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Ernst Wynder published nearly 800 papers during his lifetime. I used the ISI Web of Science to analyze his publications and the subsequent literature citing his work. More than half of his papers were published in just ten journals, including Cancer, Preventive Medicine (which he founded and edited), JNCI, and Cancer Research. The 87 papers in Cancer covered all of the major cancer sites including breast, colon, lung, and prostate, and many others. Twenty-five papers and one book were cited in over 200 publications. His publications included 441 co-authors from a broad range of scientific disciplines.

Objectives: We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case-control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model., Methods: Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects' homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH-DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station., Results: The data for soil, PAH-DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40-80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection.

The detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human lymphocytes may be useful as a surrogate end point for individual cancer risk prediction. In this study, we examined the relationship between environmental sources of residential PAH, as well as other potential factors that may confound their association with cancer risk, and the detection of PAH-DNA adducts in a large population-based sample of adult women. Adult female residents of Long Island, New York, aged at least 20 years were identified from the general population between August 1996 and July 1997. Among 1556 women who completed a structured questionnaire, 941 donated sufficient blood (25+ ml) to allow use of a competitive ELISA for measurement of PAH-DNA adducts in peripheral blood mononuclear cells. Ambient PAH exposure at the current residence was estimated using geographic modeling (n=796). Environmental home samples of dust (n=356) and soil (n=360) were collected on a random subset of long-term residents (15+ years). Multivariable regression was conducted to obtain the best-fitting predictive models. Three separate models were constructed based on data from : (A) the questionnaire, including a dietary history; (B) environmental home samples; and (C) geographic modeling. Women who donated blood in summer and fall had increased odds of detectable PAH-DNA adducts (OR=2.65, 95% confidence interval (CI)=1.69, 4.17; OR=1.59, 95% CI=1.08, 2.32, respectively), as did current and past smokers (OR=1.50, 95% CI=1.00, 2.24; OR=1.46, 95% CI=1.05, 2.02, respectively). There were inconsistent associations between detectable PAH-DNA adducts and other known sources of residential PAH, such as grilled and smoked foods, or a summary measure of total dietary benzo-[a]-pyrene (BaP) intake during the year prior to the interview. Detectable PAH-DNA adducts were inversely associated with increased BaP levels in dust in the home, but positively associated with BaP levels in soil outside of the home, although CIs were wide. Ambient BaP estimates from the geographic model were not associated with detectable PAH-DNA adducts. These data suggest that PAH-DNA adducts detected in a population-based sample of adult women with ambient exposure levels reflect some key residential PAH exposure sources assessed in this study, such as cigarette smoking.

The lung cancer mortality rate has been lower in Japan than in the United States for several decades. We hypothesized that this difference is due to the Japanese preference for cigarettes with charcoal-containing filters, which efficiently absorb selected gas phase components of mainstream smoke including the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. We analyzed a subset of smokers (396 cases and 545 controls) from a case-control study of lung cancer conducted in Aichi Prefecture, Japan. The risk associated with charcoal filters (73% of all subjects) was evaluated after adjusting for age, sex, education and smoking dose. The odds ratio (OR) associated with charcoal compared with 'plain' cigarette filters was 1.2 (95% confidence intervals [CI] 0.9, 1.6). The histologic-specific risks were similar (e.g. OR = 1.3, 95% CI 0.9, 2.1 for adenocarcinoma). The OR was 1.7 (95% CI 1.1, 2.9) in smokers who switched from 'plain' to charcoal brands. The mean daily number of cigarettes smoked in subjects who switched from 'plain' to charcoal brands was 22.5 and 23.0, respectively. The findings from this study did not indicate that charcoal filters were associated with an attenuated risk of lung cancer. As the detection of a modest benefit or risk (e.g. 10-20%) that can have significant public health impact requires large samples, the findings should be confirmed or refuted in larger studies.

Background: In the United States, Blacks who smoke cigarettes have a higher mean blood concentration of the nicotine metabolite cotinine than White smokers. It has not been determined whether there are racial differences in the exposure to the cigarette smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and in the detoxification of NNK metabolites., Methods: A community-based cross-sectional survey of 69 Black and 93 White smokers was conducted in lower Westchester County, New York. Information on smoking and lifestyle habits was collected and urinary concentrations of several tobacco smoke biomarkers were compared, including the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). A frequency histogram and probit plot of NNAL-Gluc:NNAL ratios were constructed to determine slow and rapid glucuronidation phenotypes., Results: The mean concentrations of total NNAL, urinary cotinine, plasma cotinine, and thiocyanate were significantly higher in Black men than in White men for each cigarette smoked. In women, the only biomarker that was significantly elevated in Blacks was plasma cotinine. A higher proportion of White versus Black women was categorized as "rapid" glucuronidators (two-tailed exact test, P = 0.03). In men, there were no significant differences in NNAL-Gluc:NNAL phenotypes., Conclusions: The higher rates of lung carcinoma in black men may be due in part to a higher level of exposure to tobacco smoke carcinogens., (Copyright 2005 American Cancer Society.)

Objectives: Adenocarcinoma has replaced squamous cell carcinoma as the most common cell type of lung cancer in the United States. It has been proposed that this shift is due to the increased use of filter and lower-tar cigarettes, resulting in increased delivery of smoke to peripheral regions of the lungs, where adenocarcinoma usually occurs. We reviewed radiologic data to evaluate the hypothesis that tumors in smokers of cigarettes with lower-tar yield are more likely to occur peripherally than tumors in smokers of higher-yield cigarettes., Methods: At two urban academic medical centers, we reviewed computed tomographic scans, chest radiographs, and medical records to assign tumor location (peripheral or central) for 330 smokers diagnosed with carcinoma of the lung between 1993 and 1999. We compared the proportion of tumors in a peripheral versus central location by lifetime filter use and average lifetime tar rating (< 21 and > or = 21 mg)., Results: Tumor location (69% peripheral and 31% central) was unrelated to cigarette filter use. Smokers of cigarettes with lower-tar ratings were more likely than those with higher ratings to have peripheral rather than central tumors (odds ratio, 1.76; 95% confidence interval, 0.89-3.47). When restricted to subjects with adenocarcinoma or squamous cell carcinoma, the odds ratio (95% confidence interval) was 2.31 (1.05-5.08)., Conclusions: Among cigarette smokers with lung cancer, use of cigarettes with lower-tar yield was associated with preferential occurrence of tumors in peripheral sites. Our findings support the hypothesis that changes in smoking associated with lower-tar cigarettes have led to a shift in the location of smoking-related lung cancer.

