Prostate cancer risk and exposure to pesticides in British Columbia farmers.

BACKGROUND: Several epidemiologic studies have reported an increased risk of prostate cancer among farmers. Our aim was to assess the risk of developing prostate cancer in relation to exposure to specific active compounds in pesticides. METHOD: A case-control approach was used with 1,516 prostate cancer patients and 4,994 age-matched internal controls consisting of all other cancer sites excluding lung cancer and cancers of unknown primary site. Lifetime occupational history was obtained through a self-administered questionnaire and used in conjunction with a job exposure matrix to estimate the participants' lifetime cumulative exposure to approximately 180 active compounds in pesticides. Conditional logistic regression was used to assess prostate cancer risk, adjusting for potential confounding variables and effect modifiers. These include age, ethnicity, alcohol consumption, smoking, education, and proxy respondent. RESULTS AND CONCLUSIONS: The significant association between prostate cancer risk and exposure to DDT (OR = 1.68; 95% CI: 1.04-2.70 for high exposure), simazine (OR = 1.89; 95% CI: 1.08-3.33 for high exposure), and lindane (OR = 2.02; 95% CI: 1.15-3.55 for high exposure) is in keeping with those previously reported in the literature. We also observed a significant excess risk for several active ingredients that have not been previously reported in the literature such as dichlone, dinoseb amine, malathion, endosulfan, 2,4-D, 2,4-DB, and carbaryl. Some findings in our study were not consistent with those reported in the literature, including captan, dicamba, and diazinon. It is possible that these findings showed a real association and the inconsistencies reflected differences of characteristics between study populations.

The birth of the subspecialty of medical oncology and examples of its early scientific foundations.

"Passion is not accepting defeat."--Emil Frei III. In the early 1950s, an experimental and clinical program characterized by unique cross-fertilization was developed. The clinical importance of experimental animal models in drug screening and in establishing key chemotherapy concepts and the role of the pioneers of medical oncology in the design of the various phases of drug trials, using childhood acute leukemia and breast cancer as models, are discussed. Over a short time and with only a few drugs, principles of chemotherapy were laid out, which led to cures in such diseases as childhood acute leukemia and Hodgkin's disease and to improved disease-free survival in breast cancer. It is these and other achievements that paved the way to medical oncology. At the instigation of the American Society of Clinical Oncology (ASCO), the American Board of Internal Medicine made inquiries about a subspecialty in oncology. ASCO and B. J. Kennedy, MD, played key roles in the events leading to the official recognition of medical oncology as a new subspecialty of internal medicine in 1972.

Health outcomes of low-dose ionizing radiation exposure among medical workers: a cohort study of the Canadian national dose registry of radiation workers.

BACKGROUND: Medical workers can be exposed to low-dose ionizing radiation from various sources. The potential cancer risks associated with ionizing radiation exposure have been derived from cohort studies of Japanese atomic bomb survivors who had experienced acute, high-level exposure. Since such extrapolations are subject to uncertainty, direct information is needed on the risk associated with chronic low-dose occupational exposure to ionizing radiation. OBJECTIVES: To determine the occupational doses of ionizing radiation and examine possible associations with mortality rates and cancer incidence in a cohort of medical workers deriving from the National Dose Registry of Canada (NDR) over the period of 1951-1987. METHODS: Standardized mortality and incidence ratios (SMR and SIR, respectively) were ascertained by linking NDR data for a cohort of 67 562 medical workers (23 580 males and 43 982 females) with the data maintained by the Canadian Mortality, and Cancer Incidence databases. Dosimetry information was obtained from the National Dosimetry Services. RESULTS: During the follow-up period, 1309 incident cases of cancer (509 in males, 800 in females) and 1325 deaths (823 in males, 502 in females) were observed. Mortality from cancer and non-cancer causes was generally below expected as compared to the general Canadian population. Thyroid cancer incidence was significantly elevated both among males and females, with a combined SIR of 1.74 and 90% CI: 1.40-2.10. CONCLUSIONS: The findings confirm previous reports on an increased risk of the thyroid cancer among medical workers occupationally exposed to ionizing radiation. Over the last 50 years, radiation protection measures have been effective in reducing radiation exposures of medical workers to the current very low levels.

Low dose ionizing radiation exposure and cardiovascular disease mortality: cohort study based on Canadian national dose registry of radiation workers.

