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Biomedical subjects

Matthew R Bonner

Publications and source records attributed to Matthew R Bonner.

At least 19 recordsLinked to original sources

Lifetime adult weight gain, central adiposity, and the risk of pre- and postmenopausal breast cancer in the Western New York exposures and breast cancer study.

While there are quite consistent data regarding associations of body weight and postmenopausal breast cancer, there are now accumulating data that would indicate that weight gain in adult life is more predictive of risk than absolute body weight. There is, however, little known about the relative impact of timing of weight gain in adult life as well as other characteristics of the weight and breast cancer association that might provide insight into the mechanism of the observation. We conducted a population-based case control study of breast cancer (1996-2001), the Western New York Exposures and Breast Cancer Study. Included were 1,166 women with primary, histologically confirmed, incident breast cancer and 2,105 controls frequency-matched on age, race and county of residence. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. We found increased risk of breast cancer associated with lifetime adult weight gain among post- but not premenopausal women, and there was a 4% increase in risk for each 5 kg increase in adult weight. Further there was a tendency toward a stronger association for those with higher waist circumference and those with positive estrogen or progesterone status, and who had never used HRT. We also found an association with risk for weight gain since first pregnancy and for weight gain between the time of the first pregnancy and menopause, independent of body mass index and lifetime adult weight gain. Our results suggest that there are time periods of weight gain that have greater impact on risk, and that central body fat, receptor status and hormone replacement therapy may all affect the observed association.

Adiposity↗

Lifetime cumulative exposure to secondhand smoke and risk of myocardial infarction in never smokers: results from the Western New York health study, 1995-2001.

BACKGROUND: Although many epidemiologic studies have investigated the association between exposure to secondhand smoke (SHS) and risk of coronary heart disease (CHD), few of these studies have assessed exposure measures from different sources over a lifetime. Therefore, we sought to test the association between lifetime cumulative exposure to SHS and risk of myocardial infarction (MI) (as an indication of CHD) among never smokers. METHODS: A population-based case-control study in which participants were 1541 never smokers (284 cases and 1257 controls) drawn from 1197 women and men with incident MI and 2850 healthy controls (aged 35-70 years) identified from 2 Western New York counties between 1995 and 2001. Study subjects were asked to report their exposure to SHS at home, at work, and in public settings from childhood to their present age. Exposure histories from each source were combined to form a cumulative lifetime exposure measure. Multiple logistic regression analysis estimated the association between SHS exposure and case status adjusted for age, sex, education, body mass index, race, drinking status, lifetime physical activity, hypertension, diabetes mellitus, and hypercholesterolemia. RESULTS: After adjustment for covariates, exposure to SHS was not significantly associated with an increased risk of MI. Compared with participants in the bottom tertile of SHS exposure, those in the top tertile had an odds ratio of 1.19 [95% confidence interval, 0.78-1.82] for MI. Virtually all subjects reported some exposure to SHS over their lifetime, but self-reported exposures declined over time, especially in the period closest to the interview. CONCLUSIONS: Exposure to SHS has declined sharply among nonsmokers in recent years. In the absence of high levels of recent exposure to SHS, cumulative lifetime exposure to SHS may not be as important a risk factor for MI as previously thought.

Adult↗

Radon, secondhand smoke, glutathione-S-transferase M1 and lung cancer among women.

