Polychlorinated biphenyl serum concentrations, lifestyle and time-to-pregnancy.

BACKGROUND: Consumption of fish contaminated with polychlorinated biphenyls (PCBs) and prenatal PCB serum concentrations have been associated with a longer time-to-pregnancy (TTP). However, the relationship between preconception serum PCBs concentrations and TTP has not been previously studied. METHODS: Eighty-three women (contributing 442 menstrual cycles) planning pregnancies completed daily diaries regarding menstruation, intercourse, home pregnancy test results, and reported use of alcohol and cigarettes. TTP denoted the number of observed menstrual cycles required for pregnancy. Preconception blood specimens underwent toxicologic analysis for 76 PCB congeners via gas chromatography with electron capture; serum lipids were quantified with enzymatic methods. A priori, PCB congeners were summed into a total and three groupings-estrogenic, anti-estrogenic and other-and entered into discrete analogs of Cox models with time-varying covariates to estimate fecundability odds ratios (FOR) and corresponding 95% confidence intervals (CIs). RESULTS: Estrogenic and anti-estrogenic PCB concentrations (ng/g serum) conferred reduced FORs in fully adjusted models (0.32; 95% CI 0.03, 3.90 and 0.01: 95% CI < 0.00, 1.99, respectively). Reduced FORs (0.96) were observed for alcohol consumption standardized to a 28-day menstrual cycle in the same adjusted model (FOR = 0.96; 95% CI 0.93, 1.00). CONCLUSIONS: These data suggest that environmental exposures including those amenable to change, such as alcohol consumption, may impact female fecundity. The findings are sensitive to model specification and PCB groupings, underscoring the need to further assess the impact of chemical mixtures on sensitive reproductive outcomes, such as TTP, especially in the context of lifestyle factors which are amenable to change, thereby improving reproductive health.

Longitudinal study of babies born to mothers enrolled in a preconception prospective pregnancy study: study design and methodology, New York State Angler cohort study.

Persistent environmental chemicals such as organochlorine pesticides and polychlorinated biphenyls (PCBs) have been associated with alterations in fetal development and child health including subtle differences in developmental status. Previous prospective studies have ascertained prenatal or postnatal exposures but none have been designed to assess exposures at critical windows including preconception. To address this gap, we followed infants born to mothers recruited prior to conception in the New York State Prospective Pregnancy Study to assess feasibility issues including acceptability of a relatively invasive study protocol during the child's first 2 years of life. Longitudinal measurements on health, development, and growth were obtained from 53 live-born infants; 49 families consented to standardized in-home neurodevelopmental and psychosocial evaluations at 12 and 24 months of age. Nineteen participating parents consented to the collection of blood from infants for lead thyroid and PCB levels. Despite the intensive data collection protocol over 2 years coupled with the mothers having completed an intensive prospective pregnancy protocol, we found parents readily open to continued participation in a longitudinal study involving their children. Suggestions for conducting in-home assessments include use of a consistent contact nurse, comprehensive parent-friendly developmental assessment tools with some interim assessment by parent report, and periodic team visits.

Infecundity and consumption of polychlorinated biphenyl-contaminated fish.

Biologic capacity for reproduction, or fecundity, may be threatened by environmental contaminants, especially compounds capable of disrupting endocrine pathways. Telephone interviews that focused on reproductive events were conducted with female members of the New York State Angler Cohort Study who became pregnant between 1991 and 1993 and who reported known time to pregnancy (N = 895; 73%). Consumption of polychlorinated biphenyl-contaminated Lake Ontario sportfish and other factors were ascertained in 1991. The authors classified the women as follows: (a) fecund (time to pregnancy < or =12 cycles; n = 723); (b) having resolved infecundity (time to pregnancy > 12 cycles; n = 81); or (c) having unresolved infecundity (time to pregnancy > 12 cycles without pregnancy; n = 94). Adjusted odds ratios for duration of fish consumption for both resolved and unresolved infecundity were elevated (1.46 and 1.19, respectively), although confidence intervals included unity. Frequency of recent fish consumption was associated with an increased risk for select categories, although confidence intervals included one.

