Earlier studies suggest a protective association between vitamin K antagonist (VKA) anticoagulants and the incidence of cancer. The authors examined the associations between VKA therapy and incidence of 24 site-specific cancers with a Danish population-based cohort study, using heart valve replacement as an instrumental variable. The authors enrolled 9,727 Danish residents who received a replacement heart valve between 1989 and 2006. The heart valve recipients were matched with 95,481 unexposed individuals on age and sex. The authors used the heart valve replacement instrument to estimate rate ratios associating VKA therapy with incidence of the 24 site-specific cancers using Poisson regression models. Direct associations between VKA therapy and incidence of the 24 cancers were estimated in a prescription validation subset. The instrumental variable associations were plotted according to the inverse normal of rank percentile and subjected to semi-Bayes shrinkage adjustment for multiple comparisons. The pattern of associations was consistent with a null-centered Gaussian distribution. No individual cancer site showed a substantial positive or negative association with VKA therapy in the prescription validation subset, the instrumental variable analysis, or the analysis with semi-Bayes adjustment. These results do not support the existing hypothesis that VKA therapy is associated with reduced cancer risk.
Cites: N Engl J Med. 2000 Nov 2;343(18):1337; author reply 133811183565
Cites: Cancer Epidemiol Biomarkers Prev. 2000 Sep;9(9):895-90311008906
Cites: N Engl J Med. 2000 Nov 2;343(18):1337-811183564
Cites: N Engl J Med. 2000 Nov 2;343(18):133811183567
Recent data suggest a reduced risk of malignant melanoma (MM) among atopic dermatitis (AD) patients, but an increased risk of other skin cancers (including basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]).
We examined the association between AD and skin cancers in a large cohort study in Denmark from 1977 through 2006.
Our cohort consisted of 31 330 AD patients recorded in the Danish National Patient Registry, including AD patients admitted to hospitals and specialized outpatient clinics. Linkage to the Danish Cancer Registry allowed ascertainment of skin cancers. We calculated standardized incidence ratios (SIRs) and associated 95% confidence intervals (CIs) by comparing the incidence rate of skin cancers among AD patients with that among the general Danish population.
The overall observed number of MM cases among AD patients was 12, with 21 expected, yielding a SIR of 0.59 (95% CI 0.30, 1.02), with the most pronounced protective effect among AD patients with more than 5 years of follow-up (SIR?=?0.46; 95% CI 0.19, 0.95). The corresponding SIRs for BCC and SCC were increased among AD patients (1.41 [95% CI 1.07, 1.83] and 2.48 [95% CI 1.00, 5.11], respectively).
Our findings support an inverse association between AD and MM, but an increased risk of BCC and SCC among AD patients.
We aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population.
We identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (~5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios.
We identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22-2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84-1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86-2.29).
The overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.
To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay.
Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008.
Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more. Main Exposures In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination.
Cerebral palsy, ASD, and developmental delay.
Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively.
Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.
Little is known about the risk of cancer in patients with chronic obstructive pulmonary disease (COPD), including which cancer sites are most affected. We examined the short- and long-term risk of lung and extrapulmonary cancer in a nationwide cohort of COPD patients.
We linked the Danish National Registry of Patients and the nationwide cancer registry, and examined the incidence of various cancers in 236,494 individuals with a first incident hospital contact with COPD during 1980-2008. The observed cancer incidence in this cohort was compared with the expected incidence in the general population on the basis of national age-, sex-, and site-specific incidence rates.
Median follow-up was 3.5 years. During the first year of follow-up, 9434 cancers were diagnosed in COPD patients [standardized incidence ratio (SIR) = 3.1; 95% CI 3.0 to 3.2]. The 1-year SIR was 8.5 (8.2-8.9) for lung cancer, 5.1 (5.0-5.2) for all tobacco-related cancers, and 1.9 (1.9-2.0) for other cancers. In the following years, cancer incidence was increased 1.4-fold (1.4-1.5) in COPD patients. These patients had an increased risk of developing tobacco-related cancers (SIR = 2.1; 95% CI 2.0-2.1), including cancers of the lung, larynx, tongue, oral cavity, pharynx, esophagus, stomach, liver, pancreas, cervix uteri, and urinary tract (with SIRs ranging between 1.3 and 2.8).
Patients with first-time hospital-diagnosed COPD are at considerably increased risk of developing both lung cancer and extrapulmonary cancers. Physicians should be aware of cancer in COPD patients.
Endocarditis may be a marker for bacteremia-associated occult cancer. Intensive antibiotic treatment in endocarditis is suggested to reduce long-term cancer risk. We examined these hypotheses in a nationwide cohort study.
Endocarditis patients and cancer cases were identified from the Danish National Registry of Patients and the Danish Cancer Registry during 1978-2008. We compared the incidences of various cancers among study subjects to expected incidences based on national age-, sex-, and site-specific rates.
We observed 997 cancers among 8445 endocarditis patients (median follow-up of 3.5 years), reflecting an increased standardized incidence rate (SIR) of 1.61 (95% confidence interval [CI], 1.51-1.71). Cancer risk was highly elevated during the first 3 months of follow-up (SIR=8.03; 95% CI, 6.92-9.26), partly due to a 15- to 30-fold increased risk of hematological or liver cancers. Between 3-month and 5-year follow-ups, cancer incidence remained 1.5-fold higher than expected, including 2- and 4-fold increased SIRs for colorectal and liver cancers, respectively. Beyond 5 years of observation, the overall cancer SIR was 1.21 (95% CI, 1.10-1.34). Long-term associations were weak for several cancers hypothesized to be associated with antibiotic use, including prostate, gastric, and breast cancer.
