Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology.

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case-control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.

Mesothelioma, asbestos, and reported history of cancer in first-degree relatives.

BACKGROUND: Although malignant mesothelioma is known to be strongly related to asbestos exposure, its relationship to familial factors is unclear. METHODS: We compared reported histories of cancer in first-degree relatives, obtained from telephone interviews with the next-of-kin of 196 patients who had a pathologic diagnosis of mesothelioma, and with those from 511 decreased controls. RESULTS: Among men exposed to asbestos, we found a statistically significant twofold elevation in the risk of mesothelioma for patients reporting cancer in two or more first-degree relatives. We found no significant elevation in women or among the small number of men without asbestos exposure. The next-of-kin of three patients (but no controls) reported a possible mesothelioma in a first-degree relative; asbestos exposure could not be ruled out in those relatives. Associations of asbestos with pleural mesothelioma were stronger among men with a reported family history of cancer than men without, although no statistical evidence of an interaction was detected. CONCLUSIONS: These results provide suggestive, but limited, evidence that a family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma given asbestos exposure.

Malignant mesothelioma: attributable risk of asbestos exposure.

OBJECTIVES: To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS: Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. RESULTS: Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. CONCLUSIONS: Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive.

Vasectomy and prostate cancer risk: methodological review of the evidence.

Two recent studies have reported a significantly elevated risk of prostate cancer among vasectomized men. To assess whether the new results conflict with earlier studies that found no significant overall association, and, if so, whether such a conflict could have a methodological basis, we reviewed the six major epidemiological studies of this topic. Statistical analysis revealed significant (p < 0.01) heterogeneity among the associations in the six studies, attributable to one of the recent studies. Scrutiny of the studies for fulfillment of eight methodological standards for scientific validity revealed that no study completely fulfilled more than four standards, and that all studies were deficient in avoiding detection bias and obtaining accurate vasectomy histories. Our review indicates that the evidence on this topic is indeed conflicting, that the quality of the evidence does not resolve the conflict, and that future studies of this topic, designed to ensure scientific credibility of results, are needed.

PIP: 2 recent studies have reported a significantly elevated risk of prostate cancer among vasectomized men. 6 major relevant epidemiological studies were reviewed to determine the new results conflicted with earlier studies finding no significant association and whether such conflict was attributable to methodological deficiencies. Statistical analysis indicated significant heterogeneity among the associations in the 6 studies (p 0.01) imputed to one of the studies. Examination of 8 methodological standards for scientific validity showed that none of the studies fulfilled more than 4 standards, and all were deficient in avoiding detection bias and obtaining accurate vasectomy histories. The evidence is conflicting concerning prostate cancer, and future studies are needed to ensure scientific credibility of results. The literature search included the MEDLINE bibliographic database from January 1970 to December 1991, which yield 6 studies on the link of vasectomy and risk of prostate cancer. The 8 criteria were prior hypothesis, single underlying suitable validated histories of vasectomy, protection against detection bias, valid diagnoses of prostate cancer, and incident prostate cancer outcomes. 1 was a cohort and 5 were case-control investigations during 1982-88. The follow-up after vasectomy varied: 15+, 20+, 30+, and 44 years with 40-86 years of documented ages. Analysis of homogeneity indicated similarity for 5 studies. Estimation of overall effect by odds ration estimates and confidence intervals suggested a slight risk of prostate cancer associated with vasectomy. Control for confounding by age was done in 5 studies, and no study was given credit for adequate protection against detection bias. 3 studies reported histological confirmation of prostate cancer, but none reported a review of diagnostic evidence validated with vasectomy histories.

Retrospective cohort mortality study of workers at an aircraft maintenance facility. I. Epidemiological results.

