Biomedical subjects

Ann Aschengrau

Publications and source records attributed to Ann Aschengrau.

15 recordsLinked to original sources

PubMed2006

Breast cancer risk and drinking water contaminated by wastewater: a case control study.

BACKGROUND: Drinking water contaminated by wastewater is a potential source of exposure to mammary carcinogens and endocrine disrupting compounds from commercial products and excreted natural and pharmaceutical hormones. These contaminants are hypothesized to increase breast cancer risk. Cape Cod, Massachusetts, has a history of wastewater contamination in many, but not all, of its public water supplies; and the region has a history of higher breast cancer incidence that is unexplained by the population's age, in-migration, mammography use, or established breast cancer risk factors. We conducted a case-control study to investigate whether exposure to drinking water contaminated by wastewater increases the risk of breast cancer. METHODS: Participants were 824 Cape Cod women diagnosed with breast cancer in 1988-1995 and 745 controls who lived in homes served by public drinking water supplies and never lived in a home served by a Cape Cod private well. We assessed each woman's exposure yearly since 1972 at each of her Cape Cod addresses, using nitrate nitrogen (nitrate-N) levels measured in public wells and pumping volumes for the wells. Nitrate-N is an established wastewater indicator in the region. As an alternative drinking water quality indicator, we calculated the fraction of recharge zones in residential, commercial, and pesticide land use areas. RESULTS: After controlling for established breast cancer risk factors, mammography, and length of residence on Cape Cod, results showed no consistent association between breast cancer and average annual nitrate-N (OR = 1.8; 95% CI 0.6-5.0 for > or = 1.2 vs. < .3 mg/L), the sum of annual nitrate-N concentrations (OR = 0.9; 95% CI 0.6-1.5 for > or = 10 vs. 1 to < 10 mg/L), or the number of years exposed to nitrate-N over 1 mg/L (OR = 0.9; 95% CI 0.5-1.5 for > or = 8 vs. 0 years). Variation in exposure levels was limited, with 99% of women receiving some of their water from supplies with nitrate-N levels in excess of background. The total fraction of residential, commercial, and pesticide use land in recharge zones of public supply wells was associated with a small statistically unstable higher breast cancer incidence (OR = 1.4; 95% CI 0.8-2.4 for highest compared with lowest land use), but risk did not increase for increasing land use fractions. CONCLUSION: Results did not provide evidence of an association between breast cancer and drinking water contaminated by wastewater. The computer mapping methods used in this study to link routine measurements required by the Safe Drinking Water Act with interview data can enhance individual-level epidemiologic studies of multiple health outcomes, including diseases with substantial latency.

Aged↗

PubMed2006

A comparison of maternal interview and medical record ascertainment of violence among women who had poor pregnancy outcomes.

OBJECTIVES: This study investigated the agreement between self-reported and medical record assessment of exposure to violence and the impact of misclassification on the estimation of the association between exposure to violence and infant death and very low birthweight. METHODS: The study population consisted of women who participated in two case-control studies on infant death and very low birthweight. There were 254 pairs of interviews and medical record reviews available for comparison. RESULTS: A total of 153 women (60.2%) reported ever being exposed to violence--92 (60.1%) based on the interview only, 18 (11.8%) based on the medical record only, and 43 (28.1%) in both sources. The sensitivity of the violence variables was low, ranging from 16.9% to 31.9% and kappa statistics showed poor agreement. Lower rates of all types of violence were found through the medical record than through the interview. CONCLUSION: Prevalence of violence based on medical record alone had a high degree of misclassification and some odds ratios were biased toward the null. Studies in which violence is an exposure, outcome, or confounder must use participant interviews in order to gather accurate information. A combination of sources may be the most accurate.

Adult↗

PubMed2006

Method for mapping population-based case-control studies: an application using generalized additive models.