Background: The Barclay cigarette (Brown & Williamson) was introduced in 1980 in the USA in the most expensive launch in history. In the USA and around the world, Barclay was later determined to have a grooved filter design that was compromised by human smokers in the normal act of smoking, but that was measured as ultra-low tar using the standard tar testing protocol., Objectives: To evaluate whether Brown & Williamson knew of the compensatability of Barclay during the design process and before it was released; to evaluate initial responses of competing tobacco companies to Barclay, before complaints were made to the Federal Trade Commission in 1981., Methods: Internet databases of industry documents (Tobacco Documents Online, Legacy Tobacco Documents Library, Brown & Williamson Litigation discovery website, Guildford and major company websites) were searched using key words, key dates, and targeted searches. Documents related specifically to the development, evaluation and release of the Barclay cigarette and related to the responses by competing tobacco companies were examined., Results: Documents indicate the manufacturer was aware of Barclay design problems and was planning, before release, to respond to criticism. Competing companies quickly detected the filter groove stratagem and considered developing their own similar filter, but eventually backed off., Conclusion: The design problems with Barclay were readily understood by cigarette manufacturers, including the maker of Barclay, before official governmental evaluations occurred. Testing involving measured exposures to human smokers may in the end be crucial to identifying problems with novel cigarette designs.

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer in several small studies. The authors' pooled analysis included 873 cases and 941 controls from a population-based case-control study. Competitive enzyme-linked immunosorbent assay in peripheral mononuclear cells was conducted in 2 rounds, and results were pooled on the basis of round-specific quantiles. The odds ratio for breast cancer was elevated in relation to detectable PAH-DNA adducts (1.29 as compared with nondetectable adduct levels; 95% confidence interval = 1.05, 1.58), but there was no apparent dose-response relationship with increasing quantiles. No consistent pattern emerged when the results were stratified by PAH sources (e.g., active cigarette smoking or PAH-containing foods), or when the cases were categorized by stage of disease or hormone receptor status. These data provide only modest support for an association between PAH-DNA adducts and breast cancer development.

Nearly 19.5 million gallons of herbicides were sprayed on the Republic of Vietnam between 1961 and 1971 for military purposes. Amounts of spray and patterns of applications are available in an electronic file called HERBS that contains records of 9141 defoliation missions, including detailed coordinates of US Air Force Ranch Hand aircraft flight paths, along with chemical agent and gallonage sprayed. Two classes of models for use in epidemiological and environmental studies that utilize the HERBS data for estimating relative exposure opportunity indices are presented: a discrete "hits" model that counts instances of proximity in time and space to known herbicide applications, and a continuous exposure opportunity index, E4, that takes into account type and amount of herbicide sprayed, distance from spray application, and time interval when exposure may have occurred. Both direct spraying and indirect exposure to herbicide (or dioxin) that may have remained in the local environment are considered, using a conservative first-order model for environmental disappearance. A correction factor for dermal versus respiratory routes of entry has been incorporated. E4 has a log-normal distribution that spans six orders of magnitude, thus providing a substantial amount of discrimination between sprayed and unsprayed areas. The models improve on earlier ones by making full use of the geometry of the HERBS spray flight paths of Ranch Hand aircraft. To the extent possible so many decades after the War, the models have been qualitatively validated by comparison with recent dioxin soil and biota samples from heavily contaminated areas of Vietnam, and quantitatively validated against adipose dioxin obtained in epidemiological studies of Vietnamese. These models are incorporated within a geographic information system (GIS) that may be used, as one would expect, to identify locations such as hamlets, villages, and military installations sprayed by herbicide. In a novel application, the GIS also facilitates quantitative risk assessment in epidemiological and ecological studies by applying the models within a framework of historical reconstruction of exposure history of individuals based upon their location histories.

Risk factors affecting the course of posttraumatic stress disorder (PTSD) are poorly understood. As part of a larger study on characterizing exposure to herbicides in Vietnam, the authors investigated this issue in a random sample of 1,377 American Legionnaires who had served in Southeast Asia during the Vietnam War and were followed over a 14-year period. High combat exposure, perceived negative community attitudes at homecoming, minority race, depression symptoms at Time 1, and more anger at Time 1 predicted a more chronic course. Community involvement at Time 1 was protective and associated with decreased risk at Time 2. Discomfort in disclosing Vietnam experiences was associated with an increased risk for developing PTSD but did not predict its course. Combat exposure predicted PTSD course more strongly than any other risk factor. Findings suggest recovery from PTSD is significantly influenced by perceived social support., ((c) 2003 APA)

Several studies have measured the association between blood or adipose concentrations of organochlorinated compounds (OCs), such as pesticides and polychlorinated biphenyls (PCBs), and breast cancer. The estrogenic effects of OCs might adversely affect breast cancer recurrence. The participants were 224 women with nonmetastatic breast cancer enrolled in a New York-based case-control study. Supercritical fluid extraction followed by gas chromatography was conducted on adipose surgical specimens to determine OC concentrations. The mean follow-up time from surgery was 3.6 years. Thirty women (13.4%) were diagnosed with a recurrence. The concentration of pesticides and PCBs was correlated with baseline age and body mass index, but not with cancer stage. The highest tertile of total PCB concentration was associated with an increased risk of recurrence [relative risk (RR), 2.9; 95% confidence interval (CI), 1.02-8.2 versus the lowest tertile]. The risk for the highest tertile of the PCB congener Ballschmiter and Zell 118 was 4.0 (95% CI, 1.3-4.9). There was an increased risk for the middle level of the most abundant pesticide, 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene (RR, 2.3; 95% CI, 0.9-5.7), and for beta-hexachlorocyclohexane, but not for their highest levels. Self-reported home termiticide exposure, alcohol consumption (> or = 1 drink/day), and race were not associated with prognosis. The RR for current cigarette smoking at diagnosis was 2.1 (95% CI, 0.9-5.1). In contrast to previous data showing no relationship between OC exposure and risk of breast cancer in these women, adipose PCB concentrations were associated with tumor recurrence. Pesticide levels were not related to recurrence.