Tobacco smoke and ionizing radiation induce oxidative stress by transmitting or generating reactive oxygen species (ROS). We hypothesized that glutathione-S-transferase M1 (GSTM1) null homozygotes would have decreased ability to neutralize ROS that might increase their susceptibility to lung cancer. A case-only design was used with lung cancer cases pooled from 3 previously completed case-control studies using archival tissue samples from 270 lung cancer cases to genotype GSTM1. Radon concentrations were measured with long-term alpha-track radon detectors. Secondhand smoke (SHS) was measured with questionnaires and interviews. Unconditional logistic regression was used to calculate the interaction odds ratios (OR) and 95% confidence intervals (95% CI). Radon concentrations >121 Bq m(-3) were associated with a >3-fold interaction OR (OR = 3.41; 95% CI = 1.10, 10.61) for GSTM1 null homozygotes compared to GSTM1 carriers; the linear trend was significant (p trend = 0.03). The SHS and GSTM1 interaction OR was also elevated (OR = 2.28; 95% CI = 1.15-4.51) among never-smokers. This may be the first study to provide evidence of a GSTM1 and radon interaction in risk of lung cancer. Additionally, these findings support the hypothesis that radon and SHS promote neoplasia through shared elements of a common pathway.

Aged↗

Ten years of clinical experience with adult meningitis at an urban academic medical center.

The purpose of this study is to describe the clinical presentation and bacteriology of adult patients admitted to an urban academic medical center with bacterial meningitis over a 10-year period. In this retrospective review, we identified all adult patients discharged from a tertiary care facility between November 1992 and March 2003 with a diagnosis of bacterial meningitis. Data regarding demographics, vital signs, presenting symptoms, seven predisposing factors, body fluid cultures, cerebrospinal fluid (CSF) findings, and mortality were abstracted. Data were analyzed using descriptive methods. We identified 38 cases. Overall mortality rate was 18.4% (95% confidence interval 7.7-34.3%). The most common of the seven predisposing factors was an immunocompromised state (31.6%). Streptococcus pneumoniae (24.3%), other streptococcus species (24.3%), and Gram-negative rods (16.2%) were the most commonly identified organisms. The classic meningitis triad (fever, neck stiffness, mental status change or headache) was present in only 21.1% of cases. CSF analysis demonstrated WBC >or= 100/mm3 in 81.3%, decreased glucose (< 50 mg/dL) in 50%, and elevated protein (> 45 mg/dL) in 91.2%. With increasing numbers of immunocompromised patients, atypical presentations of bacterial meningitis seem to be more common. A higher percentage of bacterial meningitis cases seem to be caused by Gram-negative rods and Streptococcus species other than Streptococcus pneumoniae. The classic meningitis triad occurred in fewer cases than previously described.

Academic Medical Centers↗

Pendimethalin exposure and cancer incidence among pesticide applicators.

BACKGROUND: Pendimethalin, a widely used herbicide, has been classified as a group C possible human carcinogen by the U.S. Environmental Protection Agency. We evaluated the incidence of cancer in relation to reported pendimethelin use among pesticide applicators in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. METHODS: Information on pesticide use came from two questionnaires (enrollment and take-home). The present analysis includes 9089 pendimethalin-exposed and 15,285 nonpendimethalin-exposed pesticide applicators with complete information on pendimethalin use and covariates from a take-home questionnaire. We conducted Poisson regression analyses to evaluate the association of pendimethalin exposure with cancer incidence (mean follow-up = 7.5 years) using two exposure metrics: tertiles of lifetime days of exposure and tertiles of intensity-weighted lifetime days of exposure. RESULTS: Overall cancer incidence did not increase with increasing lifetime pendimethalin use, and there was no clear evidence of an association between pendimethalin use and risks for specific cancers. The risk for rectal cancer rose with increasing lifetime pendimethalin exposure when using nonexposed as the reference (rate ratio = 4.3; 95% confidence interval = 1.5-12.7 for the highest exposed subjects; P for trend = 0.007), but the association was attenuated when using the low exposed as the referent group (P for trend = 0.08). Similar patterns for rectal cancer were observed when using intensity-weighted exposure-days. The number of rectal cancer cases among the pendimethalin-exposed was small (n = 19). There was some evidence for an elevated risk for lung cancer, but the excess occurred only in the highest exposure category for lifetime pendimethalin exposure. The trends for lung cancer risk were inconsistent for different exposure metrics. CONCLUSIONS: We did not find a clear association of lifetime pendimethalin exposure either with overall cancer incidence or with specific cancer sites.

