Self-Reported Chemicals Exposure, Beliefs About Disease Causation, and Risk of Breast Cancer in the Cape Cod Breast Cancer and Environment Study: A Case-Control Study

BACKGROUND: Household cleaning and pesticide products may contribute to breast cancer because many contain endocrine disrupting chemicals or mammary gland carcinogens. This population-based case-control study investigated whether use of household cleaners and pesticides increases breast cancer risk. METHODS: Participants were 787 Cape Cod, Massachusetts, women diagnosed with breast cancer between 1988 and 1995 and 721 controls. Telephone interviews asked about product use, beliefs about breast cancer etiology, and established and suspected breast cancer risk factors. To evaluate potential recall bias, we stratified product-use odds ratios by beliefs about whether chemicals and pollutants contribute to breast cancer; we compared these results with odds ratios for family history (which are less subject to recall bias) stratified by beliefs about heredity. RESULTS: Breast cancer risk increased two-fold in the highest compared with lowest quartile of self-reported combined cleaning product use (Adjusted OR = 2.1, 95% CI: 1.4, 3.3) and combined air freshener use (Adjusted OR = 1.9, 95% CI: 1.2, 3.0). Little association was observed with pesticide use. In stratified analyses, cleaning products odds ratios were more elevated among participants who believed pollutants contribute "a lot" to breast cancer and moved towards the null among the other participants. In comparison, the odds ratio for breast cancer and family history was markedly higher among women who believed that heredity contributes "a lot" (OR = 2.6, 95% CI: 1.9, 3.6) and not elevated among others (OR = 0.7, 95% CI: 0.5, 1.1). CONCLUSIONS: Results of this study suggest that cleaning product use contributes to increased breast cancer risk. However, results also highlight the difficulty of distinguishing in retrospective self-report studies between valid associations and the influence of recall bias. Recall bias may influence higher odds ratios for product use among participants who believed that chemicals and pollutants contribute to breast cancer. Alternatively, the influence of experience on beliefs is another explanation, illustrated by the protective odds ratio for family history among women who do not believe heredity contributes "a lot." Because exposure to chemicals from household cleaning products is a biologically plausible cause of breast cancer and avoidable, associations reported here should be further examined prospectively.Massachusetts Legislature; Massachusetts Department of Public Health; Susan S. Bailis Breast Cancer Research Fund at Silent Spring Institute; United States Centers for Disease Control and Prevention (R01 DP000218-01, 1H75EH000377-01

Impact of tetrachloroethylene-contaminated drinking water on the risk of breast cancer: Using a dose model to assess exposure in a case-control study

BACKGROUND: A population-based case-control study was undertaken in 1997 to investigate the association between tetrachloroethylene (PCE) exposure from public drinking water and breast cancer among permanent residents of the Cape Cod region of Massachusetts. PCE, a volatile organic chemical, leached from the vinyl lining of certain water distribution pipes into drinking water from the late 1960s through the early 1980s. The measure of exposure in the original study, referred to as the relative delivered dose (RDD), was based on an amount of PCE in the tap water entering the home and estimated with a mathematical model that involved only characteristics of the distribution system. METHODS: In the current analysis, we constructed a personal delivered dose (PDD) model that included personal information on tap water consumption and bathing habits so that inhalation, ingestion, and dermal absorption were also considered. We reanalyzed the association between PCE and breast cancer and compared the results to the original RDD analysis of subjects with complete data. RESULTS: The PDD model produced higher adjusted odds ratios than the RDD model for exposures > 50(th )and >75(th )percentile when shorter latency periods were considered, and for exposures < 50(th )and >90(th )percentile when longer latency periods were considered. Overall, however, the results from the PDD analysis did not differ greatly from the RDD analysis. CONCLUSION: The inputs that most heavily influenced the PDD model were initial water concentration and duration of exposure. These variables were also included in the RDD model. In this study population, personal factors like bath and shower temperature, bathing frequencies and durations, and water consumption did not differ greatly among subjects, so including this information in the model did not significantly change subjects' exposure classification