Alcohol consumption and lung cancer: a review of the epidemiologic evidence.

A role for alcohol consumption in lung cancer etiology has been suggested in some studies, but this possible relationship has been often regarded with skepticism, with any indication of an association being attributed to confounding by cigarette smoking. The purpose of this work was to review the epidemiological evidence for an association of alcohol and lung cancer and to identify gaps in that research. The studies reviewed here provide some indication that alcohol and particularly beer intake may increase lung cancer risk after controlling for cigarette smoking. Although the evidence is not conclusive, it warrants additional consideration of alcohol as a risk factor in lung cancer etiology, independent of cigarette smoking. Recommendations for future studies are provided.

Parental consumption of contaminated sport fish from Lake Ontario and predicted fecundability.

Wildlife studies suggest that consumption of contaminated fish from the Great Lakes may expose humans to polychlorinated biphenyls and persistent chlorinated pesticides. To assess whether time to pregnancy or fecundability is affected, we conducted a telephone survey in 1993 with female members of the New York State Angler Cohort Study who were considering pregnancy between 1991 and 1994 (N = 2,445). Among the 1,234 (50%) women who became pregnant, 895 (73%) had a known time to pregnancy. Upon enrollment into the cohort in 1991, both partners reported duration and frequency of Lake Ontario sport fish consumption. We estimated lifetime exposure to polychlorinated biphenyls from recent consumption and used a discrete-time analog of Cox proportional hazards analysis to estimate conditional fecundability ratios and 95% confidence intervals (CIs) for fish consumption among couples with complete exposure data who discontinued birth control to become pregnant (N = 575). Maternal consumption of fish for 3-6 years was associated with reduced fecundability (fecundability ratio = 0.75; 95% CI = 0.59-0.91), as was more than a monthly fish meal in 1991 (fecundability ratio = 0.73; 95% CI = 0.54-0.98). Our findings suggest that maternal but not paternal consumption of contaminated fish may reduce fecundability among couples attempting pregnancy.

Apolipoprotein E genetic polymorphism, serum lipoproteins, and breast cancer risk.

Apolipoprotein E (apoE) is a polymorphic gene involved in lipid metabolism with three common variant alleles (epsilon2, epsilon3, and epsilon4). The epsilon4 allele has been associated with elevated levels of cholesterol as well as greater risk of coronary heart disease and Alzheimer's disease. In this case-control study we examined whether apoE genotype affected the association between serum lipids and breast cancer risk. In a subset of a study in western New York, 260 women with incident, primary breast cancer and 332 community controls were interviewed and provided blood samples. Polymerase chain reaction-restriction fragment length polymorphism analyses of the apoE polymorphism were performed. Participants were classified as apoE2 (epsilon2, epsilon2 or epsilon2, epsilon3), apoE3 (epsilon3, epsilon3), or apoE4 (epsilon4, epsilon4 or epsilon4, epsilon3). No unconditional logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with the apoE3 genotype, there were no associations with risk for women with the apoE2 (OR=1.0; 95% CI=0. 91-1.64) or apoE4 genotype (OR=0.97; 95% CI=0.63-1.54). Higher serum levels of total cholesterol, HDL cholesterol, and LDL cholesterol were not associated with risk, either in the total sample or among subgroups of women defined by apoE genotype. Women with the highest serum triglyceride levels had an increase in risk (OR=1.63; 95% CI=1. 03-2.59) compared to women with the lowest levels. This effect was not apparent among women with the apoE2 or apoE3 genotype, but much stronger among women with the apoE4 genotype (OR=4.69; 95% CI=1. 49-14.7). These data suggest that the apoE4 genotype may modify the association between serum triglycerides and breast cancer risk.

Alcohol dehydrogenase 3 genotype modification of the association of alcohol consumption with breast cancer risk.