Adult↗

Phorate exposure and incidence of cancer in the agricultural health study.

BACKGROUND: We recently reported a link between use of the organophosphate pesticide phorate and risk of prostate cancer among applicators with a family history of prostate cancer in the Agricultural Health Study (AHS). OBJECTIVE: This finding, together with findings of associations between other organophosphate pesticides and cancer more broadly, prompted us to examine phorate exposure and overall cancer incidence in the AHS. Adding 3 years of follow-up and using more detailed exposure information allowed us to see whether the prostate cancer finding held. METHODS: The AHS is a prospective study of licensed restricted-use pesticide applicators from North Carolina and Iowa. To our knowledge, this is the largest examination of workers occupationally exposed to phorate. Pesticide exposure and other information was collected using two self-administered questionnaires completed from 1993 to 1997. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CI), adjusting for potential confounders. RESULTS: Phorate use was not related to the incidence of all cancers combined or to any individual cancer, although we had insufficient numbers to study non-Hodgkin lymphoma or leukemia, which have been linked to organophosphates in other studies. Although prostate cancer risk was not significantly related to phorate use overall or among those without a family history, the risk tended to increase among applicators with a family history of prostate cancer. The interaction RR was 1.53 (95% CI, 0.99-2.37). CONCLUSION: The observed statistical interaction suggests a gene-environment interaction between family history and phorate exposure in the incidence of prostate cancer, but other explanations are also possible.

Adult↗

Cancer incidence among male pesticide applicators in the Agricultural Health Study cohort exposed to diazinon.

Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993-1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans.

Adult↗

Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China.

The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR = 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19-0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR = 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs.

Adult↗

Assessing spatio-temporal variability of risk surfaces using residential history data in a case control study of breast cancer.

BACKGROUND: Most analyses of spatial clustering of disease have been based on either residence at the time of diagnosis or current residence. An underlying assumption in these analyses is that residence can be used as a proxy for environmental exposure. However, exposures earlier in life and not just those in the most recent period may be of significance. In breast cancer, there is accumulating evidence that early life exposures may contribute to risk. We explored spatio-temporal patterns of risk surfaces using data on lifetime residential history in a case control study of breast cancer, and identified elevated areas of risk and areas potentially having more exposure opportunities, defined as risk surfaces in this study. This approach may be more relevant in understanding the environmental etiology of breast cancer, since lifetime cumulative exposures or exposures at critical times may be more strongly associated with risk for breast cancer than exposures from the recent period. RESULTS: A GIS-based exploratory spatial analysis was applied, and spatio-temporal variability of those risk surfaces was evaluated using the standardized difference in density surfaces between cases and controls. The significance of the resulting risk surfaces was tested and reported as p-values. These surfaces were compared for premenopausal and postmenopausal women, and were obtained for each decade, from the 1940s to 1990s. We found strong evidence of clustering of lifetime residence for premenopausal women (for cases relative to controls), and a less strong suggestion of such clustering for postmenopausal women, and identified a substantial degree of temporal variability of the risk surfaces. CONCLUSION: We were able to pinpoint geographic areas with higher risk through exploratory spatial analyses, and to assess temporal variability of the risk surfaces, thus providing a working hypothesis on breast cancer and environmental exposures. Geographic areas with higher case densities need further epidemiologic investigation for potential relationships between lifetime environmental exposures and breast cancer risk. Examination of lifetime residential history provided additional information on geographic areas associated with higher risk; limiting exploration of chronic disease clustering to current residence may neglect important relationships between location and disease.

Journal Article↗

Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer.

Experimental evidence suggests that green tea (Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epidemiologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR)=4.93; 95% confidence interval (95% CI)=1.27-19.13) than for drinkers (OR=1.88; 95% CI=1.01-3.48). Further, among individuals with the OGG1 Cys(326) allele, daily consumption was associated with a 72% reduction (95% CI=0.09-0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Ser(326) homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage.