Spatial analysis of bladder, kidney, and pancreatic cancer on upper Cape Cod: an application of generalized additive models to case-control data

<p>Abstract</p> <p>Background</p> <p>In 1988, elevated cancer incidence in upper Cape Cod, Massachusetts prompted a large epidemiological study of nine cancers to investigate possible environmental risk factors. Positive associations were observed, but explained only a portion of the excess cancer incidence. This case-control study provided detailed information on individual-level covariates and residential history that can be spatially analyzed using generalized additive models (GAMs) and geographical information systems (GIS).</p> <p>Methods</p> <p>We investigated the association between residence and bladder, kidney, and pancreatic cancer on upper Cape Cod. We estimated adjusted odds ratios using GAMs, smoothing on location. A 40-year residential history allowed for latency restrictions. We mapped spatially continuous odds ratios using GIS and identified statistically significant clusters using permutation tests.</p> <p>Results</p> <p>Maps of bladder cancer are essentially flat ignoring latency, but show a statistically significant hot spot near known Massachusetts Military Reservation (MMR) groundwater plumes when 15 years latency is assumed. The kidney cancer map shows significantly increased ORs in the south of the study area and decreased ORs in the north.</p> <p>Conclusion</p> <p>Spatial epidemiology using individual level data from population-based studies addresses many methodological criticisms of cluster studies and generates new exposure hypotheses. Our results provide evidence for spatial clustering of bladder cancer near MMR plumes that suggest further investigation using detailed exposure modeling.</p

Tetrachloroethylene-contaminated drinking water in Massachusetts and the risk of colon-rectum, lung, and other cancers.

We conducted a population-based case-control study to evaluate the relationship between cancer of the colon-rectum (n = 326), lung (n = 252), brain (n = 37), and pancreas (n = 37), and exposure to tetrachloroethylene (PCE) from public drinking water. Subjects were exposed to PCE when it leached from the vinyl lining of drinking-water distribution pipes. Relative delivered dose of PCE was estimated using a model that took into account residential location, years of residence, water flow, and pipe characteristics. Adjusted odds ratios (ORs) for lung cancer were moderately elevated among subjects whose exposure level was above the 90th percentile whether or not a latent period was assumed [ORs and 95% confidence intervals (CIs), 3.7 (1.0-11.7), 3.3 (0.6-13.4), 6.2 (1.1-31.6), and 19.3 (2.5-141.7) for 0, 5, 7, and 9 years of latency, respectively]. The adjusted ORs for colon-rectum cancer were modestly elevated among ever-exposed subjects as more years of latency were assumed [OR and CI, 1.7 (0.8-3.8) and 2.0 (0.6-5.8) for 11 and 13 years of latency, respectively]. These elevated ORs stemmed mainly from associations with rectal cancer. Adjusted ORs for rectal cancer among ever-exposed subjects were more elevated [OR and CI, 2.6 (0. 8-6.7) and 3.1 (0.7-10.9) for 11 and 13 years of latency, respectively] than were corresponding estimates for colon cancer [OR and CI, 1.3 (0.5-3.5) and 1.5 (0.3-5.8) for 11 and 13 years of latency, respectively]. These results provide evidence for an association between PCE-contaminated public drinking water and cancer of the lung and, possibly, cancer of the colon-rectum

Using Residential History and Groundwater Modeling to Examine Drinking Water Exposure and Breast Cancer