Herbicides including Agent Orange were sprayed by United States forces for military purposes during the Vietnam War (1961-1971) at a rate more than an order of magnitude greater than for similar domestic weed control. In 1974, the US National Academy of Sciences published estimates of the extent and distribution of herbicides sprayed. Here we present revised estimates, developed using more-complete data. The spray inventory is expanded by more than seven million litres, in particular with heavily dioxin-contaminated herbicides. Estimates for the amount of dioxin sprayed are almost doubled. Hamlet census data reveal that millions of Vietnamese were likely to have been sprayed upon directly. Our identification of specific military herbicide targets has led to a more coherent understanding of spraying. Common errors in earlier interpretations of the spray data are also discussed.

Background: Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit the development of lung tumors in experimental animals. To the authors' knowledge there are little data regarding whether regular use of NSAIDs reduces the risk of developing lung carcinoma in humans., Methods: The association between lung carcinoma risk and regular use of NSAIDs, including aspirin, was evaluated in a hospital-based case-control study of 1038 patients and 1002 controls., Results: The relative risk estimate of lung carcinoma associated with using NSAIDs 3 times a week or more for 1 or more years demonstrated an odds ratio (OR) of 0.68 (95% confidence interval [95% CI], 0.53-0.89). Results were similar when separated by lung histologic type. The association varied by smoking status. The OR was 1.28 (95% CI, 0.73-2.25) in never-smokers and 0.60 (95% CI 0.45-0.80) in ever-smokers. The smoking-specific risk estimates for aspirin were similar to those for all NSAIDs., Conclusions: The results of the current study suggest a possible chemoprotective benefit with the use of NSAIDs among individuals who are former or current smokers., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11242)

Between 1961 and 1971, U.S. military forces dispersed more than 19 million gallons of phenoxy and other herbicidal agents in the Republic of Vietnam, including more than 12 million gallons of dioxin-contaminated Agent Orange, yet only comparatively limited epidemiologic and environmental research has been carried out on the distribution and health effects of this contamination. As part of a response to a National Academy of Sciences' request for development of exposure methodologies for carrying out epidemiologic research, a conceptual framework for estimating exposure opportunity to herbicides and a geographic information system (GIS) have been developed. The GIS is based on a relational database system that integrates extensive data resources on dispersal of herbicides (e.g., HERBS records of Ranch Hand aircraft flight paths, gallonage, and chemical agent), locations of military units and bases, dynamic movement of combat troops in Vietnam, and locations of civilian population centers. The GIS can provide a variety of proximity counts for exposure to 9,141 herbicide application missions. In addition, the GIS can be used to generate a quantitative exposure opportunity index that accounts for quantity of herbicide sprayed, distance, and environmental decay of a toxic factor such as dioxin, and is flexible enough to permit substitution of other mathematical exposure models by the user. The GIS thus provides a basis for estimation of herbicide exposure for use in large-scale epidemiologic studies. To facilitate widespread use of the GIS, a user-friendly software package was developed to permit researchers to assign exposure opportunity indexes to troops, locations, or individuals.

Occupational epidemiology has its roots in classical medicine. However, it became a quantitative discipline only in the 20th century, through the pioneering work of individuals such as Case, Lloyd, and Selikoff and organizations such as the Division of Occupational Health of the U.S. Public Health Service. Studies of chemical dye workers, bituminous coal miners, smelting workers, and uranium miners have been especially important sources of innovations in methodology and in development of logical reasoning leading to acceptance of causal relationships of occupational exposures that lead to respiratory diseases and cancer. The cooperation of labor unions, such as those of steel and asbestos workers, has often been a crucial factor in providing essential data.

Objective: To determine if cigarette mentholation is associated with the frequency of smoking and with quitting, and whether mentholation explains racial differences in these two smoking behaviours., Design: Cross sectional analysis of case-control data on smoking and lung cancer., Subjects: Limited to 19 545 current and former cigarette smokers., Main Outcome Measures: Smoking > 20 cigarettes per day (cpd) versus < or = 20 cpd, and continued smoking versus quit smoking., Results: Among blacks, the prevalence odds ratio (POR) of heavy smoking (> or = 21 cpd) associated with mentholated cigarettes versus non-mentholated cigarettes was 0.7 (95% confidence interval (CI) 0.5 to 0.9) in current smokers and 0.6 (95% CI 0.4 to 0.9) in former smokers. Among whites, the corresponding POR were 0.9 (95% CI 0.8 to 1.0) and 0.9 (95% CI 0.8 to 1.0). Blacks were less likely to have been heavy smokers than whites, but the difference was unrelated to cigarette mentholation. The POR of continued smoking versus quitting, associated with mentholated cigarettes was 1.1 (95% CI 1.0 to 1.2) for both blacks and whites., Conclusion: Smoking > 20 cpd was independently associated with white race. Among blacks, smoking < or = 20 cpd was independently associated with mentholated cigarettes. The risk of quitting was not associated with cigarette menthol flavour.

Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effect on breast cancer development in women is not clear. To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. Cases were women newly diagnosed with in situ and invasive breast cancer; controls were randomly selected women frequency matched to the age distribution of cases. Blood samples were donated by 1102 (73.0%) and 1141 (73.3%) of case and control respondents, respectively. Samples from 576 cases and 427 controls were assayed for PAH-DNA adducts using an ELISA. The geometric mean (and geometric SD) of the log-transformed levels of PAH-DNA adducts on a natural scale was slightly, but nonsignificantly, higher among cases [7.36 (7.29)] than among controls [6.21 (4.17); P = 0.51]. The age-adjusted odds ratio (OR) for breast cancer in relation to the highest quintile of adduct levels compared with the lowest was 1.51 [95% confidence interval (CI), 1.04-2.20], with little or no evidence of substantial confounding (corresponding multivariate-adjusted OR, 1.49; 95% CI, 1.00-2.21). There was no consistent elevation in risk with increasing adduct levels, nor was there a consistent association between adduct levels and two of the main sources of PAH, active or passive cigarette smoking or consumption of grilled and smoked foods. These data indicate that PAH-DNA adduct formation may influence breast cancer development, although the association does not appear to be dose dependent and may have a threshold effect.

Whether environmental contaminants increase breast cancer risk among women on Long Island, NY, is unknown. The study objective is to determine whether breast cancer risk is increased in relation to organochlorines, compounds with known estrogenic characteristics that were extensively used on Long Island and other areas of the United States. Recent reports do not support a strong association, although there are concerns with high risks observed in subgroups of women. Blood samples from 646 case and 429 control women from a population-based case-control study conducted on Long Island were analyzed. No substantial elevation in breast cancer risk was observed in relation to the highest quintile of lipid-adjusted serum levels of p,p'-bis(4-chlorophenyl)-1,1-dichloroethene (DDE) [odds ratio (OR), 1.20 versus lowest quintile; 95% confidence interval (CI), 0.76-1.90], chlordane (OR, 0.98; 95% CI, 0.62-1.55), dieldrin (OR, 1.37; 95% CI, 0.69-2.72), the sum of the four most frequently occurring PCB congeners (nos. 118, 153, 138, and 180; OR, 0.83; 95% CI, 0.54-1.29), and other PCB congener groupings. No dose-response relations were apparent. Nor was risk increased in relation to organochlorines among women who had not breastfed or were overweight, postmenopausal, or long-term residents of Long Island; or with whether the case was diagnosed with invasive rather than in situ disease, or with a hormone receptor-positive tumor. These findings, based on the largest number of samples analyzed to date among primarily white women, do not support the hypothesis that organochlorines increase breast cancer risk among Long Island women.

The Long Island Breast Cancer Study Project is a federally mandated, population-based case-control study to determine whether breast cancer risk among women in the counties of Nassau and Suffolk, NY, is associated with selected environmental exposures, assessed by blood samples, self-reports, and environmental home samples. This report describes the collaborative project's background, rationale, methods, participation rates, and distributions of known risk factors for breast cancer by case-control status, by blood donation, and by availability of environmental home samples. Interview response rates among eligible cases and controls were 82.1% (n = 1,508) and 62.8% (n = 1,556), respectively. Among case and control respondents who completed the interviewer-administered questionnaire, 98.2 and 97.6% self-completed the food frequency questionnaire; 73.0 and 73.3% donated a blood sample; and 93.0 and 83.3% donated a urine sample. Among a random sample of case and control respondents who are long-term residents, samples of dust (83.6 and 83.0%); soil (93.5 and 89.7%); and water (94.3 and 93.9%) were collected. Established risk factors for breast cancer that were found to increase risk among Long Island women include lower parity, late age at first birth, little or no breast feeding, and family history of breast cancer. Factors that were found to be associated with a decreased likelihood that a respondent would donate blood include increasing age and past smoking; factors associated with an increased probability include white or other race, alcohol use, ever breastfed, ever use of hormone replacement therapy, ever use of oral contraceptives, and ever had a mammogram. Long-term residents (defined as 15+ years in the interview home) with environmental home samples did not differ from other long-term residents, although there were a number of differences in risk factor distributions between long-term residents and other participants, as anticipated.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was >10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Context: A relative paucity of data exist on the possible health effects of using cellular telephones., Objective: To test the hypothesis that using handheld cellular telephones is related to the risk of primary brain cancer., Design and Setting: Case-control study conducted in 5 US academic medical centers between 1994 and 1998 using a structured questionnaire., Patients: A total of 469 men and women aged 18 to 80 years with primary brain cancer and 422 matched controls without brain cancer., Main Outcome Measure: Risk of brain cancer compared by use of handheld cellular telephones, in hours per month and years of use., Results: The median monthly hours of use were 2.5 for cases and 2.2 for controls. Compared with patients who never used handheld cellular telephones, the multivariate odds ratio (OR) associated with regular past or current use was 0.85 (95% confidence interval [CI], 0.6-1.2). The OR for infrequent users (<0. 72 h/mo) was 1.0 (95% CI, 0.5-2.0) and for frequent users (>10.1 h/mo) was 0.7 (95% CI, 0.3-1.4). The mean duration of use was 2.8 years for cases and 2.7 years for controls; no association with brain cancer was observed according to duration of use (P =.54). In cases, cerebral tumors occurred more frequently on the same side of the head where cellular telephones had been used (26 vs 15 cases; P =.06), but in the cases with temporal lobe cancer a greater proportion of tumors occurred in the contralateral than ipsilateral side (9 vs 5 cases; P =.33). The OR was less than 1.0 for all histologic categories of brain cancer except for uncommon neuroepitheliomatous cancers (OR, 2.1; 95% CI, 0.9-4.7)., Conclusions: Our data suggest that use of handheld cellular telephones is not associated with risk of brain cancer, but further studies are needed to account for longer induction periods, especially for slow-growing tumors with neuronal features.