BACKGROUND: Mapping spatial distributions of disease occurrence and risk can serve as a useful tool for identifying exposures of public health concern. Disease registry data are often mapped by town or county of diagnosis and contain limited data on covariates. These maps often possess poor spatial resolution, the potential for spatial confounding, and the inability to consider latency. Population-based case-control studies can provide detailed information on residential history and covariates. RESULTS: Generalized additive models (GAMs) provide a useful framework for mapping point-based epidemiologic data. Smoothing on location while controlling for covariates produces adjusted maps. We generate maps of odds ratios using the entire study area as a reference. We smooth using a locally weighted regression smoother (loess), a method that combines the advantages of nearest neighbor and kernel methods. We choose an optimal degree of smoothing by minimizing Akaike's Information Criterion. We use a deviance-based test to assess the overall importance of location in the model and pointwise permutation tests to locate regions of significantly increased or decreased risk. The method is illustrated with synthetic data and data from a population-based case-control study, using S-Plus and ArcView software. CONCLUSION: Our goal is to develop practical methods for mapping population-based case-control and cohort studies. The method described here performs well for our synthetic data, reproducing important features of the data and adequately controlling the covariate. When applied to the population-based case-control data set, the method suggests spatial confounding and identifies statistically significant areas of increased and decreased odds ratios.

Case-Control Studies↗

PubMed2006

Departure from multiplicative interaction for catechol-O-methyltransferase genotype and active/passive exposure to tobacco smoke among women with breast cancer.

BACKGROUND: Women with homozygous polymorphic alleles of catechol-O-methyltransferase (COMT-LL) metabolize 2-hydroxylated estradiol, a suspected anticarcinogenic metabolite of estrogen, at a four-fold lower rate than women with no polymorphic alleles (COMT-HH) or heterozygous women (COMT-HL). We hypothesized that COMT-LL women exposed actively or passively to tobacco smoke would have higher exposure to 2-hydroxylated estradiol than never-active/never passive exposed women, and should therefore have a lower risk of breast cancer than women exposed to tobacco smoke or with higher COMT activity. METHODS: We used a case-only design to evaluate departure from multiplicative interaction between COMT genotype and smoking status. We identified 502 cases of invasive incident breast cancer and characterized COMT genotype. Information on tobacco use and other potential breast cancer risk factors were obtained by structured interviews. RESULTS: We observed moderate departure from multiplicative interaction for COMT-HL genotype and history of ever-active smoking (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 0.7, 3.8) and more pronounced departure for women who smoked 40 or more years (aOR = 2.3, 95% CI: 0.8, 7.0). We observed considerable departure from multiplicative interaction for COMT-HL genotype and history of ever-passive smoking (aOR = 2.0, 95% CI: 0.8, 5.2) or for having lived with a smoker after age 20 (aOR = 2.8, 95% CI: 0.8, 10). CONCLUSION: With greater control over potential misclassification errors and a large case-only population, we found evidence to support an interaction between COMT genotype and tobacco smoke exposure in breast cancer etiology.

Journal Article↗

PubMed2005

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.

Adult↗

PubMed2005

Spatial analysis of lung, colorectal, and breast cancer on Cape Cod: an application of generalized additive models to case-control data.

BACKGROUND: The availability of geographic information from cancer and birth defect registries has increased public demands for investigation of perceived disease clusters. Many neighborhood-level cluster investigations are methodologically problematic, while maps made from registry data often ignore latency and many known risk factors. Population-based case-control and cohort studies provide a stronger foundation for spatial epidemiology because potential confounders and disease latency can be addressed. METHODS: We investigated the association between residence and colorectal, lung, and breast cancer on upper Cape Cod, Massachusetts (USA) using extensive data on covariates and residential history from two case-control studies for 1983-1993. We generated maps using generalized additive models, smoothing on longitude and latitude while adjusting for covariates. The resulting continuous surface estimates disease rates relative to the whole study area. We used permutation tests to examine the overall importance of location in the model and identify areas of increased and decreased risk. RESULTS: Maps of colorectal cancer were relatively flat. Assuming 15 years of latency, lung cancer was significantly elevated just northeast of the Massachusetts Military Reservation, although the result did not hold when we restricted to residences of longest duration. Earlier non-spatial epidemiology had found a weak association between lung cancer and proximity to gun and mortar positions on the reservation. Breast cancer hot spots tended to increase in magnitude as we increased latency and adjusted for covariates, indicating that confounders were partly hiding these areas. Significant breast cancer hot spots were located near known groundwater plumes and the Massachusetts Military Reservation. DISCUSSION: Spatial epidemiology of population-based case-control studies addresses many methodological criticisms of cluster studies and generates new exposure hypotheses. Our results provide evidence for spatial clustering of breast cancer on upper Cape Cod. The analysis suggests further investigation of the potential association between breast cancer and pollution plumes based on detailed exposure modeling.

