Maria F. Lorenzi

Cancer risk in aluminum reduction plant workers (Canada)

A 14-year update to a previously published historical cohort study of aluminum reduction plant workers was conducted [1]. All men with three or more years at an aluminum reduction plant in British Columbia (BC), Canada between the years 1954 and 1997 were included; a total of 6,423 workers. A total of 662 men were diagnosed with cancer, representing a 400% increase from the original study. Standardized mortality and incidence ratios were used to compare the cancer mortality and incidence of the cohort to that of the BC population. Poisson regression was used to examine risk by cumulative exposure to coal tar pitch volatiles (CTPV) measured as benzene soluble materials (BSM) and benzo(a)pyrene (BaP). The risk for bladder cancer was related to cumulative exposure to CTPV measured as BSM and BaP (p trends <0.001), and the risk for stomach cancer was related to exposure measured by BaP (p trend BaP <0.05). The risks for lung cancer (p trend <0.001), non-Hodgkin lymphoma (p trend <0.001), and kidney cancer (p trend <0.01) also increased with increasing exposure, although the overall rates were similar to that of the general population. Analysis of the joint effect of smoking and CTPV exposure on cancer showed the observed dose–response relationships to be independent of smoking.

Hospital-related morbidity among childhood cancer survivors in British Columbia, Canada: Report of the childhood, adolescent, young adult cancer survivors (CAYACS) program

Our study examines inpatient, hospital‐related morbidity in a geographically‐defined cohort of long‐term cancer survivors diagnosed before age 20 years in the province of British Columbia (BC), Canada. A total of 1374 survivors diagnosed from 1981 to 1995 surviving at least 5‐years postdiagnosis, and a matched sample of 13,740 BC residents, were identified from population registers, and linked to provincial hospitalization records from 1986 to 2000. Logistic regression was used to assess relative risk and effect of sociodemographic, clinical, and temporal factors on risk. Approximately 41% of survivors vs. 17% of the population sample had at least one type of hospitalization‐related late morbidity in the observation period (adjusted RR 4.1, 95% CI 3.7–4.5). Those at highest risk were survivors of leukemia (RR 4.8, 95% CI 4.0–5.8), central nervous system tumors (RR 4.8, 95% CI 4.0–5.8), bone and soft tissue sarcomas (RR 4.9, 95% CI 3.8–6.2), and kidney cancer (RR 4.9, 95% CI 3.4–7.0). Adjusted relative risk was elevated for all types of morbidity except pregnancy and birth complications, and highest for neoplasms (including second primary cancers) (RR 21.7, 95% CI 16.3–28.7). Morbidity was elevated for all combinations of primary treatment and highest for those with previous radiation, chemotherapy, and surgery (RR 7.1, 95% CI 5.5–9.0). Over time, morbidity for late effects other than neoplasms became more prevalent. These results suggest that survivors are at increased ongoing risk of many types of hospital‐related late morbidity, implying that long‐term monitoring for multiple health problems is warranted.

Childhood, adolescent, and young adult cancer survivors research program of British Columbia: Objectives, study design, and cohort characteristics†

The Childhood, Adolescent, and Young Adult Cancer Survivors Research Program (CAYACS) has been established in the province of British Columbia (BC), Canada, to carry out research into late effects and survivor care in multiple domains, and to inform policy and practice.

Antidepressant use among survivors of childhood, adolescent and young adult cancer: A report of the childhood, adolescent and young adult cancer survivor (CAYACS) research program†

Although survivors of childhood, adolescent, and young adult (AYA) cancer are at risk for late psychological sequelae, it is unclear if they are more likely to be prescription antidepressant users than their peers.

Comparison of two indices of exposure to polycyclic aromatic hydrocarbons in a retrospective aluminium smelter cohort

Background: The association between coal tar-derived substances, a complex mixture of polycyclic aromatic hydrocarbons, and cancer is well established. However, the specific aetiological agents are unknown. Objective: To compare the dose–response relationships for two common measures of coal tar-derived substances, benzene-soluble material (BSM) and benzo(a)pyrene (BaP), and to evaluate which among these is more strongly related to the health outcomes. Methods: The study population consisted of 6423 men with ⩾3 years of work experience at an aluminium smelter (1954–97). Three health outcomes identified from national mortality and cancer databases were evaluated: incidence of bladder cancer (n = 90), incidence of lung cancer (n = 147) and mortality due to acute myocardial infarction (AMI, n = 184). The shape, magnitude and precision of the dose–response relationships and cumulative exposure levels for BSM and BaP were evaluated. Two model structures were assessed, where 1n(relative risk) increased with cumulative exposure (log-linear model) or with log-transformed cumulative exposure (log–log model). Results: The BaP and BSM cumulative exposure metrics were highly correlated (r = 0.94). The increase in model precision using BaP over BSM was 14% for bladder cancer and 5% for lung cancer; no difference was observed for AMI. The log-linear BaP model provided the best fit for bladder cancer. The log–log dose–response models, where risk of disease plateaus at high exposure levels, were the best-fitting models for lung cancer and AMI. Conclusion: BaP and BSM were both strongly associated with bladder and lung cancer and modestly associated with AMI. Similar conclusions regarding the associations could be made regardless of the exposure metric.