A retrospective cohort study of 14,457 workers at an aircraft maintenance facility was undertaken to evaluate mortality associated with exposures in their workplace. The purpose was to determine whether working with solvents, particularly trichloroethylene, posed any excess risk of mortality. The study group consisted of all civilian employees who worked for at least one year at Hill Air Force Base, Utah, between 1 January 1952 and 31 December 1956. Work histories were obtained from records at the National Personnel Records Centre, St. Louis, Missouri, and the cohort was followed up for ascertainment of vital state until 31 December 1982. Observed deaths among white people were compared with the expected number of deaths, based on the Utah white population, and adjusted for age, sex, and calendar period. Significant deficits occurred for mortality from all causes (SMR 92, 95% confidence interval (95% CI) 90-95), all malignant neoplasms (SMR 90, 95% CI 83-97), ischaemic heart disease (SMR 93, 95% CI 88-98), non-malignant respiratory disease (SMR 87, 95% CI 76-98), and accidents (SMR 61, 95% CI 52-70). Mortality was raised for multiple myeloma (MM) in white women (SMR 236, 95% CI 87-514), non-Hodgkin's lymphoma (NHL) in white women (SMR 212, 95% CI 102-390), and cancer of the biliary passages and liver in white men dying after 1980 (SMR 358, 95% CI 116-836). Detailed analysis of the 6929 employees occupationally exposed to trichloroethylene, the most widely used solvent at the base during the 1950s and 1960s, did not show any significant or persuasive association between several measures of exposure to trichloroethylene and any excess of cancer. Women employed in departments in which fabric cleaning and parachute repair operations were performed had more deaths than expected from MM and NHL. The inconsistent mortality patterns by sex, multiple and overlapping exposures, and small numbers made it difficult to ascribe these excesses to any particular substance. Hypothesis generating results are presented by a variety of exposures for causes of death not showing excesses in the overall cohort.

Retrospective cohort mortality study of workers at an aircraft maintenance facility. II. Exposures and their assessment.

Methods are presented that were used for assessing exposures in a cohort mortality study of 15,000 employees who held 150,000 jobs at an Air Force base from 1939 to 1982. Standardisation of the word order and spelling of the job titles identified 43,000 unique job title organisation combinations. Walkthrough surveys were conducted, long term employees were interviewed, and available industrial hygiene data were collected to evaluate historic exposures. Because of difficulties linking air monitoring data and use of specific chemicals to the departments identified in the work histories, position descriptions were used to identify the tasks in each job. From knowledge of the tasks and the chemicals used in those tasks the presence or absence of 23 chemicals or groups of chemicals were designated for each job organisation combination. Also, estimates of levels of exposure were made for trichloroethylene and for mixed solvents, a category comprising several solvents including trichloroethylene, Stoddard solvent, carbon tetrachloride, JP4 gasoline, freon, alcohols, 1,1,1-trichloroethane, acetone, toluene, methyl ethyl ketone, methylene chloride, o-dichlorobenzene, perchloroethylene, chloroform, styrene, and xylene.

Atypical squamous cells. A case-series study of the association between papanicolaou smear results and human papillomavirus DNA genotype.

Thirty women with "atypical" squamous cells but not cervical intraepithelial neoplasia (CIN) on their Papanicolaou smears were tested for the presence of human papillomavirus (HPV) with the Southern blot hybridization technique. The Papanicolaou smears were reviewed for the presence of atypical squamous cells according to Patten's criteria. Comparison groups consisted of 30 patients with normal, 29 patients with CIN I and 24 patients with CIN II Papanicolaou smears. Ten of the 30 women (33%) with atypical cells on Papanicolaou smears were positive for HPV DNA as compared to 17% with normal and 59% with CIN I or II Papanicolaou smears. HPV 16 was present in 70-80% of the HPV DNA-positive patients in each Papanicolaou smear group. Concurrent CIN was also identified on colposcopically directed biopsies in 27% of the patients with squamous atypia. Patients with atypical squamous cells on Papanicolaou smears had coexisting HPV infection and CIN in about one-third of the cases. Colposcopy and further follow-up are recommended for such patients.

Cancer mortality among a cohort of chromium pigment workers.

