Use of Systemic Corticosteroids and Risk of Esophageal Cancer
Bibliographic record
Abstract
To the Editor: The incidence of adenocarcinoma of the esophagus has increased steeply in several industrialized countries in the last few decades, whereas the incidence of squamous cell carcinoma has remained almost unchanged. Overall, esophageal cancer has become the eighth most common type of cancer worldwide in the 1990s. 1 The reasons for this increase are largely unknown, although elevated risk has been demonstrated with gastroesophageal reflux, obesity, and drugs relaxing the lower esophageal sphincter. 2,3 Corticosteroids are increasingly used in the treatment of several chronic diseases, eg, rheumatoid arthritis, polymyalgia rheumatica, asthma, chronic obstructive lung disease, and inflammatory bowel diseases. As both obesity and esophageal candidiasis 4 are known side effects of corticosteroids, the increased risk of esophageal cancer associated with these conditions might partly be a result of the use of corticosteroids. We examined the incidence of esophageal cancer in a large cohort of corticosteroid users in Denmark. We used the population-based Pharmaco-Epidemiological Prescription Database in North Jutland County, Denmark (population 490,000) to identify 233,728 corticosteroid prescriptions for tablets and injections filled for 59,685 individuals between January 1, 1989 and December 31, 1996. All pharmacies in the county are equipped with a computerized accounting system from which data are transferred both to the National Health Service (to secure reimbursement of the costs associated with the purchase of corticosteroids and other drugs) and to the Prescription Database. Through linkage to the Danish Cancer Registry, the cohort was followed for the occurrence of esophageal cancer from the date of the first prescription for corticosteroids until the date of death or until December 31, 1996. The number of incident cases with esophageal cancer observed among cohort members was compared with the number expected on the basis of age-, sex-, county-, and calendar year-specific cancer incidence rates. The standardized incidence ratio was calculated as the ratio of the observed to the expected number of cases by years of follow-up and the total number of prescriptions issued by the patient. The cohort of corticosteroid users accrued 245,775 person-years of follow-up, with a mean follow-up period of 3.7 years. We found an increased risk of esophageal cancer in users of corticosteroids, on the basis of 36 observed cases compared with 18.8 expected cases, yielding a standardized incidence ratio of 1.92 (95% confidence interval = 1.34–2.65). The risk was increased in all latency periods (Table 1).Table 1: Observed and Expected Numbers and Standardized Incidence Ratio (SIR) of Esophageal Cancer in 59,685 Users of Systemic Corticosteroids, 1989–1996, North Jutland County, DenmarkOur study indicates a positive association between use of corticosteroids and esophageal cancer. Confounding from, eg, alcohol, smoking, body weight, and concomitant use of other sphincter-relaxing drugs 3,5 may play a role, but in the present study we could not determine the impact of these factors. The association between use of corticosteroids and esophageal cancer deserves further explanation. Henrik Toft Sørensen Lene Mellemkjaer Søren Friis Jørgen H. Olsen
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".