Cohort cancer incidence among pulp and paper mill workers in British Columbia.

OBJECTIVES: A study was conducted to investigate cancer risks in a cohort of pulp and paper workers. METHODS: All male workers with > or =1 years of employment in 14 pulp and paper mills in 1950-1992 were studied. Standardized incidence ratios (SIR) were used to compare the cancer incidence of the cohort with that of the Canadian male population. Record linkage with the National Cancer Registry was performed using the generalized iterative record linkage method. RESULTS: Altogether 1756 cancer cases were observed in the entire cohort. For > or =15 years of work, the entire cohort had significantly increased SIR values for pleural and prostate cancer and skin melanoma; there was also a significantly increased risk for skin melanoma among workers in the kraft process only, rectal cancer among workers in the sulfite process only, and stomach and prostate cancer and all leukemias combined among workers in both the kraft and sulfite processes. A separate analysis comparing workers in pulping and papermaking with those in the pulping process only did not reveal any difference in cancer risk and hence did not modify the results. The SIR values for skin melanoma were not significantly increased in a comparison using the British Columbia male population. Nine of 10 pleural cancers were mesotheliomas, which likely reflect past asbestos exposure. CONCLUSIONS: The results suggest that long-term work in the pulp and paper industry is associated with excess risks of prostate and stomach cancers and all leukemias for work in both kraft and sulfite processes and of rectal cancer for work in the sulfite process only.

First analysis of cancer incidence and occupational radiation exposure based on the National Dose Registry of Canada.

A cohort study was conducted to investigate the relation between cancer incidence and occupational exposure to ionizing radiation. Records containing dose information from 1951 to 1988 for 191,333 persons were extracted from the National Dose Registry of Canada. The records were linked to the Canadian Cancer Data Base, with incidence data from 1969 to 1988. Standardized incidence ratios were calculated using Canadian cancer incidence rates stratified by age, sex, and calendar year. Excess relative risks were obtained from internally based dose-response analyses. The following significant results were found for males and females combined: a deficit in the standardized incidence ratio for all cancers combined; elevated standardized incidence ratios for thyroid cancer and melanoma; and elevated excess relative risks for rectum, leukemia, lung, all cancers combined, all except lung, and all except leukemia. For males, cancers of the colon, pancreas, and testis also showed significantly elevated excess relative risks. The specific cancer types listed above have been implicated in previous studies on occupational exposure to ionizing radiation, except for testis, colon, and melanoma, while the findings on thyroid cancer from previous studies are inconclusive. The thyroid standardized incidence ratios in this study are highly significant, but further investigation is needed to assess the possibility of association with occupational radiation exposure.

Identification of occupational cancer risks in British Columbia. A population-based case-control study of 995 incident breast cancer cases by menopausal status, controlling for confounding factors.

Lifetime occupational histories as well as information on known and suspected breast cancer risk factors were collected by means of a self-administered questionnaire from 1018 women with incident breast cancer ascertained from the British Columbia Cancer Registry, and from 1020 population controls. A matched case-control study design was used. Conditional logistic regression for matched sets data and the likelihood ratio were used in a two-step procedure and were performed separately for pre-menopausal women, post-menopausal women, and for all cases combined. Excess risk was noted for several white-collar occupations. Significantly increased risk was observed: (1) among pre-menopausal women: in electronic data-processing operators; barbers and hairdressers; in sales and material processing occupations; and in the food, clothing, chemical and transportation industries; (2) among post-menopausal women: in schoolteaching; in medicine, health, and nursing occupations; in laundry and dry-cleaning occupations; and in the aircraft and automotive, including gasoline service station, industries. Several significant associations were also seen in the combined group of pre- and post-menopausal women, particularly in crop farmers and in the fruit and vegetable, publishing and printing, and motor vehicle repair industries. The results of this study suggest excess breast cancer risk in a number of occupations and industries, notably those that entail exposure to solvents and pesticides.

Identification of occupational cancer risks in British Columbia. Part I: Methodology, descriptive results, and analysis of cancer risks, by cigarette smoking categories of 15,463 incident cancer cases.