OBJECTIVES: Because alcohol dehydrogenase 3 (ADH3) is rate-limiting in alcohol oxidation and is polymorphic, we examined ADH3 genotype in relation to alcohol intake and breast cancer risk. METHODS: We conducted a case-control study among Caucasian women aged 40-85 with incident, pathologically confirmed breast cancer and controls, frequency-matched on age and county. Queries included alcohol intake in the past 20 years. Genomic DNA was genotyped for the exon VIII ADH polymorphism by PCR followed by restriction enzyme digestion. Computation of odds ratios (OR) and 95% confidence intervals (CI) was by unconditional logistic regression. RESULTS: We found increased risk among pre- (OR 2.3, 95%, CI 1.2-4.3) but not postmenopausal women (OR 1.1, 95% CI 0.7-1.7) associated with ADH3(1-1) compared to ADH3(1-2) and ADH3(2-2) genotypes. Risk was increased for premenopausal women with the ADH3(1-1) genotype and alcohol intake above the median (OR 3.6, 95% CI 1.5-8.8) compared to lighter drinkers with the ADH3(2-2) or ADH3(1-2) genotypes. ORs were close to null for premenopausal women in other drinking and genotype groups and for postmenopausal women categorized by genotype and alcohol consumption. CONCLUSION: Among premenopausal women there may be a group more genetically susceptible to an alcohol consumption effect on breast cancer risk.

Work and leisure time physical activity and mortality in men and women from a general population sample.

PURPOSE: The purpose of this study was to examine the long-term relationships between total physical activity and mortality from all causes and coronary heart disease (CHD) in the general population. METHODS: A prospective design was used, following participants for 29 years, beginning in 1960. The study population consisted of a randomly selected sample of white male (n = 698) and female (n = 763) residents of Buffalo, New York with a 79.0% participation rate and follow-up rates of 96.0% and 90.2% in males and females, respectively. At baseline, comprehensive information was obtained regarding participants' usual physical activity at work and during leisure time. RESULTS: As of December 31, 1989, three hundred and two (43.3%) men and 276 (41.0%) women died, 109 (15.6%) and 81 (10.6%) from CHD, respectively. In men, a significant interaction was found between activity and body mass index (BMI) for both outcomes. In women, a significant activity by age interaction was observed. In non-obese men (BMI<27.02), activity was inversely associated with all-cause [relative risk (RR) = 0.59; 95% confidence interval (CI), 0.39-0.89] and CHD mortality (RR = 0.39; 95% CI, 0.18-0.83), independent from the effects of age and education. No such associations were found in obese men and increased risks could not be ruled out. Among women, younger participants (age <60 years) had a significantly reduced risk of CHD death with increased activity (RR = 0.26; 95% CI, 0.07-0.99). No other significant associations were observed. CONCLUSIONS: Physical activity favorably influences mortality risks in non-obese men and younger women. Gender-specific factors should be considered for potential effect modification.

Risk of premenopausal breast cancer in association with occupational exposure to polycyclic aromatic hydrocarbons and benzene.

OBJECTIVES: This study examined the relationship between risk of premenopausal breast cancer and occupational exposure to benzene and polycyclic aromatic hydrocarbons (PAH) and whether the proposed relationship between PAH and breast cancer differed by tumor estrogen receptor (ER) status. METHODS: In a case-referent study of premenopausal breast cancer, occupational histories and other information were obtained through interviews, and job-exposure matrices were used to assess exposure to PAH and benzene. RESULTS: A dose-response relationship for the probability of exposure to benzene [low: odds ratio (OR) 1.64, 95% confidence interval (95% CI) 0.64-4.21; high: OR 1.95, 95% CI 1.14-3.33) and to PAH (low: OR 1.56, 95% CI 0.78-3.12; high: OR 2.40, 95% CI 0.96-6.01). Risk increased with duration of exposure to benzene, but not to PAH. A dose-response relationship was not evident for the intensity of exposure to benzene or to PAH. When analyses were stratified by tumor ER status, PAH exposure was related to a greater increase in the risk of ER-positive (OR 2.27, 95% CI 1.14-4.54) than ER-negative (OR 1.12, 95% CI 0.47-2.64) breast cancer. Risk of ER-positive, but not ER-negative, tumors increased with the probability of exposure to PAH. CONCLUSIONS: The findings suggest an association between risk and occupational exposure to benzene. Although it was difficult to study PAH independently of benzene, there was some suggestion of an association between PAH exposure and ER-positive tumors. These data should be interpreted with caution because of the limitations of this study, including low-response rates and small numbers of exposed persons.