A study of mortality among 1,879 male workers employed in a New Jersey chromium pigment factory was carried out, with follow-up from 1940 to 1982. Vital status of 1,737 (92%) of the eligible cohort members was determined. For all malignant neoplasms, 101 deaths were observed while 108.8 were expected, SMR = 93 (standardized mortality ratio; n.s.). For the entire study group, no significant excess was observed for respiratory cancer or cancer at other sites. However, the total number of years of employment in the factory and the total number of years of exposure to chromate dusts were both statistically significantly (p less than .05, for trend) associated with an increased risk for lung cancer. The excess risk for lung cancer associated with duration of exposure to chromate dusts was, however, only clearly apparent for subjects followed for 30 years or more after initial employment. For this group, the SMRs were 81, 139, 201, and 321 for the subjects with 0 years, less than 1 year, 1-9 years, and 10+ years of exposure to chromate dusts (p less than .01, for trend), respectively. The risk for digestive cancer was only weakly associated with exposure to chromate dusts.

Survival patterns for malignant mesothelioma: the SEER experience.

Statistical analyses of 1,475 histologically confirmed cases of malignant mesothelioma ascertained through the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute for the years 1973-1984 showed age at diagnosis, sex, stage of disease, type of treatment, and geographic area of residence to be important predictors of patient survival, although type of treatment may be confounded with prognostic factors (patients selected for surgical treatment tended to have better performance status than other patients). Women below the age of 50 had an unusually long survival, even after adjustment for the effects of other variables in the model. A relatively large proportion of female cases had site of disease designated as peritoneum, but site was not a significant prognostic factor. These results suggest that age, gender and stage of disease should be carefully considered in designing and analyzing clinical trials for persons with mesothelioma. Survival was shorter in the 4 SEER registries which had shipbuilding as a major industry than in the others with less potential asbestos exposure, offering weak support for the hypothesis that asbestos-exposed cases of mesothelioma have worse survival experience than other cases.

Demographic patterns for mesothelioma in the United States.

Incidence rates for pleural and peritoneal mesotheliomas in about 10% of the U.S. population were examined by various demographic characteristics based on 1973-84 data from the Surveillance, Epidemiology, and End Results Program. Although pleural mesothelioma was more common than peritoneal mesothelioma, both are rare diseases in this country. Pleural mesothelioma incidence rates among white males increased over time and were highest in seaboard areas where shipyards have been located (Seattle, San Francisco-Oakland, Hawaii). The significant secular change was attributed to both period (date of diagnosis) and cohort (date of birth) effects. Pleural mesothelioma incidence rates among white males were nearly 50% higher in the 1980-84 period compared to those in 1975-79; the cohort effect rose to a peak for the 1905-9 birth cohort and then declined. These effects probably reflect changes in asbestos exposure patterns in the past and more recent changes in clinical awareness and coding rules for mesothelioma. Geographic analysis of U.S. death certificates for pleural cancer among white males and females dying during 1968-78 indicated that mortality rates were significantly elevated in several areas that have had asbestos-manufacturing plants or shipyards. Analyses of mortality rates must be viewed with caution, since mesothelioma is considerably underreported on death certificates.

Identification and classification of carcinogens: procedures of the Chemical Substances Threshold Limit Value Committee, ACGIH. American Conference of Governmental Industrial Hygienists.

The Chemical Substances Threshold Limit Value Committee of the American Conference of Governmental Industrial Hygienists has refined its procedures for evaluating carcinogens. Types of epidemiologic and toxicologic evidence used are reviewed and a discussion is presented on how the Committee evaluates data on carcinogenicity. Although it has not been conclusively determined whether biological thresholds exist for all types of carcinogens, the Committee will continue to develop guidelines for permissible exposures to carcinogens. The Committee will continue to use the safety factor approach to setting Threshold Limit Values for carcinogens, despite its shortcomings. A compilation has been developed for lists of substances considered to be carcinogenic by several scientific groups. The Committee will use this information to help to identify and classify carcinogens for its evaluation.

Recent trends in mesothelioma incidence in the United States.

Mesothelioma incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City), Los Angeles County, California, and the SEER Program of the National Cancer Institute were analyzed for trends, using original cancer registry diagnoses. Results indicate a significant increase in incidence during 1973-80 for pleural mesothelioma among white males older than 55 at time of diagnosis but not for other age-race-sex-site subgroups. A histopathologic review of New York State and Los Angeles County cases by two independent pathologists, expert in the diagnosis of mesothelioma, lowered the overall estimates but a significant upward trend remained. The observed trend does not appear to be related to changes in diagnostic practice. The results of a five-member panel of expert pathologists will be published in a separate methodology paper.

