancer treatment. CONCLUSION Long-term survivors of childhood cancer had an increased mortality rate, mainly dying from primary cancers. However, modern treatments have reduced late cancer mortality without increasing the rate of therapy-related deaths.

Cancer risk among statin users: a population-based cohort study.

Hydroxymethylglutaryl‐CoA reductase inhibitors (statins) have been linked with potential chemopreventive effects; however, the data are conflicting. We conducted a population‐based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry for the period 1989–2002. In a study population of 334,754 county residents, we compared overall and site‐specific cancer incidence among 12,251 statin users (≥2 prescriptions) with cancer incidence among nonusers and users of other lipid‐lowering drugs (n = 1,257). Statistical analyses were based on age‐standardization and Poisson regression analysis, adjusting for age, gender, calendar period and use of NSAIDs, hormone replacement therapy and cardiovascular drugs. We identified 398 cancer cases among statin users during a mean follow‐up period of 3.3 years (range 0–14 years). The age‐ and gender‐standardized incidence rates of cancer overall were 596 per 100,000 person‐years among statin users, 645 per 100,000 person‐years among nonusers and 795 per 100,000 person‐years among users of other lipid‐lowering drugs. Adjusted rate ratios for cancer overall among statin users were 0.86 (95% CI, 0.78–0.95) compared to nonusers and 0.73 (95% CI, 0.55–0.98) compared to users of other lipid‐lowering drugs. No significantly increased or decreased rate ratios were observed for any of the studied site‐specific cancers (liver, colorectum, lung, breast, prostate, female genital organs and lymphatic and haematopoietic tissue), but most estimates tended to be less than 1.0. Stratification by duration of follow‐up or number of prescriptions revealed no clear trends. In summary, individuals prescribed statins experienced a slightly reduced cancer incidence compared to population controls of nonusers and users of other lipid‐lowering drugs. Larger and longer‐term studies are needed to determine the potentially protective effect of statin use on cancer development.

Variation of Breast Cancer Risk Among BRCA1/2 Carriers

CONTEXT The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers. OBJECTIVES To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics. DESIGN, SETTING, AND PARTICIPANTS Probands were identified from a population-based, case-control study (Womens Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years. MAIN OUTCOME MEASURE Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families. RESULTS Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics. CONCLUSION There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.

Residence near high voltage facilities and risk of cancer in children.

OBJECTIVE--To investigate whether residence before and after birth near 50 Hz high voltage installations increases a childs risk of cancer and whether risk correlates with the strength of the magnetic field. DESIGN--A population based case-control study. SETTING--Denmark. SUBJECTS--1707 children under the age of 15 with leukaemia, tumour of the central nervous system, or malignant lymphoma diagnosed in 1968-86 and 4788 children taken from the central population register. MAIN OUTCOME MEASURES--Proximity before and after birth to existing or former 50-400 kV electrical transmission connections and substations and associated historical electromagnetic fields calculated on the basis of current load on line, phase ordering of line, and distance from the dwelling. RESULTS--A significant association was seen between all major types of childhood cancer combined and exposure to magnetic fields from high voltage installations of > or = 0.4 microT (odds ratio 5.6). At > or = 0.25 microT no significant association was seen (odds ratio 1.5). A possible association was also seen with cases of Hodgkins disease separately at > or = 0.1 microT. CONCLUSIONS--On the basis these results and additional descriptive data on electricity consumption and incidence of childhood cancer in Denmark since the 1940s it was concluded that the proportion of childhood cancer possibly caused by 50 Hz electromagnetic fields must be small.