BACKGROUND. Spatial analyses of case-control data have suggested a possible link between breast cancer and groundwater plumes in upper Cape Cod, Massachusetts. OBJECTIVE. We integrated residential histories, public water distribution systems, and groundwater modeling within geographic information systems (GIS) to examine the association between exposure to drinking water that has been contaminated by wastewater effluent and breast cancer. METHODS. Exposure was assessed from 1947 to 1993 for 638 breast cancer cases who were diagnosed from 1983 to 1993 and 842 controls; we took into account residential mobility and drinking water source. To estimate the historical impact of effluent on drinking water wells, we modified a modular three-dimensional finite-difference groundwater model (MODFLOW) from the U.S. Geological Survey. The analyses included latency and exposure duration. RESULTS. Wastewater effluent impacted the drinking water wells of study participants as early as 1966. For > 0-5 years of exposure (versus no exposure), associations were generally null. Adjusted odds ratios (AORs) for > 10 years of exposure were slightly increased, assuming latency periods of 0 or 10 years [AOR = 1.3; 95% confidence interval (CI), 0.9-1.9 and AOR = 1.6; 95% CI, 0.8-3.2, respectively]. Statistically significant associations were estimated for ever-exposed versus never-exposed women when a 20-year latency period was assumed (AOR = 1.9; 95% CI, 1.0-3.4). A sensitivity analysis that classified exposures assuming lower well-pumping rates showed similar results. CONCLUSION. We investigated the hypothesis generated by earlier spatial analyses that exposure to drinking water contaminated by wastewater effluent may be associated with breast cancer. Using a detailed exposure assessment, we found an association with breast cancer that increased with longer latency and greater exposure duration.National Cancer Institute (5R03CA119703-02); National Institute of Environmental Health Sciences (5P42 ES007381

Renal Hyperfiltration and the Development of Microalbuminuria in Type 1 Diabetes

OBJECTIVE: The purpose of this study was to examine prospectively whether renal hyperfiltration is associated with the development of microalbuminuria in patients with type 1 diabetes, after taking into account known risk factors. RESEARCH DESIGN AND METHODS: The study group comprised 426 participants with normoalbuminuria from the First Joslin Kidney Study, followed for 15 years. Glomerular filtration rate was estimated by serum cystatin C, and hyperfiltration was defined as exceeding the 97.5th percentile of the sex-specific distribution of a similarly aged, nondiabetic population (134 and 149 ml/min per 1.73 m2 for men and women, respectively). The outcome was time to microalbuminuria development (multiple albumin excretion rate >30 μg/min). Hazard ratios (HRs) for microalbuminuria were calculated at 5, 10, and 15 years. RESULTS: Renal hyperfiltration was present in 24% of the study group and did not increase the risk of developing microalbuminuria. The unadjusted HR for microalbuminuria comparing those with and without hyperfiltration at baseline was 0.8 (95% CI 0.4–1.7) during the first 5 years, 1.0 (0.6–1.7) during the first 10 years, and 0.8 (0.5–1.4) during 15 years of follow-up. The model adjusted for baseline known risk factors including A1C, age at diagnosis of diabetes, diabetes duration, and cigarette smoking resulted in similar HRs. In addition, incorporating changes in hyperfiltration status during follow-up had minimal impact on the HRs for microalbuminuria. CONCLUSION;S Renal hyperfiltration does not have an impact on the development of microalbuminuria in type 1 diabetes during 5, 10, or 15 years of follow-up.National Institutes of Health Grant (DK 041526

Cluster detection methods applied to the Upper Cape Cod cancer data

BACKGROUND: A variety of statistical methods have been suggested to assess the degree and/or the location of spatial clustering of disease cases. However, there is relatively little in the literature devoted to comparison and critique of different methods. Most of the available comparative studies rely on simulated data rather than real data sets. METHODS: We have chosen three methods currently used for examining spatial disease patterns: the M-statistic of Bonetti and Pagano; the Generalized Additive Model (GAM) method as applied by Webster; and Kulldorff's spatial scan statistic. We apply these statistics to analyze breast cancer data from the Upper Cape Cancer Incidence Study using three different latency assumptions. RESULTS: The three different latency assumptions produced three different spatial patterns of cases and controls. For 20 year latency, all three methods generally concur. However, for 15 year latency and no latency assumptions, the methods produce different results when testing for global clustering. CONCLUSION: The comparative analyses of real data sets by different statistical methods provides insight into directions for further research. We suggest a research program designed around examining real data sets to guide focused investigation of relevant features using simulated data, for the purpose of understanding how to interpret statistical methods applied to epidemiological data with a spatial component

Tetrachloroethylene-contaminated drinking water and the risk of breast cancer.

