Serum concentrations of DDE, PCBs, and other persistent organic pollutants and mammographic breast density in Triana, Alabama, a highly exposed population.

INTRODUCTION: Although some persistent organic pollutants (POPs) are considered human carcinogens, results from studies evaluating exposures and breast cancer risk have been inconsistent, potentially related to varying ages at exposure. Additionally, few studies evaluated the association between POPs exposure and mammographic breast density (MBD), an intermediate biomarker of breast cancer risk. We carried out a cross-sectional study to investigate associations between serum POPs concentrations and MBD measured in 1998 in female residents of Triana, Alabama, in a predominately African American population with high POPs exposures, particularly to p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane). METHODS: We measured lipid-adjusted serum concentrations (ng/g lipid) of p,p'-DDT and its main metabolite p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), polychlorinated biphenyls (PCBs), ß-hexachlorocyclohexane (ß-HCCH), heptachlor epoxide, oxychlordane, trans-nonachlor, mirex, and aldrin for each woman in our study (n = 210). We also measured two MBD metrics, percent MBD (%MBD) and area of MBD (aMBD). Using adjusted Spearman correlation coefficients (rs) we evaluated correlations between %MBD and aMBD with individual POPs in the overall population and by age group (19-40, 41-54, and 55-91 years) and also estimated adjusted mean measures of MBD with 95% confidence intervals across tertiles of analytes using generalized linear models (GLM). We calculated p-values for multiplicative interaction by age group using GLM. Additional analyses excluded women with current hormone replacement therapy (HRT) use and evaluated early-life exposure (prior to age 18) during the heaviest contamination period in Triana (1947-90). RESULTS: Among all women, we found no correlation between p,p'-DDE and %MBD, but after age stratification and exclusion of HRT users, there was a suggestion of a difference by age group, with younger women having a weak positive correlation (rs = 0.12, p = 0.37) and older women having a weak negative correlation (rs = -0.12, p = 0.43); pinteraction = 0.06. In contrast, PCBs were weakly positively correlated with %MBD among all women, with the correlation magnitudes increasing after excluding current HRT users (rs-total PCBs = 0.17, p = 0.03). After age stratification and exclusion of HRT users, correlations for PCBs were higher among younger and middle-age women, with only a handful of these correlations being statistically significant. For ß-HCCH, the strongest finding was a negative correlation among older women (rs = -0.26, p = 0.07). Correlations were positive predominantly in the younger age group for heptachlor epoxide (rs = 0.27, p = 0.04), oxychlordane (rs = 0.35, p = 0.006), and trans-nonachlor (rs = 0.37, p = 0.003), and largely null for the middle and older age groups; pinteraction range: 0.03-0.05. Similar patterns were found in GLM analyses using tertiles of exposure and aMBD as the metric for MBD. Women exposed during the heaviest chemical contamination period in Triana prior to age 18 had positive correlations between %MBD and PCBs, heptachlor epoxide, mirex, oxychlordane, and trans-nonachlor. CONCLUSIONS: In this population, despite high exposures to p,p'-DDT and thus high serum concentrations of its main metabolite, p,p'-DDE, we did not find strong evidence of a positive association with MBD. In fact, there was some evidence of a negative association among older women for p,p'-DDE; a similar pattern was found for ß-HCCH. However, younger women with higher serum levels of PCBs, heptachlor epoxide, oxychlordane, and trans-nonachlor, who were likely exposed in early life, had higher MBD. These findings should be replicated in larger studies.

Investing in prospective cohorts for etiologic study of occupational exposures.

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures.

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph).

BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

The National Bladder Cancer Study: employment in the chemical industry.