To identify occupational cancer risk factors, lifetime occupational, smoking, and alcohol-consumption histories were collected by means of a self-administered questionnaire from 15,463 male cancer patients aged 20 years and over as ascertained from the British Columbia population-based cancer registry; all cases were histologically confirmed. The study methodology, descriptive results, and cancer risks from cigarette smoking are reported. Assessment of questionnaire validation and reliability showed very high correlations between all variables analysed. Non-response bias, assessed among 221 non-responders and 432 matched controls, revealed no statistically significant differences for smoking status, education, or for 11 usual (longest-held job) occupational groups, except for managerial occupations and for four pooled groups that represented 6.7% of all occupations. Except for pancreatic cancer, a significant relationship was found for all cancer sites known to be strongly associated with cigarette smoking.

Identification of occupational cancer risks in British Columbia. Part II: A population-based case-control study of 1516 Prostatic cancer cases.

We have, as part of a program aimed at detecting occupational risk factors in British Columbia, collected lifetime occupational histories from 15,643 incident cancer cases, of whom 1519 had a diagnosis of prostate cancer. Occupational risks for this cancer site are examined using this large data set, and the results are presented in this report.

Occupational risk factors for prostate cancer mortality in British Columbia, Canada.

BACKGROUND: Although prostate cancer is the most common life-threatening cancer among males in North America, relatively little is known about its etiology. We have conducted a proportional mortality study to generate hypotheses concerning occupational risk factors for the disease. METHODS: Age standardized proportional mortality ratios (PMR) for prostate cancer were calculated for a total of 216 occupations and 88 industries. Separate calculations were done for all male deaths age 20 and up and for deaths that occurred during men's working lifetime (age 20-65). RESULTS: Elevated mortality from prostate cancer was seen among business owners and managers (PMR = 110; 95% CI = 101-118), brokers (PMR = 184; 95% CI = 122-266), farmers and farm managers (PMR = 112; 95% CI = 105-120), and school teachers (PMR = 133; 95% CI = 101-174). Evaluation by industry shows elevated prostate cancer mortality in agriculture (PMR = 110; 95% CI = 103-118), financial institutions (PMR = 138, 95% CI = 112-170), and transportation equipment manufacture (PMR = 136; 95% CI = 109-168). CONCLUSIONS: The findings suggest that workers in a number of occupations have elevated risks of prostate cancer including farmers and teachers. More detailed cohort and case-control studies, evaluating specific exposures are required before primary prevention programs in the workplace are feasible.

First analysis of mortality and occupational radiation exposure based on the National Dose Registry of Canada.

A cohort mortality study of occupational radiation exposure was conducted using the records of the National Dose Registry of Canada. The cohort consisted of 206,620 individuals monitored for radiation exposure between 1951 and 1983 with mortality follow-up through December 31, 1987. A total of 5,426 deaths were identified by computerized record linkage with the Canadian Mortality Data Base. The standardized mortality ratio for all causes of death was 0.61 for both sexes combined. However, trends of increasing mortality with cumulative exposure to whole body radiation were noted for all causes of death in both males and females. In males, cancer mortality appeared to increase with cumulative exposure to radiation, without any clear relation to specific cancers. Unexplained trends of increasing mortality due to cardiovascular diseases (males and females) and accidents (males only) were also noted. The excess relative risk for both sexes, estimated to be 3.0% per 10 mSv (90% confidence interval 1.1-4.8) for all cancers combined, is within the range of risk estimates previously reported in the literature.

Reducing cervical cancer among First Nations women.

First Nations women in British Columbia have a four to six times higher mortality rate from cancer of the cervix than do women in the general population. Their participation in the provincial Cervical Cytology Screening Program (CCSP) is less regular and less frequent than other women in B.C. Likewise, they have more difficulty in obtaining culturally suitable health care services from respectful and consistent professionals. These issues should be of critical concern to nurses, as nurses provide the majority of health services to First Nations people.

Cohort mortality study of pulp and paper mill workers in British Columbia, Canada.

