Using cancer registry data: agreement in cause-of-death data between the Ontario Cancer Registry and a longitudinal study of breast cancer patients.

Data from the Ontario Cancer Registry (OCR) were compared with data from a multi-centred prospective cohort of 1655 node-negative breast cancer patients with intensive clinical follow-up. Agreement in cause of death was evaluated using kappa statistics. The accuracy of OCR classification was evaluated against the Mount Sinai Hospital (MSH) study oncologist's interpretation of intensely followed, cohort-collected data as the reference standard. The two sources showed a high level of agreement (kappa statistic [kappa] = 0.88; 95% confidence interval [CI]: 0.86, 0.90) in vital status and cause of death. Among those cases where both sources reported a death, the OCR had a sensitivity of 95% (95% CI: 90.5, 98.8) and a specificity of 88% (95% CI: 79.6, 92.4). The OCR is a valuable tool for epidemiologic studies of breast cancer to acquire adequate and easily attainable cause-of-death information.

A study of smoking, p53 tumor suppressor gene alterations and non-small cell lung cancer.

PURPOSE: The purpose of this study was to investigate the relationship between smoking and p53 tumor suppressor gene alterations, and their association with clinicopathologic features and prognosis in non-small cell lung cancer (NSCLC). METHODS: For 111 of 119 stage I-III NSCLC patients that had been followed prospectively, tumor p53 protein accumulation was measured immunohistochemically (IHC). Staining was evaluated as a score (p53IHCS) combining intensity and percent distribution. RESULTS: Forty-eight of 111 (43%) tumors had p53IHCS > 1. p53 IHC was associated with increasing tumor size (T) (p = 0.035), nodal status (N) (p = 0.091), stage (p = 0.054), and histology: squamous cell carcinoma (70%) and adenocarcinoma (27%) (p = 0.0002). In logistic regression analysis, p53 IHC was associated with squamous cell histology versus other histotypes [adjusted odds ratio (OR)5.90, 95% confidence interval (CI) 2.34-14.90]. p53 IHC was not associated with smoking variables. In multivariate proportional hazards analysis, p53IHCS and pack-years smoked (PY), both as continuous variables, were negative prognostic factors. The adjusted hazard ratios (HR) for the survival outcome recurrence for p53IHCS and PY were 1.20 (95% CI 1.02-1.40) and 1.03 (95% CI 1.01-1.04), and for death due to recurrent disease (DRD) were 1.35 (95% CI 1.11-1.64) and 1.03 (95% CI 1.01-1.04), respectively. Comparing the 75th percentile to the baseline 0, the adjusted HR for p53IHCS (5 vs. 0) was 4.5 and for PY (55 vs. 0) was 5.1 for the outcome DRD. Both variables demonstrated a dose-response relationship with survival. CONCLUSIONS: PY and p53IHCS are significant, independent and important predictors of recurrence and DRD in stage I-III NSCLC.

Meta-analyses of p53 tumor suppressor gene alterations and clinicopathological features in resected lung cancers.

p53 alterations are the most common genetic lesions observed in lung cancers. Because of the limited size of individual studies, the distributions of p53 alterations by clinicopathological features have not been well characterized. Here, we present meta-analyses describing the occurrence of p53 alterations by patient/tumor characteristics in resected lung cancer. The association between p53 alterations (gene and/or protein) and a variety of variables were evaluated by calculating pooled odds ratios (ORs) and confidence intervals (CIs). p53 alterations were detected in 46.8% of 4684 non-small cell lung cancers. p53 alterations occurred more frequently in the more strongly smoking-associated histotypes: squamous cell (51.2%) and large cell (53.7%) carcinomas versus adenocarcinomas [38.8%; OR (squamous versus adenocarcinoma) = 1.81, 95% CI = 1.55-2.11]. p53 alterations were found to be associated with T1-4, N0-3, stage I-III, differentiation, and sex: OR (T3 versus T1) = 1.62 (95% CI = 0.99-2.65), OR (N1-3 versus N0) = 1.65 (95% CI = 1.27-2.15), OR (stage III versus stage I) = 1.98 (95% CI = 1.35-2.89), OR (poorly and moderately versus well-differentiated) = 3.04 (95% CI = 1.56-5.94), and OR (male versus female) = 1.39 (95% CI = 1.10-1.75). No strong associations between p53 and ras or aneuploidy were observed. Lung cancer studies of p53 and smoking need to consider the effect of histotype, and prognostic studies of p53 should adjust for the effects of T and N or stage and histotype. The apparent association between p53 and sex may be confounded by histotype and must be evaluated by multivariate studies.

Methodological issues in assessing reproducibility--a comparative study of various indices of reproducibility applied to repeat ELISA serologic tests for Lyme disease.

This study applies and evaluates a variety of different measures of reproducibility. As an example, repeat enzyme-linked immunosorbent assays (ELISA) for antibodies to Borrelia burgdorferi, the etiologic agent of Lyme disease, are used. These repeat tests were part of the 1991 Quality Control Assessment of provincial laboratories that was carried out by the Laboratory Centre for Disease Control (Ottawa). Twenty-seven sera from cases and non-cases were tested by three laboratories, and two laboratories repeated the tests once. Methodological issues discussed include: different methods of assessing reproducibility in the continuous scale; whether reproducibility should be assessed with data in continuous or categorical form; problems assessing the reproducibility of data that has been standardized using a calibration-regression line; and problems with external generalizability of reproducibility studies of rare diseases. The authors conclude that the statistical method used to assess the reproducibility of a test must be adjusted to suit individual study designs and data, and the usage of the test.

Intra- and interlaboratory reproducibility of an ELISA serological test for Lyme disease.

OBJECTIVES: Lyme disease has been increasingly diagnosed throughout North America since the late 1970s. The clinical diagnosis and epidemiological monitoring of Lyme disease are aided by serological testing for the etiological agent, Borrelia burgdorferi. Numerous authorities have questioned the reproducibility of these serological tests. This study assessed the intra- and interlaboratory reproducibility of an elisa used to aid in the diagnosis of Lyme disease. METHODS: Twenty-seven sera from cases and noncases were tested by three laboratories. Two of the laboratories repeated the tests once. These testings were part of the 1991 quality control assessment of provincial laboratories carried out by the Laboratory Centre for Disease Control (lcdc), Ottawa. RESULTS: The mean weighted kappa statistics were 0.87 for interlaboratory comparisons and 0.89 for intralaboratory comparisons. CONCLUSIONS: Overall, the elisa assessed in this study demonstrated good to excellent intra- and interlaboratory reproducibility in the lcdc 1991 quality control assessment when the data were assessed in the categorical scale using the weighted kappa statistic. Generalization of these findings to clinical laboratory settings must be done with caution.