Endocarditis is a substantial clinical marker for presence of occult cancer. We found no evidence of decreased long-term cancer risk after antibiotic treatment for endocarditis.
This study aimed to validate a predefined algorithm for osteonecrosis of the jaw (ONJ) among cancer patients in the Danish National Registry of Patients and to assess the nature of clinical information recorded in medical charts of ONJ patients.
We identified potential ONJ cases recorded in 2005-2010 among cancer patients at the hospital Departments of Oral and Maxillofacial Surgery (DOMS) in three Danish regions, using a set of codes from the International Classification of Diseases, 10th revision (ICD-10). We abstracted DOMS charts of the potential cases, had the ONJ status adjudicated by an expert ONJ adjudication committee (ONJAC), and computed positive predictive values. For patients with ONJAC-confirmed ONJ, we abstracted the charts for information on ONJ clinical course. Sensitivity of the algorithm was computed using a separate sample of 101 known ONJ cases accrued in 2005-2011.
We identified 212 potential ONJ cases, of which 197 (93%) had charts available for abstraction. Eighty-three potential cases were confirmed by ONJAC, with a positive predictive value of 42% (95% confidence interval [CI] 35%-49%). DOMS charts of these 83 cases contained complete information on ONJ clinical course. Information about antiresorptive treatment was recorded for 84% of the patients. Among the 101 known ONJ cases, 74 had at least one prespecified ICD-10 code recorded in the Danish National Registry of Patients within ±90?days of the ONJ diagnosis (sensitivity 73%; 95%CI [64%-81%]).
The predefined algorithm is not adequate for monitoring ONJ in pharmacovigilance studies. Additional case-finding approaches, coupled with adjudication, are necessary to estimate ONJ incidence accurately.
Enlarged lymph nodes may be a marker of occult cancer, but accurate data on cancer risk are limited. We used population-based Danish medical registries to assess cancer risk in a cohort of patients with a first-time inpatient or outpatient hospital contact for enlarged lymph nodes during 1994-2008. Observed cancer incidences were compared with that expected in the general population. We observed 1750 cancers among 11284 patients with enlarged lymph nodes during median follow up of 4.7 years. Only 389 cases were expected. Cancer risk was 11.5% [95% confidence interval (CI): 10.9-12.1%] during the first year of follow up, corresponding to an age- and sex-standardized incidence ratio (SIR) of 21.1 (95% CI: 20.0-22.3). One-year SIRs were more than 100 times increased for head and neck cancer and lymphomas. Beyond one year of follow up, overall cancer risk remained 1.4-fold (95% CI: 1.3-1.5-fold) higher than expected, while risk of lymphoma remained six to 10 times higher. Cancer risk was also elevated among patients with other conditions known to be associated with enlarged lymph nodes, such as infections and rheumatic disorders. We conclude that enlarged lymph nodes are a marker of occult cancer and long-term risk of cancer.
Pharmacovigilance studies of cancer treatment frequently monitor infections. Predictive values of algorithms identifying disease depend on prevalence of the disease in the population under study. We therefore estimated the positive predictive value (PPV) of primary inpatient diagnosis of infection among cancer patients in the Danish National Registry of Patients (DNRP).
The algorithm to identify infections in the DNPR was based on International Classification of Diseases, 10th revision (ICD-10) codes. A physician blinded to the type of sampled infection reviewed the medical charts and assessed the presence and type of infection. Using the physician global assessment as gold standard, we computed PPVs with and without requiring agreement on infection type.
We retrieved 266 of 272 medical charts (98%). Presence of infection was confirmed in 261 patients, resulting in an overall PPV of 98% (95% confidence interval, 96%-99%). When requiring agreement on infection type, overall PPV was 77%. For skin infections, pneumonia, and sepsis, PPVs were 79%, 93% and 84%, respectively. For these infections, we additionally calculated PPVs using evidence-based criteria as the gold standard. PPV was similar for pneumonia, but lower for skin infections and sepsis.
The Danish National Registry of Patients is suitable for monitoring infections requiring hospitalization among cancer patients.
Nephrotic syndrome may be a marker of occult cancer, but population-based studies of this association are lacking. Therefore, we examined the risk and prognosis of cancer in patients with nephrotic syndrome.
We conducted this population-based cohort study in Denmark, including all individuals diagnosed with nephrotic syndrome between 1980 and 2010 without a preceding cancer history. We computed the 5-year risk of cancer accounting for competing risk by death and standardized incidence ratios (SIRs) of cancer in patients with nephrotic syndrome relative to the general population. We compared the 5-year mortality for patients with cancer after nephrotic syndrome with that for a cancer cohort without a history of nephrotic syndrome using Cox regression adjusted for age, gender, and comorbidity.
Of 4293 individuals with nephrotic syndrome, 338 developed an incident cancer during a median follow-up of 5.7 years. The 5-year risk of any cancer was 4.7% in patients with nephrotic syndrome, a 73% increased risk (SIR, 1.73; 95% confidence interval [CI], 1.55-1.92). The association was most pronounced for lung cancer, kidney cancer, lymphoma, and multiple myeloma. It was highest within 1 year of nephrotic syndrome diagnosis (SIR, 4.49; 95% CI, 3.68-5.42), but remained increased beyond 1 year (SIR, 1.34; 95% CI, 1.17-1.53). The 5-year mortality after cancer was 68.5% in patients with cancer with nephrotic syndrome and 63.4% in the cancer comparison cohort (adjusted hazard ratio, 1.20; 95% CI, 1.02-1.42).
Nephrotic syndrome is a marker of occult solid tumors and hematologic malignancies and is associated with a worsened cancer prognosis.