OBJECTIVES: The purpose of our study was to assess the risk of cardiovascular disease (CVD) mortality in a Canadian cohort of 337 397 individuals (169 256 men and 168 141 women) occupationally exposed to ionizing radiation and included in the National Dose Registry (NDR) of Canada. MATERIAL AND METHODS: Exposure to high doses of ionizing radiation, such as those received during radiotherapy, leads to increased risk of cardiovascular diseases. The emerging evidence of excess risk of CVDs after exposure to doses well below those previously considered as safe warrants epidemiological studies of populations exposed to low levels of ionizing radiation. In the present study, the cohort consisted of employees at nuclear power stations (nuclear workers) as well as medical, dental and industrial workers. The mean whole body radiation dose was 8.6 mSv for men and 1.2 mSv for women. RESULTS: During the study period (1951-1995), as many as 3 533 deaths from cardiovascular diseases have been identified (3 018 among men and 515 among women). In the cohort, CVD mortality was significantly lower than in the general population of Canada. The cohort showed a significant dose response both among men and women. Risk estimates of CVD mortality in the NDR cohort, when expressed as excess relative risk per unit dose, were higher than those in most other occupational cohorts and higher than in the studies of Japanese atomic bomb survivors. CONCLUSIONS: The study has demonstrated a strong positive association between radiation dose and the risk of CVD mortality. Caution needs to be exercised when interpreting these results, due to the potential bias introduced by dosimetry uncertainties, the possible record linkage errors, and especially by the lack of adjustment for non-radiation risk factors.

Identification of occupational cancer risk in British Columbia: a population-based case-control study of 2,998 lung cancers by histopathological subtype.

BACKGROUND: Few studies have investigated occupational lung cancer risk in relation to specific histopathological subtypes. METHODS: A case-control study was conducted to evaluate the relationship between lung cancer and occupation/industry of employment by histopathological subtype. A total of 2,998 male cases and 10,223 cancer controls, diagnosed between 1983 and 1990, were identified through the British Columbia Cancer Registry. Matched on age and year of diagnosis, conditional logistic regression analyses were performed for two different estimates of exposure with adjustment for potentially important confounding variables, including tobacco smoking, alcohol consumption, marital status, educational attainment, and questionnaire respondent. RESULTS: For all lung cancers, an excess risk was observed for workers in the primary metal (OR = 1.31, 95% CI, 1.01-1.71), mining (OR = 1.53, 95% CI, 1.20-1.96), machining (OR = 1.33, 95% CI, 1.09-1.63), transport (OR = 1.50, 95% CI, 1.08-2.07), utility (OR = 1.60, 95% CI, 1.22-2.09), and protective services (OR = 1.27, 95% CI, 1.05-1.55) industries. Associations with histopathological subtypes included an increased risk of squamous cell carcinoma in construction trades (OR = 1.25, 95% CI, 1.06-1.48), adenocarcinoma for professional workers in medicine and health (OR = 1.73, 95% CI, 1.18-2.53), small cell carcinoma in railway (OR = 1.62, 95% CI, 1.06-2.49), and truck transport industries (OR = 1.51, 95% CI, 1.00-2.28), and large cell carcinoma for employment in the primary metal industry (OR = 2.35, 95% CI, 1.11-4.96). CONCLUSIONS: Our results point to excess lung cancer risk for occupations involving exposure to metals, polyaromatic hydrocarbons and asbestos, as well as several new histopathologic-specific associations that merit further investigation.

Male bladder cancer risk and occupational exposure according to a job-exposure matrix-a case-control study in British Columbia, Canada.

OBJECTIVES: The authors investigated the risk of bladder cancer in association with exposure to over 12 000 occupational chemical agents, complex mixtures, and other substances (hereafter referred to as chemical agents). METHODS: Adult males diagnosed with cancer between 1983 and 1990 in British Columbia, Canada, were surveyed. Detailed occupational histories and confounding information was provided by a self-administered questionnaire. Cancer controls were matched to bladder cancer cases, resulting in 1062 cases and 8057 controls for the analysis. An extensive United-States-based job-exposure matrix was applied to estimate cumulative exposure to occupational chemical agents. Odds ratios for bladder cancer due to exposure to chemical agents were estimated via conditional logistic regression analyses, adjusted for important confounders. RESULTS: A significantly (P<0.05) increased risk was detected for ever exposure to 635 chemical agents, and 341 chemical agents exhibited a significantly increasing dose-response relationship. Adjustment for multiple comparisons resulted in a subset of 29 chemical agents that continued to show significant results. A principal components analysis classified these 29 chemical agents into five independent groups, distinguished mainly by job. Exposures to these chemical agents were largely due to employment in the logging and construction industries and occupations involving motor vehicles. Consistent results were observed for bladder carcinogens reported in the literature. CONCLUSIONS: This study suggests that several specific chemical agents were significantly associated with the risk of bladder cancer. The chemical agents were mainly derivatives or combustion products of fossil fuels. The results corroborate important findings from the literature and document a risk for specific chemical agents not previously reported.