To assess a possible etiological role of organochlorine compounds in breast cancer development on Long Island, a high-risk region of New York State, concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were measured in the adipose tissue of 232 women with breast cancer and 323 hospital controls admitted to surgery for benign breast disease or non-breast-related conditions. Seven pesticide residues and 14 PCB congeners were assayed via a supercritical fluid extraction method followed by gas chromatography with electron capture detection. After adjustment for age and body mass index, which were strongly correlated with organochlorine levels, adipose concentrations of 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, and total polychlorinated biphenyls (PCBs) did not differ significantly between cases and controls. The relative abundance of individual pesticide species and PCB congeners was similar in cases and controls. Odds ratios adjusted for age, BMI, hospital, and race gave no evidence of a dose-response for 1,1-dichloro-2,2-di(4-chlorophenyl)ethylene, total pesticides, or total PCBs, whether stratified by estrogen receptor status or not. Breast cancer risk among Long Island residents was not elevated compared with residents of the adjacent New York City borough of Queens. We did not confirm a previously reported association between breast cancer risk and levels of PCB congener 118 (2,3',4,4',5-pentachlorobiphenyl), nor did we observe an association with the most abundant congener 153 (2,2',4,4',5,5'-hexachlorobiphenyl), a strong inducer of phase I enzymes that was reported recently to have estrogenic properties. Only PCB congener 183 (2,2',3,4,4',5',6-heptachlorobiphenyl), which is also an inducer, was significantly associated with risk, with an adjusted odds ratio of 2.0 (95% confidence interval, 1.2-3.4) in women with adipose levels >5.67 ng/g; the biological importance of this observation is unclear without confirmation in additional studies. Although neither the present nor other studies have provided convincing evidence of an association between body burden of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane and PCBs with cancer of the breast, these compounds are rated as "possible" and "probable" human carcinogens, respectively, by the International Agency for Research on Cancer. Investigations of associations with cancer at other sites should be carried out.

O6-Alkylguanine DNA alkyltransferase (AGT) plays an important role in the repair of alkylating agent-induced DNA damage and protection from the carcinogenic effects of environmental agents. To examine the importance of the AGT codon 143 and codon 160 polymorphisms in risk for lung cancer and to assess the prevalence of these polymorphisms in different racial groups, we performed genotype analysis of lung cancer patients and matched controls. The prevalence of the AGT143Val allele in controls was 0.07 in Caucasians and 0.03 in African Americans. The AGT143Val allele was not detected in an unmatched Asian control cohort. The prevalence of the AGT160Arg variant allele was 0.01 in Caucasians, 0.02 in African Americans, and 0.03 in Asians. A marginally significant association was observed between the AGT codon 143 (isoleucine/valine) genotype and risk for lung cancer (odds ratio = 2.1; 95% confidence interval = 1.01-4.7). The prevalence of the AGT160Arg variant allele was similar in lung cancer cases versus matched controls. These results suggest that the AGT codon 143 polymorphism may play an important role in risk for lung cancer.

Background: Cigarette smoke yields of tar and nicotine obtained under the Federal Trade Commission (FTC)-specified machine-smoking protocol (35-mL puff volume drawn for 2 seconds once per minute) may not accurately reflect the delivery of toxins and carcinogens to the smoker. We conducted this study to obtain more realistic estimates of exposure to components of cigarette smoke that affect lung cancer risk., Methods: We used a pressure transducer system to evaluate puffing characteristics for 133 smokers of cigarettes rated by the FTC at 1.2 mg of nicotine or less (56 smokers of low-yield cigarettes [

Nonmalignant respiratory disease (NMRD) mortality was examined among woodworkers participating in the American Cancer Society's CPS-II cohort study. During the 6-year prospective follow-up there were 97 NMRD death's among 11,541 men reporting employment in wood-related occupations and 1,338 NMRD deaths among 317,424 men reporting no exposure to wood dust or wood-related jobs. Relative risks, adjusted for age and smoking, were calculated using Poisson regression. A small excess of NMRD was observed among woodworkers. However, the relative risk was higher among woodworkers who did not report exposure to wood dust (RR = 1.52, 95% CI = 1.18-1.97) than those who did (RR = 1.27, 95% CI = 0.91-1.77), and no clear trend with duration of exposure was observed. An excess of NMRD was observed among woodworkers reporting exposure to asbestos (RR = 1.59, 95% CI = 0.85-2.96), as well as the small number of woodworkers reporting exposure to formaldehyde (RR = 1.95, 95% CI = 0.63-6.06), but men not reporting exposure to these substances also had an excess risk. Although limited by a short follow-up period and crude indicators of exposure, the strengths of this analysis were the ability to compare woodworkers to a similar, healthy population and to adjust for the effects of smoking. Cohort studies with better exposure information are needed to examine the role of occupational exposures among woodworkers in the etiology of respiratory disease.

In 1994, the International Agency for Research on Cancer (IARC) classified wood duct as a human carcinogen, based on very strong evidence of a carcinogenic risk of sino-nasal cancer. Excesses of other cancers, including lung and stomach, have been reported among persons employed in wood industries or occupationally exposed to wood dust, but not as consistently. We investigated such possible associations using the mortality experience of 362,823 men enrolled in the American Cancer Society's Cancer Prevention Study-II in 1982 and followed up for 6 years. Within this group, 45,399 men (12.5%) reported either employment in a wood-related occupation or exposure to wood dust or both. Among woodworkers, a small but significant excess risk was found for all cases of death (RR 1.17 (95% CI 1.11-1.24)) and for total malignancies (RR 1.17 (1.05-1.30)). Among men who reported exposure to wood dust, there was an elevated risk of total mortality (Rr 1.07 (1.03-1.11)), total malignancies (RR 1.08 (1.01-1.15)), and lung cancer (RR 1.17 (1.04-1.31)). Among woodworkers, a significant trend (P = 0.02) of increasing risk of lung cancer with increasing duration of exposure was observed. An unexpected, significantly increased mortality from prostate cancer was observed in both wood-employed and wood-exposed, and a twofold increased risk of fatal brain cancer was seen among the former. Lung cancer mortality was especially high among woodworkers who also reported exposure to asbestos or formaldehyde, and it appears that exposure to these known carcinogens may partly explain the observed increased risks. Excess sino-nasal cancer was not observed, but the number of cases was small.