Chronic and Acute Effects of Coal Tar Pitch Exposure and Cardiopulmonary Mortality Among Aluminum Smelter Workers

Air pollution causes several adverse cardiovascular and respiratory effects. In occupational studies, where levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) are higher, the evidence is inconsistent. The effects of acute and chronic PAH exposure on cardiopulmonary mortality were examined within a Kitimat, Canada, aluminum smelter cohort (n = 7,026) linked to a national mortality database (1957-1999). No standardized mortality ratio was significantly elevated compared with the provinces population. Smoking-adjusted internal comparisons were conducted using Cox regression for male subjects (n = 6,423). Ischemic heart disease (IHD) mortality (n = 281) was associated with cumulative benzo[a]pyrene (B(a)P) exposure (hazard ratio = 1.62, 95% confidence interval: 1.06, 2.46) in the highest category. A monotonic but nonsignificant trend was observed with chronic B(a)P exposure and acute myocardial infarction (n = 184). When follow-up was restricted to active employment, the hazard ratio for IHD was 2.39 (95% confidence interval: 0.95, 6.05) in the highest cumulative B(a)P category. The stronger associations observed during employment suggest that risk may not persist after exposure cessation. No associations with recent or current exposure were observed. IHD was associated with chronic (but not current) PAH exposure in a high-exposure occupational setting. Given the widespread workplace exposure to PAHs and heart diseases high prevalence, even modest associations produce a high burden.

Late morbidity leading to hospitalization among 5-year survivors of young adult cancer: a report of the childhood, adolescent and young adult cancer survivors research program.

To estimate the risk of late morbidity leading to hospitalization among young adult cancer 5‐year survivors compared to the general population and to examine the long‐term effects of demographic and disease‐related factors on late morbidity, a retrospective cohort of 902 five‐year survivors of young adult cancer diagnosed between 1981 and 1999 was identified from British Columbia (BC) Cancer Registry. A matched comparison group (N = 9020) was randomly selected from the provincial health insurance plan. All hospitalizations until the end of 2006 were determined from the BC health insurance plan hospitalization records. The Poisson regression model was used to estimate the rate ratios for late morbidity leading to hospitalization except pregnancy after adjusting for sociodemographic and clinical risk factors. Overall, 455 (50.4%) survivors and 3,419 (37.9%) individuals in the comparison group had at least one type of late morbidity leading to hospitalization. The adjusted risk of this morbidity for survivors was 1.4 times higher than for the comparison group (95% CI = 1.22–1.54). The highest risks were found for hospitalization due to blood disease (RR = 4.2; 95% CI = 1.98–8.78) and neoplasm (RR = 4.3; 95% CI = 3.41–5.33). Survivors with three treatment modalities had three‐fold higher risk of having any type of late morbidity (RR = 3.22; 95% CI = 2.09–4.94) than the comparators. These findings emphasize that young adult cancer survivors still have high risks of a wide range of late morbidities.

Hospitalisations 1998-2000 in a British Columbia population-based cohort of young cancer survivors: report of the Childhood/Adolescent/Young Adult Cancer Survivors (CAYACS) Research Program.

BACKGROUND AND OBJECTIVES Because of late effects among survivors of cancer in young people, increased hospitalisations would be expected. This study determined the occurrence, frequency and days in hospital (DIH) of hospital admissions among 5-year survivors of childhood and adolescent cancer diagnosed in British Columbia (BC), compared hospitalisation risk with the general population and examined the impact of sociodemographic, health care system and clinical factors. DESIGN This population-based study frequency matched 1157 survivors of cancer diagnosed before 20 years of age from 1970 to 1992 from the BC Cancer Registry with 11,570 randomly selected individuals from BCs health insurance plan Client Registry. Administrative hospitalisation records from 1998 to 2000 were linked to study cohorts, and regression and trend analyses were carried out. RESULTS From 1998 to 2000, 240 (21%) of survivors and 614 (5.3%) of the population sample were admitted to hospital at least once [adjusted OR=4.36 (95% CI 3.68-5.16)]. Hospitalised survivors had a higher average number of admissions (2.0 versus 1.5 admissions, respectively) and longer mean DIH (10.9 versus 7.8d, respectively) than hospitalised population controls. Female gender and older age increased the risk of hospitalisation, as did the presence of a relapse or second cancer by 5 years post-diagnosis. CONCLUSION Our cohort of child and adolescent cancer survivors had higher odds of hospitalisation, more admissions among those hospitalised and longer stay in hospital compared to the population sample. This has implications for health care system resources and appropriate management of late effects of survivors.