The relationship between bladder cancer employment in the chemical industry was assessed in a study of 2,982 incident cases and 5,782 population controls. There were 190 cases and 369 controls who had ever been employed in the chemical industry [odds ratio (OR) = 1.0; 95% confidence interval (CI) = 0.8, 1.2]. Employment in the production of organic chemicals was associated with a 1.3-fold increased risk among men (95% CI = 0.8, 2.1). Risk increased with duration of employment, reaching an OR of 2.4 for 20 or more years (chi for trend = 1.57; P = .06). Women who had worked in the plastics industry had a 3.3-fold increased bladder cancer risk. Within the plastics and rubber industry, increased risks for bladder cancer were found for men in mixing, filtering, grinding, and other dusty operations (OR = 4.6; 95% CI = 1.0, 20.4) and men in heat-associated operations (OR = 2.8; 95% CI = 0.5, 15.3). A 1.4-fold risk among men in agricultural chemicals was attributable to risks in the pesticides subdivision (OR = 2.3; 95% CI = 0.6, 8.2). Men performing dusty operations (i.e., mixing, filtering, sifting, grinding, and crushing) in any industry had an OR of 1.4 (95% CI = 0.8, 2.7). Despite the large number of study subjects, few statistically significant findings were observed and should be evaluated with consideration of the large number of comparisons made in the analysis. The statistical power of case-control studies to detect risks associated with particular occupational exposures is limited by the small proportion of the population employed in any specific occupation or industry.

Pesticides and non-Hodgkin's lymphoma.

The incidence of non-Hodgkin's lymphoma (NHL) has increased over 50% in the last 15 years. This paper reviews the possible role of pesticides in this increase. While small increases in risk of NHL among farmers have been observed in general occupational surveys, recent studies focusing on specific pesticides have observed much larger risks. Frequent use of phenoxyacetic acid herbicides, in particular, 2,4-dichlorophenoxyacetic acid, has been associated with 2- to 8-fold increases of NHL in studies conducted in Sweden, Kansas, Nebraska, Canada, and elsewhere. Canine malignant lymphoma has also been associated with dog owner use of 2,4-dichlorophenoxyacetic acid and commercial lawn pesticide treatments. There are much fewer data linking NHL to other types of pesticides, but triazine herbicides, organophosphate insecticides, fungicides, and fumigants have also been associated with increased risk of NHL. Pesticide exposures are not limited to agricultural populations but are widespread in the general population through use on lawns, golf courses, rights-of-way, and elsewhere. Since the use of pesticides, particularly phenoxy herbicides, has increased dramatically preceding and during the time period in which the incidence of NHL has increased, they could have contributed to the rising incidence of NHL.

Case-control study of diet and mesothelioma in Louisiana.

Data were analyzed from a case-control interview study of malignant mesothelioma in Louisiana, which gathered information on usual diet and on lifetime occupational exposure to asbestos. Thirty-seven patients with malignant mesothelioma of the pleura (n = 32) or peritoneum (n = 5) were matched to controls according to age, sex, race, and factors related to case ascertainment (hospital and date of diagnosis, or parish and date of death). Twenty-one of the 37 cases were judged by masked occupational review to have been exposed to asbestos (57%), compared to seven of 37 controls (19%). Seven additional cases and 10 additional controls had occupational histories suggestive of asbestos exposure. With regard to usual diet before illness, cases reported less frequent consumption of homegrown produce (p = 0.005), cruciferous vegetables (p = 0.005), and all vegetables combined (p = 0.09) than did the controls. An estimate of usual carotene intake was also significantly lower in cases (p = 0.03). Dose-dependent reductions in risk were seen with increasing consumption of vegetables, especially cruciferous vegetables (p for trend = 0.013). These associations were not explained by differences in asbestos exposure as measured by the occupational review. The results indicate that consumption of vegetables or some vegetable-related constituent may have a protective effect on developing mesothelioma.

Risk of female breast cancer associated with serum polychlorinated biphenyls and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene.