Adult↗

PubMed2005

A case-only analysis of the interaction between N-acetyltransferase 2 haplotypes and tobacco smoke in breast cancer etiology.

INTRODUCTION: N-acetyltransferase 2 is a polymorphic enzyme in humans. Women who possess homozygous polymorphic alleles have a slower rate of metabolic activation of aryl aromatic amines, one of the constituents of tobacco smoke that has been identified as carcinogenic. We hypothesized that women with breast cancer who were slow acetylators would be at increased risk of breast cancer associated with active and passive exposure to tobacco smoke. METHODS: We used a case-only study design to evaluate departure from multiplicativity between acetylation status and smoking status. We extracted DNA from buccal cell samples collected from 502 women with incident primary breast cancer and assigned acetylation status by genotyping ten single-nucleotide polymorphisms. Information on tobacco use and breast cancer risk factors was obtained by structured interviews. RESULTS: We observed no substantial departure from multiplicativity between acetylation status and history of ever having been an active smoking (adjusted odds ratio estimate of departure from multiplicativity = 0.9, 95% confidence interval 0.5 to 1.7) or ever having had passive residential exposure to tobacco smoke (adjusted odds ratio = 0.7, 95% confidence interval 0.4 to 1.5). The estimates for departure from multiplicativity between acetylation status and various measures of intensity, duration, and timing of active and passive tobacco exposure lacked consistency and were generally not supportive of the idea of a gene-environment interaction. CONCLUSION: In this, the largest case-only study to evaluate the interaction between acetylation status and active or passive exposure to tobacco smoke, we found little evidence to support the idea of a departure from multiplicativity.

Acetylation↗

PubMed2005

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 > 50th and >75th percentile when shorter latency periods were considered, and for exposures < 50th and >90th 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.

Adult↗

PubMed2004

Association between residence on Cape Cod, Massachusetts, and breast cancer.

PURPOSE: Massachusetts cancer registry and case-control data suggest that breast cancer incidence is elevated on Cape Cod relative to other parts of the state. We examined the association between length of residence on Cape Cod and breast cancer, since residential history could be acting as a surrogate for unidentified environmental risk factors. METHODS: We computed odds ratios (OR) and 95% confidence limits (CL) for 1121 cases occurring between 1988 and 1995 on Cape Cod and 992 controls, according to categories of residence time on Cape Cod, after adjusting for age, family history, parity and age at first live or stillbirth, education, body mass index, and breast cancer history. RESULTS: Breast cancer risk was elevated among women living on Cape Cod 5 or more years with a peak occurring in the 25 to less than 30 year category (adjusted OR=1.72; 95% CL, 1.12, 2.64). Adjusting for confounding strengthened the associations. Odds ratios did not increase monotonically over categories of longer residence. CONCLUSIONS: Our results suggest that longer residence on Cape Cod is associated with elevated breast cancer risk, however inconsistency in the pattern of association limits conclusions that might be drawn about it. Suspected environmental exposures include pesticides and drinking water contaminated by industrial, agricultural, and residential land use.

Adult↗

PubMed2004

Breast cancer risk and historical exposure to pesticides from wide-area applications assessed with GIS.

Pesticides are of interest in etiologic studies of breast cancer because many mimic estrogen, a known breast cancer risk factor, or cause mammary tumors in animals, but most previous studies have been limited by using one-time tissue measurements of residues of only a few pesticides long banned in the United States. As an alternative method to assess historical exposures to banned and current-use pesticides, we used geographic information system (GIS) technology in a population-based case-control study of 1,165 women residing in Cape Cod, Massachusetts, who were diagnosed with breast cancer in 1988-1995 and 1,006 controls. We assessed exposures dating back to 1948 (when DDT was first used there) from pesticides applied for tree pests (e.g., gypsy moths), cranberry bogs, other agriculture, and mosquito control on wetlands. We found no overall pattern of association between pesticide use and breast cancer. We found modest increases in risk associated with aerial application of persistent pesticides on cranberry bogs and less persistent pesticides applied for tree pests or agriculture. Adjusted odds ratios for these exposures were 1.8 or lower, and, with a few exceptions, confidence intervals did not exclude the null. The study is limited by uncertainty about locations of home addresses (particularly before 1980) and unrecorded tree pest and mosquito control events as well as lack of information about exposures during years when women in the study lived off Cape Cod and about women with potentially important early life exposures on Cape Cod who were not included because they moved away.