Paternal Lake Ontario fish consumption and risk of conception delay, New York State Angler Cohort.

The aquatic ecosystems of the Great Lakes are contaminated with a variety of compounds, some of which are considered reproductive toxicants. Few studies of paternal fish consumption and reproductive endpoints have been undertaken and serve as the impetus for study. Standardized telephone interviews were conducted with 2445 female members of the New York State Angler Cohort (82% response) to update reproductive profiles and to ascertain specific information on time-to-pregnancy (TTP). The study sample includes women with a known TTP and paternal fish consumption data (n=785). Conception delay was defined as more than 12 cycles of unprotected intercourse to achieve pregnancy. Paternal fish consumption was assessed by three measures: frequency of Lake Ontario sport fish meals in 1991, numbers of years eating fish, and estimated PCB exposure from fish consumption. Adjusted ORs for number of fish meals, based on logistic regression, ranged from 0.69 to 0.80; from 0.61 to 0.82 for number of years eating fish; and from 0.44 to 1.14 for quartiles of estimated PCB exposure from fish consumption. All confidence intervals included one. These findings suggest that, based on paternal self-reports, Lake Ontario fish consumption does not increase the risk of conception delay.

Comparison of PCB congeners and pesticide levels between serum and milk from lactating women.

Samples of blood and milk were obtained from lactating women participating in the New York State Angler study. A total of seven women gave one blood and one milk sample at time intervals between blood and milk collection different for each woman. The time between samples varied from 3 to 318 days. One subject provided a second milk sample 219 days after the first milk sample. The samples were analyzed for 69 PCB congeners, DDE (a metabolite of DDT), Mirex, and hexachlorobenzene (HCB). Lipid content was determined by gravimetric analysis. The congener profiles in serum and milk were similar for each individual but different among all subjects. The sum of the concentrations of the congeners present above the limit of detection was used to estimate the total PCB concentration that was in the range of 2.6 to 5.8 ng/g of serum and 3.5 to 14.1 ng/g of milk. The ratio of serum to milk concentrations varied from 0.18 to 1.66 with a mean of 0.65+/-0.49 showing no consistency among individuals prior to adjusting the data for lipid content. The total PCB levels normalized for lipid content were 320-728 ng/g of serum lipid and 239-428 ng/g of milk lipid. The range of the lipid adjusted serum/milk ratio was 1.1 to 2.8 and the mean+/-SD serum/milk ratio was 1.9+/-0.5. The ranges of lipid adjusted serum concentration of DDE, HCB, and Mirex were 95 to 591, 8 to 48, and 3 to 29 ng/g lipid, respectively. The ranges of lipid adjusted milk concentration of DDE, HCB, and Mirex were 90 to 577, 11 to 22, and 1 to 10 ng/g lipid, respectively. For DDE, HCB, and Mirex, the means of the individual lipid adjusted serum to milk ratios were 1.5+/-0.7, 2.5+/-1.5, and 5. 3+/-4.6, respectively. Considerable differences were found among lipid adjusted concentrations of these environmental pollutants in serum and milk samples from the same individual. This suggests that body burden estimates in lactating women using different matrices may not be equivalent even when lipid adjusted values are used.

An evaluation of proposed frameworks for grouping polychlorinated biphenyl (PCB) congener data into meaningful analytic units.