The authors studied a cohort of 30,157 male pulp and paper workers in British Columbia, Canada. Of these, 20,373 worked in kraft mills only, 5,249 in sulfite mills only, and 4,535 in both kraft and sulfite mills. All workers with at least 1 year of employment on January 1, 1950, or thereafter until December 31, 1992, were studied. Standardized mortality ratios (SMRs) were used to compare the mortality rates of the cohort with those of the Canadian male population. Ninety percent confidence intervals (CIs) for the SMRs were obtained. Cancer risks significantly associated with work duration and time from first employment of 15 years or more were observed: 1) total cohort: pleura (SMR = 3.61, 90% CI 1.42-7.58); kidney (SMR = 1.69, 90% CI 1.13-2.43); brain (SMR = 1.51, 90% CI 1.03-2.16); 2) workers in kraft mills only: kidney (SMR = 1.92, 90% CI 1.04-3.26); 3) workers in sulfite mills only: Hodgkin's disease (SMR = 4.79, 90% CI 1.29-12.37); 4) workers ever employed in both kraft and sulfite mills: esophagus (SMR = 1.91, 90% CI 1.00-3.33). These malignancies have been associated with the following known or suspected carcinogens to which pulp and paper workers may have been exposed: asbestos (pleura), biocides (kidney), formaldehyde (kidney, brain, Hodgkin's disease), hypochlorite (esophagus). A nested case-control study with detailed exposure assessment is under way to help determine whether excess risks for specific cancers reflect exposure among subsets of workers.

Cervical cytology screening. How can we improve rates among First Nations women in urban British Columbia?

OBJECTIVE: To determine Pap smear screening rates among urban First Nations women in British Columbia; to identify facilitators and barriers; and to develop, implement, and evaluate specific interventions to improve Pap smear screening in Vancouver. DESIGN: Computer records of band membership lists and the Cervical Cytology Screening Program registry were compared to determine screening rates; personal interviews and community meetings identified facilitators and barriers to urban screening programs. A community advisory committee and the project team collaborated on developing specific interventions. SETTING AND PARTICIPANTS: Purposive sample of British Columbia First Nations women, focusing on women living in Vancouver. INTERVENTIONS: Poster, art card, and follow-up pamphlet campaign; articles in First Nations community papers; community meetings; and Pap smear screening clinics for First Nations women. MAIN OUTCOME MEASURES: Pap smear screening rates among BC First Nations women according to residence and reasons for not receiving Pap smears. RESULTS: Pap smear screening rates were substantially lower among First Nations women than among other British Columbia women; older women had even lower rates. No clear differences were found among First Nations women residing on reserves, residing in Vancouver, or residing off reserves elsewhere in British Columbia. Facilitators and barriers to screening were similar among women residing on reserves and in Vancouver. Many First Nations women are greatly affected by health care providers' attitudes, abilities to provide clear information, and abilities to establish trusting relationships. CONCLUSIONS: Family physicians are an important source of information and motivation for Pap smear screening among First Nations women.

Cohort study of Air Canada pilots: mortality, cancer incidence, and leukemia risk.

Despite the special working environment and exposures of airline pilots, data on risk of death and cancer incidence in this occupational group are limited. The authors investigated a cohort of 2,740 Air Canada pilots who contributed 62,449 person-years of observation. All male pilots employed for at least 1 year on and since January 1, 1950, were studied. The cutoff date for outcome information was December 31, 1992. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare mortality rates and cancer incidence rates of the cohort with the respective Canadian population rates. Ninety percent confidence intervals of the SMR and SIR were calculated. Statistically significant decreased mortality was observed for all causes (SMR = 0.63, 90% confidence interval (CI) 0.56-0.70), for all cancers (SMR = 0.61, 90% CI 0.48-0.76), and for all noncancer diseases (SMR = 0.53, 90% CI 0.45-0.62). Mortality from aircraft accidents was significantly raised (SMR = 26.57, 90% CI 19.3-35.9). Significantly decreased cancer incidence was observed for all cancers (SIR = 0.71, 90% CI 0.61-0.82), rectal cancer (SIR = 0.42, 90% CI 0.14-0.96), lung cancer (SIR = 0.28, 90% CI 0.16-0.46), and bladder cancer (SIR = 0.36, 90% CI 0.12-0.82). Prostate cancer (SIR = 1.87, 90% CI 1.38-2.49) and acute myeloid leukemia (SIR = 4.72, 90% CI 2.05-9.31) were significantly increased. The preferred relative risk model for radiation-induced nonchronic lymphoid leukemia (Beir V report) was applied to the cohort by using published estimates of in-flight radiation exposures. The estimated relative risk ranged from 1.001 to 1.06 and did not differ significantly from the observed SIR (SIR = 1.88, 90% CI 0.80-3.53). However, the incidence rate of acute myeloid leukemia was significantly increased. Monitoring of in-flight radiation exposure and long-term follow-up of civil aviation crew members is needed to further assess cancer incidence and leukemia risk in this special occupational group.