Aged↗

PubMed2003

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.

Adolescent↗

PubMed2002

A null association between active or passive cigarette smoking and breast cancer risk.

The effect of smoking on breast cancer risk has been null in large, well-conducted cohort studies. In a previous study, we stratified the population into active smokers, passive smokers, and never-active never-passive smokers and modeled early life cigarette smoke exposures as causal and later life cigarette smoke exposure as preventive. We observed a complex association between cigarette smoke and breast cancer risk. Using a similar design and population, this study did not confirm the earlier result. Neither ever-active smoking (adjusted odds ratio (OR) = 0.72, 95% confidence intervals (CI) 0.55-0.95) nor ever-passive smoking (adjusted OR = 0.85, 95% CI 0.63-1.1) were strongly associated with breast cancer risk compared with never-active never-passive smoking. No patterns of effects were observed in subgroup analyses.

Breast Neoplasms↗

PubMed2002

A method for spatial analysis of risk in a population-based case-control study.

Spatial distributions of disease occurrence and risk have traditionally served as a tool for identifying exposures of public health concern. Current software for manipulating geographic data (GIS) now allows many kinds of analyses not feasible before. This paper presents a method for producing a "picture" of disease risks based on residential history data from a population based case-control study. We illustrate the method using geographically coded data on individual-level risk factors, such as age and smoking, from a cancer study of the Upper Cape Cod region of Massachusetts for 1983-1986. Our results show the association between lung cancer and residential location as an indicator of exposure. Crude and adjusted odds ratios were estimated by adaptive rate stabilization and mapped using kriging as an interpolation method to examine the risk of lung cancer in the region. The crude and adjusted surfaces for various smoothing parameters were compared to identify areas of increased lung cancer not explained by standard risk factors. Such spatial patterns of disease risk may provide clues to exposures of importance or confirm associations with previously suspected exposures.

Adult↗

PubMed2002

Exploring associations between residential location and breast cancer incidence in a case-control study.

Locating geographic hot spots of cancer may lead to new causal hypotheses and ultimately to new knowledge of cancer-causing factors. The Cape Cod region of Massachusetts has experienced elevated incidence of breast cancer compared with statewide averages. The origins of the excess remain largely unexplained, even after the Upper Cape Cod Cancer Incidence Study investigated numerous potential environmental exposures. Using case-control data from this study (258 cases and 686 controls), we developed an exploratory approach for measuring associations between residential location and breast cancer incidence, adjusting for individual-level risk factors. We measured crude and adjusted odds ratios over the study region using fixed-scale grids and a smoothing algorithm of overlapping circular units. Polycircular hot spot regions, derived from the peak values of the smoothed odds ratios, delineated geographic areas wherein residence was associated with 60% [odds ratio (OR), 1.6; 95% confidence interval (CI), 0.8-3.2] to 210% (OR, 3.1; 95% CI, 1.3-7.2) increased incidence relative to the remainder of the study population. The findings suggest several directions for further research, including the identification of potential environmental exposures that may be assessed in forthcoming case-control studies.

Adolescent↗

PubMed2000

Alcohol Drinking and Risk of Breast Cancer.

Using a case-control design, the authors studied female residents of five Massachusetts towns between 1983 and 1986. The objective was to measure the association between breast cancer occurrence and drinking alcohol. Cohort and case-control studies have often observed an association between drinking alcohol and breast cancer risk. In this study, women with any history of drinking alcohol had a risk of breast cancer 1.2-fold greater than women who never drank alcohol (95% confidence interval 0.7-1.8). The relative risk of breast cancer did not depend on the usual number of drinks per day or drinking history relative to time of diagnosis. Women who reported ever having a period of 6 months or more during which they drank more than average had an adjusted relative risk of breast cancer equal to 2.6 (95% confidence interval 1.1-5.8). The estimates of effect are consistent with the positive dose-response trends reported in a pooled analysis of large cohort studies and a meta-analysis of a broader spectrum of studies. Alcohol drinking remains one of the few risk factors for breast cancer amenable to intervention.

Journal Article↗