Alcohol Oxidoreductases↗

Secondhand smoke exposure in early life and the risk of breast cancer among never smokers (United States).

Evidence is increasing that some early life exposures affect breast cancer risk. Exposure to secondhand smoke (SHS) during childhood may be one such exposure. As part of the WEB Study (Western New York Exposures and Breast Cancer Study), we conducted a population-based, case-control study with 1166 women aged 35 to 79 diagnosed with histologically confirmed, primary, incident breast cancer. Controls (n = 2105) were randomly selected from the Department of Motor Vehicles driver's license list (< or =age 65) and the Center for Medicare & Medicaid Services rolls (> age 65). Participants were queried regarding household and workplace SHS exposure. Person-years of lifetime cumulative SHS exposure were computed as well as cumulative exposure up to 21 years of age. Unconditional logistic regression adjusting for potential confounders was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Lifetime cumulative exposure to household SHS was not associated with an increase in breast cancer risk for premenopausal (OR = 1.17, 95% CI = 0.54-2.56) or postmenopausal (OR = 1.29; 95% CI = 0.82-2.01) women. Neither was risk increased among women exposed to SHS before the age of 21 or at the time of birth, menarche, or a women's first birth. In this study, exposure to SHS either in adult or early life does not appear to be associated with the risk of breast cancer.

Adult↗

Smoky coal exposure, NBS1 polymorphisms, p53 protein accumulation, and lung cancer risk in Xuan Wei, China.

Lung cancer rates in Xuan Wei County are among the highest in China and have been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons (PAHs). The NBS1 gene product participates in DNA double-strand break repair and DNA damage-induced checkpoint activation, which are critical for maintaining genomic integrity. The p53 tumor suppressor gene is known to play key roles both in the maintenance of genomic stability in mammalian cells and in DNA damage surveillance. We examined the association between two common NBS1 polymorphisms (Leu34Leu, Gln185Glu) and lung cancer risk in a population-based case-control study in Xuan Wei, China. Individuals homozygous for the NBS1 34Leu or NBS1 185Glu variants were found to have an increased risk of lung cancer (odds ratio [OR] 2.15, 95% confidence interval [CI]: 0.91-5.10 and OR 2.53, 95% CI: 1.05-6.08, respectively). A haplotype containing the variant alleles from both NBS1 SNPs was associated with increased risk of lung cancer compared with the most common haplotype. Further, the associations were particularly pronounced among cases with over expression of p53 protein. These results suggest that NBS1 could be important in the pathogenesis of lung cancer in this population. However, additional studies in other populations with substantial environmental exposures to PAHs are needed to confirm our findings.

Adult↗

Pesticides and human cancers.

The potential for human carcinogenicity of almost all pesticides currently on the market has been poorly evaluated and is inadequately understood. Generating mechanistic data in both animal studies and epidemiology will play an increasingly important role in the future. Improved exposure assessment, in large prospective studies that generate reliable exposure-response data that focus on individual pesticide exposures are needed. One of the greatest opportunities to make more rapid progress will be to foster more multi-disciplinary collaborations between toxicologists and epidemiologists. Collaborations on molecular epidemiology investigations offers such opportunities to both toxicologists and epidemiologists that were not possible even a decade ago.

Animals↗

Positional accuracy of two methods of geocoding.