Clinical determinants of mammographic dysplasia patterns.

The association between the clinical manifestations of benign breast disease (BBD) and mammographic patterns was investigated among 1394 women (923 pre-menopausal and 471 post-menopausal) participating to the Canadian National Breast Screening Study in Vancouver, who completed a questionnaire designed to collect detailed information on the symptoms and signs of BBD, hormonal, reproductive and dietary factors. Mastalgia was present in 637 (46%) women and was cyclical in 505 (79%). Breast swelling was noted in 331 women (23%) and mammary dysplasia involving 50% or more of the breast parenchyma in 733 (43%). Mastalgia was highly associated with breast swelling (odds ratios [OR] = 29.9, 95% confidence interval [CI] = 21.3-41.8), particularly when cyclical and characterized by tenderness with pain (OR = 58.4, 95% CI = 39.1-87.0). The relative risk for mammary dysplasia involving 50% or over of the breast parenchyma was significant in pre-menopausal women having breast swelling (OR = 2.96, 95% CI = 1.81-4.83), being highest in women with cyclical mastalgia associated with tenderness and pain (OR = 3.43, 95% CI = 1.49-7.92); similar associations were noted in post-menopausal women. This study indicates that mastalgia is strongly related to breast swelling, especially when tenderness is associated with pain. Furthermore, mastalgia associated with breast swelling is highly related to the presence of mammary dysplasia involving 50% or more of the breast parenchyma in both pre- and post-menopausal women, suggesting that cyclical tenderness and breast swelling may carry an increased breast cancer risk.

Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine.

The authors compared, in a double-blind, randomized, crossover study in 13 healthy adult volunteers, the single- and multiple-dose pharmacokinetics, relative bioavailability, and side effects of a new oral sustained-release formulation of codeine (SRC) containing 150 mg codeine base, with oral immediate-release codeine phosphate (IRC). Sustained-release codeine was given at a dose of 150 mg every 12 hours for 5 doses; IRC was given at a dose of 60 mg (2 x 30 mg) every 4 hours for the first 3 doses, and 30 mg every 4 hours thereafter for 12 doses. Plasma codeine levels were determined using a sensitive and specific high-performance liquid chromatography method and corrected for dose administered and codeine base equivalent. Mean values for single-dose pharmacokinetic parameters for SRC and IRC, respectively, were: Cmax of 217.8 and 138.8 ng/mL; Tmax of 2.3 and 1.1 hours; AUC0-inf of 1202.3 and 1262.4 ng.mL-1.hour-1; and t1/2el of 2.6 hours for both formulations. Their respective mean steady-state pharmacokinetic parameters were: Cmax of 263.8 and 222.9 ng/mL; Tmax of 3.2 and 1.1 hours; AUC0-12h of 1576.4 and 1379.1 ng.mL-1.hour-1; and t1/2el of 2.8 and 2.3 hours. These results indicate comparable bioavailability between both formulations with SRC providing delayed peak plasma levels. The sustained-release character of SRC can be explained by a delayed absorption, which is not limiting to drug elimination. Sustained-release codeine provides higher plasma codeine levels over a broader time interval and is expected to improve pain management.

Mortality among female registered nurses and school teachers in British Columbia.

The mortality profile of female nurses and teachers in British Columbia (BC) was examined using age-standardized proportional mortality ratios (PMRs) calculated for the period 1950-1984. Lowered overall mortality among nurses was seen for degenerative heart disease and for cerebrovascular accidents. Significantly elevated PMR values were observed for cancer of the breast and ovary in nurses of age 20-65 years. PMRs were significantly elevated for cancer of the pancreas and leukemia among those age 20 years and older. Elevated values were also observed for motor vehicle accidents and suicide among nurses in both age groups. Lower than expected mortality from degenerative heart disease and cerebrovascular accidents was seen in working age teachers (age 20-65 years). However, elevated PMRs were detected for carcinoma of the colon, breast, endometrium, brain, and melanoma. Among those 20 years and over, significantly elevated PMRs were also observed for cancers of the ovary and other digestive organs. Elevated PMRs were found for motor vehicle and aircraft accidents. Mortality from cirrhosis of the liver was lower than anticipated in both teachers and nurses. A number of significant PMRs declined when deaths of "homemakers" were withdrawn from the comparison group used to generate PMR values, suggesting that risk of death from various causes among women working outside the home differ from those seen in women who are predominantly in the home.

