Matthew R. Bonner

Positional Accuracy of Geocoded Addresses in Epidemiologic Research

Background Geographic information systems (GIS) offer powerful techniques for epidemiologists. Geocoding is an important step in the use of GIS in epidemiologic research, and the validity of epidemiologic studies using this methodology depends, in part, on the positional accuracy of the geocoding process. Methods We conducted a study comparing the validity of positions geocoded with a commercially available program to positions determined by Global Positioning System (GPS) satellite receivers. Addresses (N = 200) were randomly selected from a recently completed case–control study in Western New York State. We geocoded addresses using ArcView 3.2 on the GDT Dynamap/2000 U.S. Street database. In addition, we measured the longitude and latitude of these addresses with a GPS receiver. The distance between the locations obtained by these two methods was calculated for all addresses. Results The distance between the geocoded point and the GPS point was within 100 m for the majority of subject addresses (79%), with only a small proportion (3%) having a distance greater than 800 m. The overall median distance between GPS points and geocoded points was 38 m (90% confidence interval [CI] = 34–46). Distances were not different for cases and controls. Urban addresses (median = 32 m; CI = 28–37) were slightly more accurate than nonurban addresses (median = 52 m; CI = 44–61). Conclusions. This study indicates that the suitability of geocoding for epidemiologic research depends on the level of spatial resolution required to assess exposure. Although sources of error in positional accuracy for geocoded addresses exist, geocoding of addresses is, for the most part, very accurate.

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 TIGER2000 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.

Increased Cancer Burden Among Pesticide Applicators and Others Due to Pesticide Exposure

A growing number of well‐designed epidemiological and molecular studies provide substantial evidence that the pesticides used in agricultural, commercial, and home and garden applications are associated with excess cancer risk. This risk is associated both with those applying the pesticide and, under some conditions, those who are simply bystanders to the application. In this article, the epidemiological, molecular biology, and toxicological evidence emerging from recent literature assessing the link between specific pesticides and several cancers including prostate cancer, non‐Hodgkin lymphoma, leukemia, multiple myeloma, and breast cancer are integrated. Although the review is not exhaustive in its scope or depth, the literature does strongly suggest that the public health problem is real. If we are to avoid the introduction of harmful chemicals into the environment in the future, the integrated efforts of molecular biology, pesticide toxicology, and epidemiology are needed to help identify the human carcinogens and thereby improve our understanding of human carcinogenicity and reduce cancer risk. CA Cancer J Clin 2013;.

Occupational Pesticide Exposures and Cancer Risk: A Review

A review of the epidemiological literature linking pesticides to cancers in occupational studies worldwide was conducted, with particular focus on those articles published after the release of IARC Monograph 53 (1991): Occupational Exposures in Insecticide Applications and Some Pesticides. Important new data are now available. Chemicals in every major functional class of pesticides including insecticides, herbicide, fungicides, and fumigants have been observed to have significant associations with an array of cancer sites. Moreover, associations were observed with specific chemicals in many chemical classes of pesticides such as chlorinated, organophosphate, and carbamate insecticides and phenoxy acid and triazine herbicides. However, not every chemical in these classes was found to be carcinogenic in humans. Twenty-one pesticides identified subsequent to the last IARC review showed significant exposure-response associations in studies of specific cancers while controlling for major potential confounders. This list is not an exhaustive review and many of these observations need to be evaluated in other epidemiological studies and in conjunction with data from toxicology and cancer biology. Nonetheless, it is reasonable and timely for the scientific community to provide a multidisciplinary expert review and evaluation of these pesticides and their potential to produce cancer in occupational settings.

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.

A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma

Mitochondrial DNA (mtDNA) copy number is increased in patients with chronic lymphocytic leukemia (CLL), in Burkitt lymphoma and Epstein-Barr virus-transformed lymphoblastoid cell lines, and in T cells activated via the T-cell receptor. We hypothesized that having a higher mtDNA copy number in peripheral white blood cell DNA from healthy subjects would be associated with future risk of non-Hodgkin lymphoma (NHL). We analyzed mtDNA copy number in 104 incident male NHL cases and 104 matched controls within the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention cohort. There was a dose-response relationship between tertiles of mtDNA copy number and risk of NHL (odds ratio [OR], 95% confidence interval [CI]: 1.0; 1.4 [0.7-2.8]; and 2.4 [1.0-5.5], respectively; P(trend) = .046). The effect was most pronounced for the CLL/small lymphocytic lymphoma (SLL) subtype (OR: 1.0; 3.2 [0.7-15.7]; 14.1 [1.9-103.2]; P(trend) = .009). These results suggest that mtDNA copy number could be associated with the risk of NHL, particularly CLL/SLL.

Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study

Background Permethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens. Objective In this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS). Methods A total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993–1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure. Results We found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76–11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41–10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups. Conclusions This study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation.

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.

Biomarkers of Chlorpyrifos Exposure and Effect in Egyptian Cotton Field Workers

Background Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for CPF exposure, whereas blood ChE activity is considered an indicator of CPF toxicity. However, whether these biomarkers are dose related has not been studied extensively in populations with repeated daily OP exposures. Objective We sought to determine the relationship between blood ChE and urinary TCPy during repeated occupational exposures to CPF. Methods Daily urine samples and weekly blood samples were collected from pesticide workers (n = 38) in Menoufia Governorate, Egypt, before, during, and after 9–17 consecutive days of CPF application to cotton fields. We compared blood butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities with the respective urinary TCPy concentrations in each worker. Results Average TCPy levels during the middle of a 1- to 2-week CPF application period were significantly higher in pesticide applicators (6,437 μg/g creatinine) than in technicians (184 μg/g) and engineers (157 μg/g), both of whom are involved in supervising the application process. We observed a statistically significant inverse correlation between urinary TCPy and blood BuChE and AChE activities. The no-effect level (or inflection point) of the exposure–effect relationships has an average urinary TCPy level of 114 μg/g creatinine for BuChE and 3,161 μg/g creatinine for AChE. Conclusions Our findings demonstrate a dose–effect relationship between urinary TCPy and both plasma BuChE and red blood cell AChE in humans exposed occupationally to CPF. These findings will contribute to future risk assessment efforts for CPF exposure.

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.