Some organochlorine pesticides (OCPs) and PCBs are under investigation as possible risk factors for breast cancer because of their estrogenic properties and widespread presence in the environment. It is important to know whether adipose tissue used by some investigators and serum assays used by others can provide comparable information on body burden. Concentrations of seven OCPs or their breakdown products as well as 14 PCB congeners were measured in the adipose tissue and serum of 293 women enrolled as controls in a case-control study of environmental factors for breast cancer in Long Island, New York, a high-risk region. Adipose OCP/PCB levels were measured using a supercritical fluid extraction method developed by the authors. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples; two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and 2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl comprised 24% of adipose and 21% of serum PCBs. The relative concentration patterns of the 14 PCB congeners were similar to those reported in other human studies and were also typical of patterns reported in environmental samples from various biota, including mammals and birds, but differed substantially from patterns reported in occupationally exposed workers. All adipose-serum correlations for pesticides and most PCBs were statistically significant. Either serum or adipose OCP/PCB levels of a variety of environmental organochlorine compounds may serve as useful biomarkers of body burden.

Agent Orange was the most common herbicide used in the Second Indochina War in the course of military operations in the former South Vietnam. Agent Orange is contaminated by the carcinogen 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in mean concentrations of 2 mg/kg. After much dispute of a causal association between exposure to herbicides containing TCDD and occurrence of soft-tissue sarcoma and non-Hodgkin lymphoma, two simultaneous case-control studies were set up in Vietnam to examine possible relationships. Subject recruitment is ongoing, with target numbers of 150 cases of soft-tissue sarcoma and 150 cases of non-Hodgkin lymphoma and diagnoses at the Cancer Center at Ho Chi Minh City, Vietnam. Two hospital controls are matched to each case. As in other studies of cancer in persons occupationally or otherwise exposed to herbicides and their contaminants, evaluation of past exposure of the recruited subjects is among the most complicated issues. Because accurate records are usually unavailable, surrogate measures of likely exposure are often calculated. As a first approach in our studies we used the Stellman and Stellman exposure index. The index is based on matching subjects' history of residence and the information on times and locations of Agent Orange spraying recorded on HERBS tape by the U.S. Army and taking into account the distance from the spraying as well as environmental and biologic half-life of TCDD. The exposure index is calculated in two centers, New York and Hanoi, with slightly different assumptions. In addition, samples of body tissues from the subjects (20 ml blood, 2 g adipose tissue, and tumor sections in paraffin blocks) are taken and stored. Their future analysis will provide additional source of exposure assessment. Strengths and weaknesses of both exposure measures are discussed in this paper.

There are little data on workplace exposures and lung cancer risk in blacks. An ongoing case-control study of lung cancer that included 550 black men and women with lung cancer and 386 age-matched controls was examined by reported occupational exposures and job titles. In men, significant associations were observed with reported exposure to asbestos [odds ratio (OR), 1.8; 95% confidence intervals (CI) 1.03-3.1] and coal dust (OR, 2.8; 95% CI 1.1-7.0). Elevated but nonsignificant risks of 1.4 or more were detected for the following occupations: police/security guards, farmers/farm workers, laborers, and motor-vehicle drivers. In women, nonsignificant increased risks were found with reported exposure to paint (OR, 1.8) and gas fumes (OR, 4.9). Women employed as farmers/farm workers and building maintenance workers had elevated but nonsignificant risks.

Background: Over the past few decades, the incidence of adenocarcinoma (AC) of the lung increased much more rapidly than that of squamous cell carcinoma (SCC) in men and women. During this time period, filter cigarettes with substantially reduced "tar" and nicotine yields in the smoke came to dominate the market., Methods: The risk of SCC and AC in lifelong smokers of filter cigarettes relative to lifelong nonfilter cigarette smokers was assessed in a case-control study performed between 1977 and 1995 with 2292 lung carcinoma patients and 1343 hospital controls who were current smokers., Results: Odds ratios (OR) for SCC in male and female subjects who had smoked filter cigarettes exclusively during their lives were slightly reduced relative to lifetime nonfilter cigarette smokers in men (OR = 0.8; 95% confidence interval [CI], 0.5-1.2), and significantly reduced in women (OR = 0.4; 95% CI, 0.2-0.8). No reduction in risk was observed for AC of the lung in men or women., Conclusions: Evidence that the increasing predominance of AC over SCC may be due in part to the reduced risk of SCC (but not AC) associated with lifelong filter cigarette smoking is strongest in women; for men, further studies that include larger numbers of lifetime filter smokers are needed to confirm this finding. A lack of protection against AC from low yield filter cigarettes may result from smokers' "compensating" with deeper and more frequent inhalation, thereby increasing delivery of carcinogens to the peripheral lung. The smoke of modern cigarettes also contains higher concentrations of nitrosamines that primarily produce AC.

Large cell carcinoma is the fourth most common histological type of lung cancer in the United States. Cigarette smoking causes large cell lung cancer, but it is uncertain whether the effect varies with the amount and duration of smoking. This uncertainty stems from ambiguity in the histopathological classification of large cell cancer, especially before 1971, and the relatively infrequent occurrence of large cell cancer in epidemiological studies. The present case-control investigation demonstrates that the risk of large cell cancer increases with both the frequency and number of years of cigarette smoking. The odds ratio associated with smoking two or more packs/day was 37.0 (95% confidence interval, 16.4-83.2) in men and 72.9 (35.4-150.2) in women. It is concluded that cigarette smoking is the predominant cause of large cell lung cancer.

Background: The rates of lung adenocarcinoma cancer have risen more rapidly than the rates of lung squamous cell cancer over the past 2 decades., Methods: A case-control study was carried out to assess the impact of long-term filter cigarette smoking on the risk of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the lung., Results: Odds ratios for SCC among subjects who had smoked only filter cigarettes were reduced relative to lifetime nonfilter cigarette smokers by 30% for men and by 60% for women, but no risk reduction was observed for AC of the lung., Conclusion: The predominance of AC over SCC may be due in part to the fact that smokers of very low yield cigarettes tend to compensate for the lower nicotine levels by inhaling more deeply and frequently, leading to greater exposure of the peripheral lung to the carcinogens in tobacco smoke, and in part to the increased concentration of nitrosamines that preferentially produce AC in laboratory animals.