This case-control study was designed to investigate the relationship between polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2'-bis(p-chlorophenyl)ethylene (DDE) and breast cancer risk in Connecticut. Cases were incident breast cancer patients who were either residents of Tolland County or who had a breast-related surgery at the Yale-New Haven Hospital in New Haven County. Controls were randomly selected from Tolland County residents or from patients who had newly diagnosed benign breast diseases or normal tissue at Yale-New Haven Hospital. A total of 475 cases and 502 controls had their serum samples analyzed for PCBs and DDE in 1995-1997. The age- and lipid-adjusted geometric mean serum level of DDE was comparable between the cases (460.1 ppb) and controls (456.2 ppb). The geometric mean serum level of PCBs was also comparable between cases (733.1 ppb) and controls (747.6 ppb). After adjustment for confounding factors, odds ratios of 0.96 (95% confidence interval, 0.67-1.36) for DDE and 0.95 (95% confidence interval, 0.68-1.32) for PCBs were observed when the third tertile was compared with the lowest. Further stratification by parity, lactation, and menopausal and estrogen receptor status also showed no significant association with serum levels of DDE or PCBs. The results by PCB congener groups also showed no major increased risk associated with any of the congener groups. Our study does not support the hypothesis that DDE and PCBs, as encountered through environmental exposure, increase the risk of female breast cancer.

Environmental exposure to hexachlorobenzene (HCB) and risk of female breast cancer in Connecticut.

Earlier studies have provided inconclusive results relating hexachlorobenzene (HCB), an organochlorine fungicide, to female breast cancer risk. The current study, with a total of 304 breast cancer cases and 186 controls recruited in Connecticut between 1994 and 1997, examined the association by directly comparing breast adipose tissue levels of HCB between incident breast cancer cases and noncancer controls. The cases and controls were patients who had breast biopsies or surgery at the Yale-New Haven Hospital (New Haven, CT) and histologically diagnosed either as breast cancer or benign breast disease. Information on major known or suspected risk factors for breast cancer was obtained through in-person interview by trained interviewers. No significant difference in mean breast adipose tissue levels of HCB was observed between breast cancer patients (21.0 ppb) and controls (19.1 ppb) in this large case-control study. The risk also did not vary significantly by menopausal status, estrogen or progesterone receptor status of the breast cancer cases, breast cancer histology, stage of diagnosis, or type of benign breast disease. Among parous women who reported ever breast feeding, an odds ratio (OR) of 0.5 [95% confidence interval (CI), 0.2-1.4] was observed when the highest quartile was compared with the lowest quartile. However, no association was observed among parous women who reported never breast feeding (OR = 0.7; 95% CI, 0.3-1.7 for the fourth quartile). For nulliparous women, the adjusted OR was 2.1 (95% CI, 0.5-8.8) for the third tertile when compared with the lowest based on few subjects. Therefore, our study does not support a positive association between environmental exposure to HCB and risk of breast cancer.

Use of hair colouring products and breast cancer risk: a case-control study in Connecticut.

This case-control study was designed to test the hypothesis that the risk of breast cancer varies by type and colour of the hair colouring products used. A total of 608 cases and 609 controls were included in the study. We found no increased risk associated with the overall use of hair dye products or exclusive use of permanent or temporary types of hair dye products. Among those who reported to have exclusively used semi-permanent types of hair colouring products, some of the ORs were elevated. However, none of the ORs related to age at first use, duration of use, total number of applications, and years since first use, was statistically significant. There was also no increased risk of breast cancer associated with exclusive use of dark or light hair colouring products, or use of mixed types or colours of hair dye products. We also found no increased risk of breast cancer associated with hair dye use based on an individual's reason for using a hair colouring product, such as to cover grey or to change natural hair colour. These data suggest that the use of hair colouring products does not have a major impact on the risk of breast cancer.

The epidemiology of soft tissue sarcoma.

Soft tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed annually in the United States. Population-based data from Connecticut covering the years 1935-1989 have shown an increasing incidence of STS in both genders, with a greater increase among men than women. The recent increase in acquired immune deficiency syndrome-related Kaposi's sarcoma does not explain the upward trend in STS, dating back decades. Etiologic heterogeneity is suggested by epidemiologic variations that have been observed by subsite and cell type. Among the environmental factors associated with STS are external radiation therapy, Thorotrast, arsenical pesticides and medications, phenoxyherbicides, dioxin, vinyl chloride, immunosuppressive drugs, alkylating agents, androgen-anabolic steroids, human immunodeficiency virus, and human herpes virus type 8. In addition, STS occurs excessively among persons with certain heritable states including retinoblastoma, Li-Fraumeni syndrome, Gardner's syndrome, Werner's syndrome, nevoid basal cell carcinoma syndrome, neurofibromatosis type 1, and some immunodeficiency syndromes. These risk factors account for a minority of STS cases but provide leads for further epidemiologic and interdisciplinary studies into the genetic and environmental determinants of various forms of STS.