We conducted a population-based case-control study to evaluate the relationship between cases of breast cancer and exposure to tetrachloroethylene (PCE) from public drinking water ( n = 258 cases and 686 controls). Women were exposed to PCE when it leached from the vinyl lining of water distribution pipes. The relative delivered dose was estimated using an algorithm that accounted for residential history, water flow, and pipe characteristics. Only small increases in breast cancer risk were seen among ever-exposed women either when latency was ignored or when 5 to 15 years of latency was considered. No or small increases were seen among highly exposed women either when latency was ignored or when 5 years of latency was considered. However, the adjusted odds ratios (ORs) were more increased for highly exposed women when 7 and 9 years of latency, respectively, were considered (OR 1.5 95% CI 0.5-4.7 and OR 2.3, 95% CI 0.6-8.8 for the 75th percentile, and OR 2.7, 95% CI 0.4-15.8 and OR 7.6, 95% CI 0.9-161.3 for the 90th percentile). The number of highly exposed women was too small for meaningful analysis when more years of latency were considered. Because firm conclusions from these data are limited, we recently undertook a new study with a large number of more recently diagnosed cases

Perchloroethylene-contaminated drinking water and the risk of breast cancer: additional results from Cape Cod, Massachusetts, USA.

In 1998 we published the results of a study suggesting an association between breast cancer and perchloroethylene (PCE; also called tetrachloroethylene) exposure from public drinking water. The present case-control study was undertaken to evaluate this association further. The cases were composed of female residents of eight towns in the Cape Cod region of Massachusetts who had been diagnosed with breast cancer from 1987 through 1993 (n = 672). Controls were composed of demographically similar women from the same towns (n = 616). Women were exposed to PCE when it leached from the vinyl lining of water distribution pipes from the late 1960s through the early 1980s. A relative delivered dose of PCE that entered a home was estimated using an algorithm that took into account residential history, water flow, and pipe characteristics. Small to moderate elevations in risk were seen among women whose exposure levels were above the 75th and 90th percentiles when 0-15 years of latency were considered (adjusted odds ratios, 1.5-1.9 for > 75th percentile, 1.3-2.8 for > 90th percentile). When data from the present and prior studies were combined, small to moderate increases in risk were also seen among women whose exposure levels were above the 75th and 90th percentiles when 0-15 years of latency were considered (adjusted odds ratios, 1.6-1.9 for > 75th percentile, 1.3-1.9 for > 90th percentile). The results of the present study confirm those of the previous one and suggest that women with the highest PCE exposure levels have a small to moderate increased risk of breast cancer

Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Congenital Anomalies: A Retrospective Cohort Study

BACKGROUND: Prior animal and human studies of prenatal exposure to solvents including tetrachloroethylene (PCE) have shown increases in the risk of certain congenital anomalies among exposed offspring. OBJECTIVES: This retrospective cohort study examined whether PCE contamination of public drinking water supplies in Massachusetts influenced the occurrence of congenital anomalies among children whose mothers were exposed around the time of conception. METHODS: The study included 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. Mothers completed a self-administered questionnaire to gather information on all of their prior births, including the presence of anomalies, residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. RESULTS: Children whose mothers had high exposure levels around the time of conception had an increased risk of congenital anomalies. The adjusted odds ratio of all anomalies combined among children with prenatal exposure in the uppermost quartile was 1.5 (95% CI: 0.9, 2.5). No meaningful increases in the risk were seen for lower exposure levels. Increases were also observed in the risk of neural tube defects (OR: 3.5, 95% CI: 0.8, 14.0) and oral clefts (OR 3.2, 95% CI: 0.7, 15.0) among offspring with any prenatal exposure. CONCLUSION: The results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who are identified by independent records.National Institute of Environmental Health (5 P42 ES007381); National Institutes of Healt