Purpose: We evaluated the association between left-handedness (LH) and age, education, cigarette smoking, alcohol consumption, and disease status in a case-control study of 8801 hospitalized patients with cancer and those with other conditions., Methods: Subjects were interviewed in person using a structured questionnaire that contained detailed sections of lifestyle behaviors., Results: The overall prevalences of LH were 7.6% among men and 6.5% among women. Among both sexes LH declined with increasing age (P < 0.05). After adjustment for age, the following associations were observed. Men had a higher risk of LH than women. The prevalence of LH was lower in ever-married subjects compared with never-married subjects (odds ratio [OR] for men, 0.7; 95% confidence intervals [CI], 0.5-0.9; for women, OR, 0.5; 95% CI, 0.3-0.9). Among men, the prevalence of LH was not associated with race, years of education, smoking status, or levels of alcohol consumption. The risk of LH was elevated in men diagnosed with fractures as compared with all other male patients (OR, 2.4; 95% CI, 1.3-6.7). Among women, LH was not associated with race, smoking, or hormonal and reproductive factors, but LH was more common among female high-school and college graduates and among self-reported alcoholics. The odds ratio of LH was significantly lower in women with breast cancer (OR, 0.3; 95% CI, 0.1-0.7)., Conclusions: The increased risk of serious injuries in LH is not a result of higher alcohol use. Handedness might be an important factor in the safe use of industrial equipment.

Consumption of tobacco products, both by smoking and by other means, has long been causally connected with cancers of the lung, larynx, mouth and pharynx, oesophagus, bladder, and many other sites. Tobacco is the main specific contributor to total mortality in many developed countries and has become a major contributor in the developing countries as well. In most industrialized countries, prevalence of cigarette smoking is currently higher in low than in high social classes, although in some industrialized countries smoking was more frequent in high social classes during the first half of this century. The latter pattern of tobacco consumption is more likely to apply to developing countries. To formulate and carry out effective tobacco control activities it is essential to assess the relative incidence of tobacco-related cancers in different social strata and the prevalence of tobacco use across strata. Despite many years of data gathering the information base is far from complete, especially in developing countries where tobacco use is increasing rapidly, and where aggressive marketing by the transnational tobacco industry is occurring. A critical question is the extent to which tobacco usage can 'explain' the observed social class differences in cancer risk. Class differences in lung cancer are likely to be mostly related to the unequal distribution of tobacco smoking between social classes, and in some fairly simple situations this has been satisfactorily demonstrated. Nevertheless, there are many unresolved issues, especially with regard to the role of collateral exposures, such as hazardous occupations, poor diet, and limited access to health care. The question of whether tobacco use 'explains' socioeconomic differences in one or more of the cancers that it causes has rarely been directly addressed in epidemiological studies.

Most studies of smoking and pancreatic cancer have used male subjects or combined men and women together in statistical analyses. There is little information on the relative risk of smoking and pancreatic cancer in women. Because of the high case-fatality rate, many of these studies were also based on information gathered from proxy respondents, in which smoking habits may not be recalled with certainty. A hospital-based study of 484 male and female patients with pancreatic cancer and 954 control subjects was conducted based on direct interviews of incident cases. Compared to never smokers, the odds ratio (OR) for current cigarette smokers was 1.6 [95% confidence interval (CI), 1.1-2.4] for men and 2.3 (95% CI, 1.4-3.5) for women. In women, but not in men, there was a trend in the ORs with years of daily cigarette consumption (P < 0.01). Filter cigarettes offered no protective advantage compared to nonfilter cigarettes. Among men, the OR was 2.1 (95% CI, 1.2-3.8) for pipe/ cigar smokers and 3.6 (95% CI, 1.0-12.8) for tobacco chewers. Tobacco smoke causes pancreatic cancer when inhaled into the lungs. Tobacco juice may also cause pancreatic cancer when ingested or absorbed through the oral cavity. These data suggest that smoking is a cause of pancreatic cancer in women and that the risks for female smokers are comparable to male smokers. Nevertheless, the causes of most pancreatic cancers are unknown.

It is widely believed that the prevalence of smoking among hospital patients is greater than that of the general population because many conditions for which patients are hospitalized are caused by or associated with smoking, and that this increased prevalence may bias results of case-control studies of tobacco-related diseases. For this reason, many authors have suggested excluding from the control series patients hospitalized for tobacco-related illnesses. The present study investigated potential selection bias for hospital compared to neighborhood controls in studying tobacco-related diseases. The 709 cases from six U.S. cities had tobacco-related cancers or myocardial infarction. They were individually matched to one hospital control and to one neighbor. After excluding patients with tobacco-related diseases, hospital controls were less often current smokers and more often former smokers than neighborhood controls. Among male ever smokers, hospital controls tended to smoke more cigarettes per day than neighborhood controls. Compared with the U.S. population, there was an overrepresentation of smokers in neighborhood controls rather than an under-representation of smokers in hospital controls. Relative risk estimates varied according to type of control. Choosing between hospital and neighborhood controls in case-control studies should be dictated by criteria related to the study hypothesis, participation, or cost. In particular, exclusion of hospital controls with diseases known to be tobacco-related seems to be a successful strategy for reducing selection bias.

Objective: To assess the extent to which accuracy of death certificate completion varies with level of physician training and experience., Design and Setting: In a classroom setting, subjects were presented with six written cases of hospital deaths adapted from materials from the National Center for Health Statistics and were asked to complete the cause-of-death section of the New York City death certificate., Participants: A total of 12 practicing general internists, 21 internal medicine residents, and 35 senior medical students., Outcome Measures: The underlying cause of death recorded by each participant was compared with the correct cause determined by a nosologist. Agreement and disagreement were classified as major or minor depending on concordance within the 17 International Classification of Diseases categories., Results: Only one internist and five residents had received formal training in death certificate completion. The overall level of agreement between underlying cause of death reported by the three groups of participants and the correct cause was 56.9% for internists, 56.0% for residents, and 55.7% for medical students, although agreement varied with the type of case, ranging from 15% to 99%., Conclusion: If the misclassification observed in this pilot study were widespread, it would imply a substantial underreporting of mortality from both circulatory diseases and diabetes. These data strongly support the need to include training in death certificate completion as part of physician education.