BACKGROUND: Polychlorinated biphenyls (PCBs) have been associated with a variety of health outcomes. Enhanced laboratory techniques can provide a relatively large number of individual PCB congeners for investigation. However, to date there are no established frameworks for grouping a large number of PCB congeners into meaningful analytic units. METHODS: In a case-control study of serum PCB levels on breast cancer risk, measured levels of 56 PCB congener peaks were available for analysis. We considered several approaches for grouping these compounds based on 1) chlorination, 2) factor analysis, 3) enzyme induction, 4) enzyme induction and occurrence, and 5) enzyme induction, occurrence, and other toxicological aspects. The utility of a framework was based on the mechanism of biologic actions within each framework, lack of collinearity among congener groups, and frequency of detection of PCB congener groups in measured serum levels of 192 healthy postmenopausal women. RESULTS: Most participants had detectable levels for the proposed PCB congeners groups, using degree of chlorination as a grouping framework. In addition, the previously proposed grouping approach based on enzyme induction, occurrence, and other toxicological aspects was an applicable alternative to the crude approach of grouping by degree of chlorination. Grouping these congeners with respect to P450 enzyme induction activity, and the previously proposed framework based on enzyme induction and occurrence, did not fit these data as well, because only a small proportion of participants had detectable levels for the congener groups with the greatest toxicological potential. Statistical grouping did not result in an interpretable and meaningful clustering of these exposures. CONCLUSIONS: In these data, grouping with respect to degree of chlorination and the previously proposed framework based on enzyme induction, occurrence, and other toxicological aspects were the most useful approaches to reducing a large number of PCB congeners into meaningful analytic units. Factors affecting the utility of the proposed grouping frameworks are discussed.

Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer.

Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in human breast carcinogenesis. Dietary sources of antioxidants (chemical) and endogenous antioxidants (enzymatic), including the polymorphic manganese superoxide dismutase (MnSOD), can act to reduce the load of oxidative stress. We hypothesized that the valine-to-alanine substitution that seems to alter transport of the enzyme into the mitochondrion, changing its efficacy in fighting oxidative stress, was associated with breast cancer risk and that a diet rich in sources of antioxidants could ameliorate the effects on risk. Data were collected in a case-control study of diet and breast cancer in western New York from 1986 to 1991. Caucasian women with incident, primary, histologically confirmed breast cancer were frequency-matched on age and county of residence to community controls. Blood specimens were collected and processed from a subset of participants in the study (266 cases and 295 controls). Using a RFLP that distinguishes a valine (V) to alanine (A) change in the -9 position in the signal sequence of the protein for MnSOD, we characterized MnSOD genotypes in relation to breast cancer risk. We also evaluated the effect of the polymorphism on risk among low and high consumers of fruits and vegetables. Premenopausal women who were homozygous for the A allele had a 4-fold increase in breast cancer risk in comparison to those with 1 or 2 V alleles (odds ratio, 4.3; 95% confidence interval, 1.7-10.8). Risk was most pronounced among women below the median consumption of fruits and vegetables and of dietary ascorbic acid and alpha-tocopherol, with little increased risk for those with diets rich in these foods. Relationships were weaker among postmenopausal women, although the MnSOD AA genotype was associated with an almost 2-fold increase in risk (odds ratio, 1.8; confidence interval, 0.9-3.6). No appreciable modification of risk by diet was detected for these older women. These data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk, particularly in premenopausal women. The finding that risk was greatest among women who consumed lower amounts of dietary antioxidants and was minimal among high consumers indicates that a diet rich in sources of antioxidants may minimize the deleterious effects of the MnSOD polymorphism, thereby supporting public health recommendations for the consumption of diets rich in fruits and vegetables as a preventive measure against cancer.

Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer risk.

In experimental systems, polychlorinated biphenyls (PCBs) induce cytochrome P4501A1 (CYP1A1), which is involved in metabolism of steroid hormones and polycyclic aromatic hydrocarbons in humans. A genetic polymorphism coding for a valine to isoleucine substitution in exon 7 has been associated with lung cancer risk in Japanese populations. In a previous study, we found no association between CYP1A1 genotype and breast cancer risk. However, we were interested in determining whether genotype would relate to risk when PCB body burden was taken into account. In a subset of a case-control study in western New York, 154 postmenopausal women with incident, primary, histologically confirmed postmenopausal breast cancer and 192 community controls were interviewed and underwent phlebotomy. Serum levels of 56 PCB peaks were determined by high resolution gas chromatography with electron capture. PCR-RFLP analyses of the CYP1A1 polymorphism were performed. Unconditional logistic regression was used to compute adjusted odds ratios and 95% confidence intervals. Among women with serum PCB levels above the median of the distribution in the control group, there was increased risk of breast cancer associated with the presence of at least one valine allele, compared with women who were homozygous for the isoleucine alleles (odds ratio, 2.93; 95% confidence interval, 1.17-7.36). Among women with low PCB body burden, no association between CYP1A1 genotype and breast cancer risk was observed. Adjustment for serum lipids and body mass index did not affect the magnitude of the observed associations. PCB body burden may modify the effect of the polymorphism on postmenopausal breast cancer risk through increased CYP1A1 enzyme induction or by activation by specific PCB congeners. These results should be considered preliminary, pending replication by other studies.