Agricultural exposures and cancer.

The purpose of this report is to review the literature on cancer among persons employed in agriculture, to characterize the value of this line of research, and to recommend future directions. Farmers, despite a generally favorable mortality, appear to experience elevated rates for several cancers, including leukemia, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the skin, lip, stomach, brain, and prostate. The rates for several of these tumors (i.e., non-Hodgkin's lymphoma, multiple myeloma, skin, brain, and prostate) appear to be increasing in the general population. No set of established etiologic factors explains all the cancer excesses observed among farmers, although several are associated with naturally occurring or medically induced immunodeficiencies. This suggests that there may be factors in the agricultural environment that introduce immune system deficiencies. Farmers are exposed to a variety of substances that could operate through this mechanism, including pesticides, engine exhausts, solvents, dusts, and zoonotic microbes. Studies to further characterize the cancer risk among farmers, their dependents, and farm laborers, and to identify the exposures that may be involved would not only be useful in providing a safe work environment in agriculture but may furnish considerable insight into the causes for a number of tumors that are rising in incidence in the general population.

Nonhormonal drugs and cancer.

Nonhormonal drugs probably account for only a small proportion of human cancer but have contributed many valuable insights into carcinogenic mechanisms. The antineoplastics, radiopharmaceuticals, and a few other agents account for most of the known drug-induced cancer. A number of other agents are under suspicion, usually due to studies in laboratory animals or to preliminary clinical or epidemiologic observations. This group includes some drugs in widespread use such as clofibrate and cimetidine. For a few drugs that are carcinogenic in animals, such as dapsone and isoniazid, epidemiologic studies have shown little to no evidence of carcinogenicity. Recent experimental studies have shown tumor promotion by the commonly used antidepressants amitriptyline and fluoxetine and some antihistamines, which deserve epidemiologic investigation of cancer risk. Some drugs may also protect against cancer, as suggested by the lower risk of colorectal cancer among regular users of nonsteroidal antiinflammatory drugs. Pharmacoepidemiologic studies must take into account possible confounding by the original conditions for which drugs were taken and the typically long latency period of drug-induced cancer. Improved postmarketing surveillance, continued routine case-control surveillance, and ad hoc case-control and cohort studies are needed to evaluate drugs already in use as well as newly introduced agents.

Racial, ethnic, and gender variations in cancer risk: considerations for future epidemiologic research.

There is no question that the risk of many cancers varies substantially by race, ethnic group, and gender. Although important clues to cancer etiology may come from investigating the differences in risk across subgroups of the population, epidemiologic research has often focused on white men. More descriptive and analytic studies are needed to identify and explain variations in risk among population subgroups. Especially important are studies to clarify the role of differential exposures, susceptibility, and diagnostic factors in cancer incidence, although differences in treatment may contribute to variations in cancer mortality. Improvements in classification of ethnicity, assessment of carcinogenic exposures in various subpopulations, and measures of host susceptibility states should augment future epidemiologic research designed to better understand mechanisms underlying the racial, ethnic, and gender differences in cancer risk.

Childhood cancer: overview of incidence trends and environmental carcinogens.

An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively. From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia, gliomas, and, to a much lesser extent, Wilms' tumor. There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol. Many other agents such as electromagnetic fields, pesticides, and some parental occupational exposures are suspected of playing roles, but the evidence is not conclusive at this time. Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood. For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults.

Pesticides and childhood cancer.