The study of occupationally related cancers has played an important role in the control of cancer in general. The very nature of the workplace allows for studies that can help establish a relationship between an environmental exposure and cancer. Once carcinogens are identified, strategies can be developed to prevent disease. The article reviews procedures for identifying, evaluating, and categorizing human carcinogens; provides an overview of the basic epidemiologic strategies that have been used to study cancer and the workplace; and outlines the clinical evaluation of occupational exposures.

Background: About 13,000 people immigrated to New York City from the Republic of Korea between 1986 and 1990, creating an important ethnic minority., Methods: Using US-born Whites as a reference, age-adjusted proportional mortality ratios were computed for 314 men and 248 women of Korean ancestry born abroad who died in New York City in 1986-90., Results: Males had a significant excess of viral hepatitis, cancer, stroke, and external causes: accidents, suicide, and homicide. They had significantly reduced proportional rates of AIDS and heart disease. Mortality patterns were similar for Korean women, who had significantly increased proportional rates of stroke and accidents, and reduced heart disease. Stomach and liver cancers were significantly elevated in both sexes, while female breast cancer was low. There were two male and one female tuberculosis deaths (4 to 7 fold increase), and one Korean woman died of childbirth complications (59-fold increase)., Conclusions: Except for violent deaths, these observations resemble known mortality patterns in Korea.

To assess the relation between exposure to environmental tobacco smoke throughout life and lung cancer in lifetime nonsmokers, the authors conducted in-person interviews with 41 male and 69 female never-smoking lung cancer cases and 117 male and 187 female never-smoking controls between 1983 and 1990 as part of a hospital-based case-control study of tobacco-related cancers. Cases had newly diagnosed, histologically confirmed primary carcinoma of the lung. Controls were matched to cases on age (+/- 5 years), sex, race, hospital, and year of interview. Subjects were asked about environmental tobacco smoke exposure in childhood, in adulthood at home, in different jobs, and in transportation and social situations. In addition to amount smoked by family members in the subject's presence, subjects were asked to rate the intensity of each exposure, and married subjects were asked whether their spouse smoked in the bedroom. Several independent indicators of exposure to smoking by spouses were strongly correlated, thereby increasing confidence in the classification of exposure status. The reproducibility of environmental tobacco smoke variables was good for qualitative measures (yes/no), in agreement with previous studies. There were few associations of exposure in specific settings with lung cancer. Males whose wives smoked had odds ratio of 1.60 (95% confidence interval (CI) 0.67-3.82) and females whose husbands smoked had an odds ratio of 1.08 (95% CI 0.60-1.94). While this study had limited sample size, the pattern of odds ratios shows little indication of an association of environmental tobacco smoke with lung cancer in nonsmokers.

Numerous factors in the social environment may affect the incidence and mortality from cancer in women. Women's work roles, possible exposure to workplace hazards, social class, social roles, social stress, access to health care, and health behaviors are among the factors that act together to help determine a woman's health and well-being.

The association between occupational exposure to asbestos and histological type of lung cancer was analyzed in a multicenter hospital-based case-control study (2,871 male cases and 5,240 male controls) conducted from 1981-1991. Twenty-two percent of cases and 18% of controls were employed in asbestos-related occupations for at least 1 year. Most of these asbestos jobs were in the construction field. The odds ratio (OR) among current smokers was 1.0 [95% confidence intervals (CI) 0.9 to 1.3]; for ex-smokers, the OR was 1.4 (95% CI 1.1 to 1.6). In contrast, 10% of cases and 5% of controls self-reported that they were chronically exposed to asbestos for at least 1 year. Self-reported asbestos exposure was significantly related to all lung cancer cell types among smokers and ex-smokers, although a trend in the ORs with duration of self-reported exposure was not found for current smokers. Among 48 cases and 52 controls reporting distinct exposure to building insulation, the OR was 2.2 (95% CI 1.2 to 4.3) for current smokers, and 1.8 (95% CI 0.9 to 3.6) for ex-smokers, compared to subjects who were not exposed to building insulation and asbestos. A nonsignificant association with self-reported exposure to asbestos was observed for a small number of never smokers (eight of 83 nonsmoking cases, OR = 2.0, 95% CI 0.9 to 4.6). When examining these results and their causal implications, possible misclassification and reporting biases need to be considered.

A precise and highly reproducible analytical method was developed for the assessment of organochlorinated pesticide and polychlorinated biphenyl residues in adipose tissue (> or = 50 mg). The method can be utilized for epidemiological studies on the significance of these environmental pollutants in the etiology of breast cancer. Supercritical fluid extraction (SFE) with CO2 and modified CO2 (addition of 5% dichloromethane) is employed to remove incurred pesticide residues from adipose tissues that have been surgically removed from breast cancer patients and controls. An alumina sorbent, placed in the extracting vessel together with a specimen, removes the bulk of co-extracted lipids; a subsequent purification of the SFE extracts by column chromatography on alumina removes the remaining traces of lipids that would interfere with the gas chromatographic analysis with electron capture detection. The method was tested by analyzing a Certified Reference Material 430 pork fat with known amounts of pesticide residues that are commonly found in fat or in foods with a high fat content. The recoveries of analytes ranged from 73.4% for endrin to 115% for alpha-, beta- and gamma-hexachlorocyclohexane, hexachlorobenzene and dieldrin, with standard deviations of 4-12% for individual analytes. The analysis of adipose tissue for organochlorinated compounds on the basis of this new method suggested that the pesticide levels were higher in breast cancer patients than in controls. However, the small number of samples analyzed in this study (n = 5, both groups) precludes definitive conclusions. The most abundant compounds in both cases and controls were p, p-DDE (379 +/- 286 and 160 +/- 149 p.p.b.) and PCB (223 +/- 145 and 124 +/- 65.7 p.p.b.), followed by the termiticide chlordane residues oxychlordane and transnonachlor.