Brain and central nervous system cancer mortality in U. S. rubber workers.

Since 1963 the observed mortality experience of BCNS cancers among rubber workers appears to be very comparable to that expected. A possible exception to this statement is the experience of one plant in Akron, Ohio, reported by Monson and Nakano. Excesses in earlier years may also be localized to one or two companies. The results of a case-control study did not support a hypothesized association of elevated BCNS cancer risk with exposures in the tire building/tire assembly segments of the rubber tire manufacturing process. The direction of future epidemiologic studies would benefit by the assembly of as large a number of cases as possible and should focus on calendar periods of exposure, make allowance for a latent period, and include retrospective industrial hygiene assessments of the specific exposures.

Applications of a job classification system in occupational epidemiology.

An occupational preventive medicine program attempts to control exposure so workers experience no detrimental effect on health. In a chemically complex industry, the definition of exposure is difficult because of the many different chemicals used and produced, the many different jobs and processes with qualitatively different exposures, and the movement of workers from job to job. Jobs have therefore been grouped on the basis of process or product into functionally homogeneous categories called occupational titles (OT's). Work experience can now be quantified independent of exposure (or by the dominant toxicants in each OT) and compared to health outcomes. Examples are discussed of the application of OT's to studies of the mortality and morbidity experience in the rubber industry, and the development of dose-response relations.

Mortality among rubber workers: Relationship to specific jobs.

This study has examined the ten-year mortality in a single-plant population of 6678 male rubber workers, in terms of the association of specific causes of death with a history of having worked in certain categories of jobs within the rubber industry. The work-histories of individual study subjects were analyzed, in detail, for all workers dying of selected causes of death. Comparison was made with the work-histories of a 22% age-stratified random sample of the total population. Age-adjusted exposure ratios (Tables 3 and 4) were calculated for all nine case groups in all 16 work areas, using differing exposure criteria (i.e. duration and calendar period). These ratios provide an approximation of the increased mortality risk associated with particular work areas. The risk ratios (with their associated confidence intervals), in Table 5, provide more rigorous estimates of these instances of increased mortality risk. For each cause of death studied, there were statistically significant associations with several work areas. For the cancers, the strongest associations tended to be with work areas at the front end of the production line (especially compounding and mixing), where the likelihood of contact with dusts, chemical ingredients, and vapors containing the early reaction byproducts, is high. The reclaim operation and the synthetic plant were each associated with several cancers (respiratory and bladder, and stomach and lymphato-hematopoietic cancers, respectively). The lymphatic leukemias were associated with solvent-exposure areas, especially inspection, finishing, and repair. Ischemic heart disease deaths, at ages 40-54, were strongly associated with having worked in extrusion and tread cementing, and in the synthetic plant. Deaths from diabetes mellitus were strongly associated with the janitoring-trucking category, and with jobs in the inspection, finishing and repair area. These observed associations, calculated after controlling for the variables sex and age, were apparently not due to confounding by smoking and race differences between work areas. The role of selective transfer of sick individuals (into, say janitoring or trucking) warrants further investigation. However, this mechanism is unlikely to be involved in the great majority of the observed associations. Another possible source of spurious inferences of increased risk would be correlation, within work-histories, between two job categories, one of which actually involved increased risk, while the other did not. Such associations could occur if certain job sequency trends existed within this working population. (Preliminary analyses indicate that this likelihood is not great; however, further analysis is planned.) Detailed study of specific environmental agents, historically and cross-sectionally, is currently underway, in an attempt to identify the work-environment agents responsible for the associations reported here.

The association of vinyl chloride exposures with morbidity symptoms.

A mail-out questionnaire examined symptoms previously associated with vinyl chloride exposure. Assessment of exposure levels was made by analytical measurement and observation. The resulting statistical analysis revealed a dose-response type of relationship between exposure and certain morbidity symptoms.