BACKGROUND: Geocoding is often used in epidemiologic studies to map residences with geographic information systems (GIS). The accuracy of the method is usually not determined. METHODS: We collected global positioning system (GPS) measurements at homes in a case-control study of non-Hodgkin lymphoma in Iowa. We geocoded the addresses by 2 methods: (1) in-house, using ArcView 3.2 software and the U.S. Census Bureau TIGER 2000 street database; and (2) automated geocoding by a commercial firm. We calculated the distance between the geocoded and GPS location (positional error) overall and separately for homes within towns and outside (rural). We evaluated the error in classifying homes with respect to their proximity to crop fields. RESULTS: Overall, the majority of homes were geocoded with positional errors of less than 100 m by both methods (ArcView/TIGER 2000, median = 62 m [interquartile range = 39-103]; commercial firm, median = 61 m [interquartile range = 35-137]). For town residences, the percent geocoded with errors of </=100 m was 81% for ArcView/TIGER 2000 and 84% for the commercial firm. For rural residences, a smaller percent of addresses were geocoded with this level of accuracy, especially by the commercial firm (ArcView/TIGER 2000, 56%; commercial firm, 28%). Geocoding errors affected our classification of homes according to their proximity to agricultural fields at 100 m, but not at greater distances (250-500 m). CONCLUSIONS: Our results indicate greater positional errors for rural addresses compared with town addresses. Using a commercial firm did not improve accuracy compared with our in-house method. The effect of geocoding errors on exposure classification will depend on the spatial variation of the exposure being studied.

Adult↗

Occupational exposure to carbofuran and the incidence of cancer in the Agricultural Health Study.

Carbofuran is a carbamate insecticide registered for use on a variety of food crops including corn, alfalfa, rice, and tobacco. An estimated 5 million pounds of carbofuran is used annually in the United States, and 45% of urban African-American women have detectable levels of carbofuran in their plasma. Nitrosated carbofuran has demonstrated mutagenic properties. We examined exposure to carbofuran and several tumor sites among 49,877 licensed pesticide applicators from Iowa and North Carolina enrolled in the Agricultural Health Study. We obtained information regarding years of use, frequency of use in an average year, and when use began for 22 pesticides using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CIs) adjusting for potential confounders. Lung cancer risk was 3-fold higher for those with > 109 days of lifetime exposure to carbofuran (RR = 3.05; 95% CI, 0.94-9.87) compared with those with < 9 lifetime exposure days, with a significant dose-response trend for both days of use per year and total years of use. However, carbofuran use was not associated with lung cancer risk when nonexposed persons were used as the referent. In addition, carbofuran exposure was not associated with any other cancer site examined. Although carbamate pesticides are suspected human carcinogens, these results should be interpreted cautiously because there was no a priori hypothesis specifically linking carbofuran to lung cancer.

Adult↗

Breast cancer risk and exposure in early life to polycyclic aromatic hydrocarbons using total suspended particulates as a proxy measure.

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous in the environment. We hypothesized that early life exposure to PAHs may have particular importance in the etiology of breast cancer. We conducted a population-based, case-control study of ambient exposure to PAHs in early life in relation to the risk of breast cancer. Total suspended particulates (TSP), a measure of ambient air pollution, was used as a proxy for PAHs exposure. Cases (n = 1,166) were women with histologically confirmed, primary, incident breast cancer. Controls (n = 2,105) were frequency matched by age, race, and county of residence to cases. Annual average TSP concentrations (1959-1997) by location were obtained from the New York State Department of Environmental Conservation for Erie and Niagara Counties. Based on the monitor readings, prediction maps of TSP concentrations were generated with ArcGIS 8.0 (ESRI, Inc., Redlands, CA) using inverse distance squared weighted interpolation. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. In postmenopausal women, exposure to high concentrations of TSP (>140 microg/m(3)) at birth was associated with an adjusted odds ratio of 2.42 (95% confidence interval, 0.97-6.09) compared with exposure to low concentrations (<84 microg/m(3)). However, in premenopausal women, where exposures were generally lower, the results were inconsistent with our hypothesis and in some instances were suggestive of a reduction in the risk of breast cancer. Our study suggests that exposure in early life to high levels of PAHs may increase the risk of postmenopausal breast cancer; however, other confounders related to geography cannot be ruled out.

Adult↗