Cervical cancer screening in Canadian Native women. Adequacy of the Papanicolaou smear.

Cervical cancer mortality remains high in Canadian Native women in British Columbia. Underutilization of the Provincial Cytology Screening Program by Canadian Native women has been documented. Another potential factor is the quality of specimens obtained. Proportions of unsatisfactory smears and smears lacking endocervical cells, which reflect the sampling technique, were compared between Canadian Native and other British Columbian women. The findings suggest that differences in the quality of cytologic smears do not explain the observed discrepancy in cervical cancer mortality between Canadian Native and non-Native populations.

History of lactation and breast cancer risk.

A self-administered questionnaire was completed by 1,018 women diagnosed with breast cancer during 1988-1989 identified through the British Columbia Cancer Registry and by 1,025 controls selected at random from the Provincial Voters List. Parous premenopausal women who had never nursed (odds ratio (OR) = 1.3, 95% confidence interval (CI) 0.9-2.0) or who had lactated for 1 month or less (OR = 1.8, 95% CI 1.3-2.5) had an increased risk of breast cancer adjusted for age and parity, compared with women who had breast-fed 2 months or longer. The risk was particularly elevated (OR = 3.0, 95% CI 1.6-5.4) among women who reported having tried to nurse, but who were unsuccessful. Among women who nursed for at least 2 months, there was an indication of decreasing risk with increasing duration of nursing. Among postmenopausal parous women, no relation between lactation history and breast cancer risk was evident.

Rate of death from cervical cancer among native Indian women in British Columbia.

OBJECTIVE: To compare the rates of death from cervical cancer among native Indian women and non-native women in British Columbia from 1953 to 1984. DESIGN: Retrospective analysis of data retrieved from the British Columbia Division of Vital Statistics. MAIN OUTCOME MEASURES: Age-standardized death rate and relative rate. RESULTS: The rate of death from cervical cancer was significantly higher among the native women than among the non-native women throughout the study period. No deaths from cervical cancer were recorded in women under 20 years of age. Among those 20 to 64 the relative rate increased from 3.83 in 1953-62 to 6.53 in 1973-84; among those 65 or more it decreased slightly. For the entire study period the relative rate for women 20 to 64 years old was 5.95 and for those 65 or older 2.98. CONCLUSION: The rate of death from cervical cancer among native women in British Columbia is unacceptably high, probably because the provincial screening program does not reach as many native women as it does non-native women.

The evaluation of analgesic effects in cancer patients as exemplified by a double-blind, crossover study of immediate-release versus controlled-release morphine.

We compared the effects of controlled-release and immediate-release morphine preparations in adult patients with moderate-to-severe cancer pain and report methodologic approaches to pain evaluation. The study consisted of a two-phase randomized crossover trial preceded by a titration phase; all phases were conducted under double-blind conditions. To evaluate pain intensity, a visual analogue scale (VAS) and the Present Pain Intensity scale of the McGill Pain Questionnaire were used. Additional morphine solution for breakthrough pain was used as an outcome measure. Pain was evaluated nine times daily, which permitted correlation of pain scores with the pharmacokinetic patterns of the test drugs. Side effects were rated once daily, using a scale from 0 to 3. To assess the relative importance of side effects, a toxicity index was designed based on both the intensity and duration of each side effect. The overall VAS pain scores during treatment with controlled-release and immediate-release morphine were 1.3 (SD = 0.1) and 1.4 (SD = 0.2), respectively. Use of supplemental morphine solution for breakthrough pain expressed as the percentage of the daily dose of the test drug was 5.5% for the controlled-release drug and 10.9% for the immediate-release drug. Differences in pain scores, side effects, and supplemental morphine requirement between the two groups were not significant. We discuss methodologic issues in double-blind clinical trials of analgesics, in particular the validity of "Patient Preference" as an outcome measure and problems related to the titration phase.