Identification of occupational cancer risks in British Columbia: a population-based case-control study of 1129 cases of bladder cancer.

OBJECTIVE: We collected information on lifetime occupational histories, smoking, and alcohol consumption from 15,463 incident cancer cases. Occupational risk factors for bladder cancer are presented in this report. METHOD: A matched case-control design was used. All cases were diagnosed with bladder cancers, with controls being internal controls consisting of all other cancer sites, excluding lung and unknown primary. Data were analyzed using conditional logistic regression for matched sets data and the likelihood ratio test. RESULTS: Excess bladder cancer risks was observed in a number of occupation and industries, particularly those involving exposure to metals, including aluminum, paint and solvents, polycyclic aromatic hydrocarbons, diesel engine emissions, and textiles. CONCLUSIONS: The results of our study are in line with those from the literature and further suggest that exposure to silica and to electromagnetic fields may carry an increased risk of bladder cancer.

A hierarchical approach to coding chemical, biological and pharmaceutical substances.

This hierarchical coding system is designed to classify substances into successively subordinate categories on the basis of chemical, physical and biological properties. Although initially developed for occupational cancer epidemiological studies, it is general in nature and can be used for other purposes where a systematic approach is needed to catalogue or analyze large numbers of substances and/or physical properties. The coding system incorporates a multi level approach, where substances can be coded both on the basis of function and composition. On the first level, a three digit code is assigned to each substance to indicate its primary use in the occupational environment (e.g. pesticide, catalyst, adhesive). Substances can then be coded using a ten digit code to indicate structure and composition (e.g. organic molecule, biomolecule, pharmaceutical). Depending on the complexity required, analysis can incorporate the three digit code, ten digit code, or a combination of both. The approach to coding both chemical and biological agents is modeled in part after conventional approaches used by the International Union of Pure and Applied Chemists (IUPAC) and the International Union of Biochemists (IUB). Development of the coding system was initiated in the 1980's in response to a need for a system allowing analysis of individual agents as well classes or groups of substances. The project was undertaken as a collaborative venture between the BC Cancer Agency, Cancer Control Research program (then Division of Epidemiology) and the Department of Chemical and Biological Engineering at the University of British Columbia.

Decreases in occupational exposure to ionizing radiation among Canadian dental workers.

OBJECTIVE: To describe doses of ionizing radiation and their possible associations with mortality rates and cancer incidence among Canadian dental workers. METHODS: The National Dose Registry (NDR) of Canada was used to assess occupational dose of ionizing radiation received by dental workers. The NDR cohort includes 42,175 people classified as dental workers. Subjects in the NDR were linked to both the Canadian Mortality Database and the Canadian Cancer Database to ascertain cause of death and cancer incidence, respectively. RESULTS: The cohort consisted of 9,051 male and 33,124 female dental workers. A total of 656 incident cases of cancer and 558 deaths were observed. The standardized mortality ratio associated with all-cause mortality was 0.53 (90% confidence interval [CI] 0.49-0.57). The incidence of cancer among dental workers was lower than that for the Canadian population for all cancers except melanoma of the skin (for melanoma, the standardized incidence ratio was 1.46 [90% CI 1.14-1.85]). Occupational doses of ionizing radiation among dentists and dental workers have decreased markedly since the 1950s. CONCLUSIONS: Dental workers receive very low doses of ionizing radiation, and these doses do not appear to be associated with any increase in cancer incidence; the increased incidence of melanoma is more likely related to other risk factors such as exposure to ultraviolet radiation from sunlight.

Identification of occupational cancer risks in British Columbia: a population-based case-control study of 769 cases of non-Hodgkin's lymphoma analyzed by histopathology subtypes.