Risk of premenopausal breast cancer and patterns of established breast cancer risk factors among teachers and nurses.

BACKGROUND: Contrasting results have been published regarding the risk of breast cancer among teachers and nurses. Confounding by reproductive factors may explain the increased risk observed among women in these occupations as information on those factors were not available in most studies. METHODS: We examined the risk of premenopausal breast cancer among teachers and nurses using occupational histories in a case-control study where information on established risk factors was available. RESULTS: Having ever held a teaching job was not related to breast cancer (OR = 0.74, 95% CI = 0.44-1.28) and women who worked for 10 years or less in this occupation had a non-significant deficit of risk (OR = 0.52, 95% CI = 0.27-1.02). No elevation in risk was found in association with having ever been a nurse (OR = 0.85, 95% CI = 0.45-1.61) or with duration of nursing. Although direct comparison of established risk factors among teachers and nurses and other women in the study showed some evidence of differential distribution, especially when comparing teachers to other women, adjustment for reproductive variables and other breast cancer risk factors did not change the results of this study. CONCLUSION: These findings suggest that teachers and nurses are not at an increased risk of breast cancer. This study also suggests that established risk factors for premenopausal breast cancer may not explain the elevation of risk found in other studies of teachers and nurses. However, this conclusion is limited by the fact that in the present study teachers and nurses had lower than expected breast cancer risk with or without adjustment for established risk factors. Limitations of this study such as low response rates and limited statistical power should be considered in the interpretation of these findings.

Innovative multidisciplinary research in environmental epidemiology: the challenges and needs.

The ability of epidemiology to determine the relationships between health and environmental insults has become exceedingly difficult. The multifactorial nature of disease and the diversity of the insults, which include biologic, physical, social and cultural factors, combined with genetic susceptibility, suggest the need to develop better models of multidisciplinary epidemiologic investigation. This paper highlights the needs of an environmental epidemiologic team, discusses ways to incorporate new ideas across disciplines and to integrate constructs and paradigms of social, ecological, cultural and population determinants with individual-based exposure assessments. Innovation will be the key to the survival and increasing importance of epidemiology in addressing the public health needs of the future, but what are the ways to enhance and encourage creativity in environmental epidemiology? The process of self-renewal and continuing education will be highlighted. Additionally, the complexity of the problems and the need for clear supervision and control of multidisciplinary research efforts require a forum of communication and an 'information-processing approach' beyond those in traditional epidemiologic studies. New approaches in data management and medical informatics must be incorporated into the epidemiologic investigative framework. Methods to be included should focus on opportunities for computer-supported sharing of ideas. Such capabilities minimise the geographic distances and the disparate knowledge and training of the investigators and bring the team closer to the objectives and functions inherent in multidisciplinary investigation.

Risk of recurrent spontaneous abortion, cigarette smoking, and genetic polymorphisms in NAT2 and GSTM1.

Maternal smoking increases the risk of spontaneous abortion. Polymorphic N-acetyltransferase (NAT2) and glutathione S-transferase (GSTM1) affect metabolism of some mutagens found in tobacco smoke. Genotypes and smoking were studied in women with at least two spontaneous abortions (N = 32) and those with at least two livebirths (N = 179). Smoking slightly increased risk (odds ratio = 1.3; 95% confidence interval = 0.6-2.9), but NAT2 and GSTM1 did not. NAT2 or GSTM1 polymorphisms did not appreciably modify smoking-related risk.

Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk.