Reclassification of ICD-9 Codes into Meaningful Categories for Oncology Survivorship Research

Background. The International Classification of Disease, ninth revision (ICD-9) is designed to code disease into categories which are placed into administrative databases. These databases have been used for epidemiological studies. However, the categories used in the ICD9-codes are not always the most effective for evaluating specific diseases or their outcomes, such as the outcomes of cancer treatment. Therefore a re-classification of the ICD-9 codes into new categories specific to cancer outcomes is needed. Methods. An expert panel comprised of two physicians created broad categories that would be most useful to researchers investigating outcomes and morbidities associated with the treatment of cancer. A Senior Data Coordinator with expertise in ICD-9 coding, then joined this panel and each code was re-classified into the new categories. Results. Consensus was achieved for the categories to go from the 17 categories in ICD-9 to 39 categories. The ICD-9 Codes were placed into new categories, and subcategories were also created for more specific outcomes. The results of this re-classification is available in tabular form. Conclusions. ICD-9 codes were re-classified by group consensus into categories that are designed for oncology survivorship research. The novel re-classification system can be used by those involved in cancer survivorship research.

Antidepressant use among survivors of childhood, adolescent, and young adult cancer: Letter to the editor response

To the Editor: Although Kawada’s letter raised interesting points, we feel his concerns are unjustified and his choice of a comparable study inappropriate. His first concern is that he feels we have insufficient events per variable in our regression models for stratified analyses.We did not actually conduct stratified analyses in our study of antidepressant use among childhood cancer survivors [1]. We report 4,951 antidepressant prescriptions (events) with a total of four independent variable categories (cancer survivorship, urban/rural status, socioeconomic status, and attained age), composed of a total of 11 parameters in our primary multivariable regression model. For descriptive purposes, we divided antidepressants into categories and repeated the analysis with the same independent variables. Among six drug categories, five had a minimum of 692 events (prescriptions filled), which clearly meets the suggested 10–20 events per variable. We agree that there were a small number of events in the final category (monoamine oxidase inhibitors), and that this odds ratio, with its associated wide confidence interval, must be interpreted with caution. Similarly, Kawada was concerned that our number of events (n1⁄4 515) in the survivor-only analysis is insufficient. In this analysis we had seven independent variable categories, composed of a total of 27 variables in the regressionmodel. Again, this satisfies the minimum guideline of 10 events per variable. Kawada suggested that gender should be included in the logistic regression model for anti-depressant use among survivors and general population comparators. Since survivors and comparators were matched by gender, the addition of gender does not affect the estimate of risk of antidepressant use for survivors compared to the general population. In our survivor-only analysis we reported an increased likelihood of antidepressant use in female survivors (OR 2.02; 95% CI 1.63, 2.50). There was a similar increased risk for females in the general population (OR 1.88; 95% CI 1.76, 2.01). Both female and male survivors were more likely than comparators of the same sex to fill antidepressant prescriptions (ORfemale 1.23; 95% CI 1.07, 1.41; ORmale 1.19; 95% CI 1.01, 1.40). Kawada then compared our results to a study with a very different outcome; the risk of hospital contact for mental disorders among survivors [2]. Kawada focused on unipolar depression, however, antidepressants are prescribed for a much broader range of clinical indications. Finally, Kawada took issue with our lack of a clear relationship between age at childhood cancer diagnosis and risk of antidepressant use years later. Again, comparison is made with a study evaluating a different outcome [2]. Lund et al. found that survivors diagnosed at younger ages had a higher risk of hospital contact for mental disorders than those diagnosed at older ages. Using hospital contact as an outcome will not capture survivors who are filling antidepressant prescriptions as outpatients, making comparisons difficult. We found that the likelihood of antidepressant drug use, adjusted for attained age, increased with increasing time from diagnosis (P-trend1⁄4 0.026) in our universal health care systemwith stable access to care [3]. This novel finding highlights the ongoing needs of cancer survivors years after treatment and warrants further investigation.