We have, as part of a program aimed at detecting occupational risk factors in British Columbia, collected lifetime occupational histories as well as information on lifetime cigarette smoking and alcohol consumption from 15,643 incident cancer cases, of whom 782 had a diagnosis of non-Hodgkin's lymphoma (NHL). Occupational risks for this cancer site are examined using a matched case-control study design, and the results are presented in this report for all cases and for histopathology subtypes. The results of our study indicate excess NHL risk, particularly for a number of occupations that involve exposures to electromagnetic fields, treated and fresh wood, metals, and solvents.

Do work-related breast cancer risks in pre-menopausal women depend on family history?

Our objective was to determine work-related pre-menopausal breast cancer risks that depend on a woman's family history of the disease. In a large case-control study, 318 women with breast cancer and 340 healthy women completed a mailed questionnaire. All of the women were pre-menopausal and controls were matched to cases by age. All risk estimates were adjusted for women's smoking history and whether they reported a prior breast biopsy. There was an odds ratio (OR) of 6.9 (95% confidence interval: 1.5-31.9) for breast cancer among pre-menopausal women with no family history if they ever worked in material processing occupations. Among women with a family history of breast cancer, there was an OR of 6.4 (0.7-55.9) if they ever worked as miscellaneous salesclerks and salespersons of commodities, and an OR of 5.7 (0.6-50.9) if they ever worked in department stores. Despite changes in the OR, none of the estimates were significantly different in women with and without a family history.

Carcinogenic and endocrine disrupting effects of cigarette smoke and risk of breast cancer.

BACKGROUND: Results of epidemiological studies, assessing the relation between smoking and breast cancer, have been inconclusive. Our aim was to assess the carcinogenic and possibly antioestrogenic effects of cigarette smoke on risk of breast cancer. METHODS: We sent a questionnaire to 1431 women younger than age 75 years who had breast cancer and were listed on the population-based British Columbia cancer registry between June 1, 1988, and June 30, 1989. We also sent questionnaires to 1502 age-matched controls, randomly selected from the 1989 provincial voters list. We obtained information on all known and suspected risk factors for breast cancer, and on lifetime smoking, alcohol consumption, and occupational history. We assessed the effect of smoking separately for premenopausal and postmenopausal women, adjusting for confounding variables. FINDINGS: 318 premenopausal women and 340 controls replied. Risk of breast cancer was significantly increased (adjusted odds ratio 1.69, 95% CI 1.13-2.51) in women who had been pregnant and who started to smoke within 5 years of menarche, and in nulliparous women who smoked 20 cigarettes daily or more (7.08, 1.63-30.8) and had smoked for 20 cumulative pack-years or more (7.48, 1.59-35.2). Postmenopausal women (700 breast cancer and 685 controls) whose body-mass index increased from age 18 to current and who started to smoke after a first fullterm pregnancy had a significantly reduced risk of breast cancer (0.49, 0.27-0.89). INTERPRETATION: Our results suggest that cigarette smoke exerts a dual action on the breast, with different effects in premenopausal and postmenopausal women. Our observations reinforce the importance of smoking prevention, especially in early adolescence, and draw attention to the timing of exposure in relation to susceptibility and refractory windows in the design of studies to investigate associations between environmental carcinogens or putative endocrine disruptors and risk of breast cancer.

Assessment of adult cancer pain: shortcomings of current methods.

The evaluation of cancer pain remains a problematic clinical problem, not only due to the subjective and multidimensional nature of pain per se, but also because of its specific characteristics. Cancer pain has an insidious onset, often involves many sites, and is frequently multicausal. Tools have been developed to quantify pain, the most commonly used being the verbal rating scale (VRS), the visual analogue scale (VAS), and the McGill Pain Questionnaire (MPO). The first 2 scales are short, easy to administer and to score, but only measure pain intensity. The VRS is assumed to be an ordinal scale although unequal differences between pain descriptors have been demonstrated; it offers a restrictive choice of words that may not represent pain experience with sufficient precision, and is not sensitive to change especially for mild pain. The VAS on the other hand, represents pain as a continuum and is sensitive to change. The MPQ has the advantage of evaluating the sensory, affective and evaluative dimensions of pain. However, it is lengthy to administer and some words are not readily understandable. In addition, the words within a given category are considered to be equidistant, the number of words in each category are unequal, and the number of categories evaluating a given dimension are not taken into account when calculating the total pain rating index. A further issue in assessing pain, other than the choice of a valid and reliable tool, is the frequency with which pain evaluations should be repeated. To date no studies have addressed this problem.(ABSTRACT TRUNCATED AT 250 WORDS)