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols. In a case-control study, we evaluated the association of the low-activity allele (COMT(Met)) with breast cancer risk. Compared to women with COMT(Val/Val), COMT(Met/Met) was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The association of risk with at least one low-activity COMT(Met) allele was strongest among the heaviest premenopausal women (OR, 5.7; CI, 1.1-30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.

Breast cancer risk and lifetime occupational history: employment in professional and managerial occupations.

OBJECTIVE: In this case-control study, occupational histories were used to assess the relation between risk of breast cancer and employment in professional and managerial occupations while adjusting for reproductive and other risk factors. METHODS: Incident, primary, female cases of breast cancer diagnosed between 1986 and 1991, and randomly selected controls were interviewed to obtain detailed medical, reproductive, and occupational histories. Mantel-Haenszel crude odds ratios (OR) and 95% confidence intervals (95% CIs) were used to estimate risk of breast cancer related to the job of longest duration. Unconditional logistic regression was used to estimate crude and adjusted ORs and 95% CIs associated with having ever been employed and duration of employment in a professional or managerial occupation. RESULTS: A non-significant threefold increase in risk was found among premenopausal women whose major job was in the occupational category of precision production, craft, and repair (95% CI 0.90 to 20.35). No increase in risk was found for premenopausal women whose major job was a managerial or professional occupation. However, an inverse relation between risk of premenopausal breast cancer and having ever held a professional or managerial job was observed (OR 0.53, 95% CI 0.34 to 0.82). This relation was strongest for women who worked one to 10 years (OR 0.47, 95% CI 0.29 to 0.77). Postmenopausal breast cancer was not related to professional and managerial employment. CONCLUSIONS: In this population, employment in professional and managerial occupations is not associated with postmenopausal risk of breast cancer, but seems to be related to a reduction in risk of premenopausal breast cancer. Methodological limitations of this study including response rates are discussed.

Environmental organochlorine exposure and postmenopausal breast cancer risk.

Environmental exposure to organochlorine compounds has been associated with a potential role in breast cancer etiology, but results from previous investigations yielded inconsistent results. In this case-control study, we examined the effect of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), hexachlorobenzene (HCB), mirex, and several measures of polychlorinated biphenyls (PCBs) on postmenopausal breast cancer risk. The study sample included 154 primary, incident, histologically confirmed, postmenopausal breast cancer cases and 192 postmenopausal community controls. Usual diet, reproductive and medical histories, and other lifestyle information was obtained by an extensive in person interview. Serum levels (ng/g) of DDE, HCB, mirex, and 73 PCB congeners were determined by gas chromatography with electron capture. PCB exposure was examined as total measured PCB levels, total number of detected PCB peaks, and three PCB congener groups. In the total sample, there was no evidence of an adverse effect of serum levels of DDE [odds ratio (OR), 1.34; 95% confidence interval (CI) 0.71-2.55], HCB (OR, 0.81; 95% CI, 0.43-1.53), or mirex (OR, 1.37; 95% CI, 0.78-2.39). Further, higher serum levels of total PCBs (OR, 1.14; 95% CI, 0.61-2.15), moderately chlorinated PCBs (OR, 1.37; 95% CI, 0.73-2.59), more highly chlorinated PCBs (OR, 1.19; 95% CI, 0.60-2.36), or greater number of detected peaks (OR, 1.34; 95% CI, 0.72-2.47) were not associated with increased risk. There was some indication of a modest increase in risk for women with detectable levels of less chlorinated PCBs (OR, 1.66; 95% CI, 1.07-2.88). Among parous women who had never lactated, there was some evidence for increased risk, associated with having detectable levels of mirex (OR, 2.42; 95% CI, 0.98-4.32), higher serum concentrations of total PCBs (OR, 2.87; 95% CI, 1.01-7.29), moderately chlorinated PCBs (OR, 3.57; 95% CI, 1.10-8.60), and greater numbers of detected PCB congeners (OR, 3.31; 95% CI, 1.04-11.3). These results suggest that an increase in risk of postmenopausal breast cancer associated with environmental exposure to PCBs and mirex, if at all present, is restricted to parous women who had never breast-fed an infant. Future studies should consider lactation history of participants, as well as use similar epidemiological and laboratory methodologies, to ensure comparability of results across studies.