Children are exposed to potentially carcinogenic pesticides from use in homes, schools, other buildings, lawns and gardens, through food and contaminated drinking water, from agricultural application drift, overspray, or off-gassing, and from carry-home exposure of parents occupationally exposed to pesticides. Parental exposure during the child's gestation or even preconception may also be important. Malignancies linked to pesticides in case reports or case-control studies include leukemia, neuroblastoma, Wilms' tumor, soft-tissue sarcoma, Ewing's sarcoma, non-Hodgkin's lymphoma, and cancers of the brain, colorectum, and testes. Although these studies have been limited by nonspecific pesticide exposure information, small numbers of exposed subjects, and the potential for case-response bias, it is noteworthy that many of the reported increased risks are of greater magnitude than those observed in studies of pesticide-exposed adults, suggesting that children may be particularly sensitive to the carcinogenic effects of pesticides. Future research should include improved exposure assessment, evaluation of risk by age at exposure, and investigation of possible genetic-environment interactions. There is potential to prevent at least some childhood cancer by reducing or eliminating pesticide exposure.

Differences in cancer incidence, mortality, and survival between African Americans and whites.

This report highlights selected evidence of different cancer patterns among African Americans and whites and considers potential risk factors associated with these cancers. During the years 1987 to 1991, African Americans experienced higher incidence and mortality rates than whites for multiple myeloma and for cancers of the oropharynx, colorectum, lung and bronchus, cervix, and prostate. African Americans had lower incidence and mortality for cancer of the urinary bladder. The incidence of breast cancer was higher among white women, but mortality was higher among African American women. Five-year relative survival for the period 1983 to 1990 was generally lower among African Americans than whites for cancers of the oropharynx, colorectum, cervix, prostate, and female breast but slightly higher for multiple myeloma. From 1973 to 1991, there were significant declines in cervical cancer incidence among women of both races, oropharyngeal cancer mortality among whites, and bladder cancer mortality for whites and African Americans. Risk factors for the more prominent cancers suggest that efforts aimed at changing lifestyles, achieving socioeconomic parity, and insuring environmental equity are likely to relieve African Americans of much of their disproportionate cancer burden.

Cancer mortality and environmental exposure to DDE in the United States.

To explore the role of DDE, the major and most persistent DDT derivative, in cancer etiology, we examined the association of the 1968 adipose DDE levels of population samples from 22 U.S. states with age-adjusted mortality rates between 1975 and 1994 for multiple myeloma; non-Hodgkin lymphoma (NHL); and cancer of the breast, corpus uteri, liver, and pancreas. Separate analyses were conducted by gender and race. Covariates in the regression models included average per-capita income, percent metropolitan residents, and the population density. Liver cancer mortality increased significantly with adipose DDE levels in both sexes among whites, but not among African Americans. No association was observed for pancreatic cancer and multiple myeloma. Breast cancer mortality was inversely correlated with adipose DDE levels among both white and African American women. Significant inverse correlations were also observed for uterine cancer among white women, whereas no association was observed for African Americans and for NHL among whites (men and women) and African American women. The results for pancreatic cancer, multiple myeloma, NHL, breast cancer, and uterine cancer did not support the hypothesis of an association with past adipose levels of the DDT derivative DDE. The multivariate analysis confirmed most findings. The association between liver cancer and DDE observed among whites, particularly in view of the occurrence of hepatic neoplasms in laboratory animals exposed to DDT, warrants further investigation.

Factors associated with self-reported, pesticide-related visits to health care providers in the agricultural health study.

To investigate factors associated with pesticide-related visits to health care providers (i.e., doctor or hospital visits), responses to self-administered questionnaires received from 35,879 licensed restricted-use pesticide applicators participating in the Agricultural Health Study were analyzed. (In Iowa, applicators are actually certified, whereas in North Carolina they are licensed; for ease of reference, the term license will be used for both states in this paper.) The cohort reported a total of more than 10.9 million pesticide-application days. These applications were associated with one or more pesticide-related health care visits by 2,214 applicators (7.0% of the applicator cohort for whom health care visit data were available). The odds of a pesticide-related health care visit were increased for commercial applicators compared to private applicators [odds ratio (OR = 1.77; 95% confidence interval (CI), 1.52-2.06) and for applicators who used insecticides 70 times or more in their lifetime compared to those who used insecticides less frequently (OR = 1.43; CI, 1.26-1.63). After adjusting for the number of applications in a logistic regression model, significantly higher odds of health care visits were observed among North Carolina applicators compared to Iowa applicators (OR = 1.35; CI, 1.17-1.52), among applicators who mixed their own pesticides (OR = 1.65; CI, 1. 22-2.23), and among applicators who personally repaired their pesticide application equipment at least once per year (OR = 1.12; CI, 1.06-1.25). Significantly lower odds were found among female versus male applicators (OR = 0.68; CI, 0.46-0.99) and among applicators who graduated from high school versus those who did not (OR = 0.82; CI, 0.71-0.94 for high school graduates and OR = 0.79; CI, 0.68-0.91 for those with at least some college). Several methods of pesticide application to crops, seed, or stored grain were also associated with significantly elevated odds ratios of health care visits. These observations suggest that several steps can be taken to reduce the number of health care visits resulting from occupational exposure to pesticides. The implications of this pattern of pesticide-related health care visits may have etiologic implications for cancer and other chronic diseases.

The Agricultural Health Study.

The Agricultural Health Study, a large prospective cohort study has been initiated in North Carolina and Iowa. The objectives of this study are to: 1) identify and quantify cancer risks among men, women, whites, and minorities associated with direct exposure to pesticides and other agricultural agents; 2) evaluate noncancer health risks including neurotoxicity reproductive effects, immunologic effects, nonmalignant respiratory disease, kidney disease, and growth and development among children; 3) evaluate disease risks among spouses and children of farmers that may arise from direct contact with pesticides and agricultural chemicals used in the home lawns and gardens, and from indirect contact, such as spray drift, laundering work clothes, or contaminated food or water; 4) assess current and past occupational and nonoccupational agricultural exposures using periodic interviews and environmental and biologic monitoring; 5) study the relationship between agricultural exposures, biomarkers of exposure, biologic effect, and genetic susceptibility factors relevant to carcinogenesis; and 6) identify and quantify cancer and other disease risks associated with lifestyle factors such as diet, cooking practices, physical activity, smoking and alcohol consumption, and hair dye use. In the first year of a 3-year enrollment period, 26,235 people have been enrolled in the study, including 19,776 registered pesticide applicators and 6,459 spouses of registered farmer applicators. It is estimated that when the total cohort is assembled in 1997 it will include approximately 75,000 adult study subjects. Farmers, the largest group of registered pesticide applicators comprise 77% of the target population enrolled in the study. This experience compares favorably with enrollment rates of previous prospective studies.

Joint effects of nine polychlorinated biphenyl (PCB) congeners on breast cancer risk.

BACKGROUND: Polychlorinated biphenyls (PCB) have been a major environmental health concern because of their wide distribution and persistence in the environment. Estimating joint effects of all congeners in a single analysis is complicated by correlation among exposure levels, and the resulting collinearity makes the results difficult to interpret. METHODS: Patients with breast-related surgery at Yale-New Haven Hospital were interviewed using a standardized questionnaire, and breast adipose tissue samples were analysed for nine PCB congeners (74, 118, 138, 153, 156, 170, 180, 183, 187). The study recruited 490 women (304 cases and 186 controls) between 1994 and 1997. Logistic ridge regression was used to analyse the instability caused by collinearity. RESULTS: Although total PCB did not appear to be associated with breast cancer risk, significant differences in effect were observed among the nine congeners. Logistic ridge regression demonstrated a protective effect on breast cancer risk for a potentially anti-oestrogenic and dioxin-like congener, 156, while two phenobarbital, CYP1A and CYP2B inducers had an adverse effect, 180 and 183. This analysis also suggested that a protective effect for another phenobarbital congener, 153, was largely explained by instability caused by collinearity. CONCLUSIONS: These results indicate that studies of PCB congeners and health require an in-depth statistical analysis in order to better understand the complex issues related to their collinearity.