Papers by Michael Alavanja
PLOS ONE, 2015
Some studies suggest that telomere length (TL) may be influenced by environmental exposures, incl... more Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.
We performed both a laboratory and field intercomparison of two novel glass-based retrospective r... more We performed both a laboratory and field intercomparison of two novel glass-based retrospective radon detectors previously used in major radon case-control studies performed in Missouri and Iowa. The new detectors estimate retrospective residential radon exposure from the accumulation of a long-lived radon decay product, Pb-210, in glass. The detectors use track registration material in direct contact with glass surfaces to
Traditional methods for assessing radon exposure in epidemiological studies have used current amb... more Traditional methods for assessing radon exposure in epidemiological studies have used current ambient detector measurements as surrogates for concentrations decades ago in past residences occupied by study subjects. Substantial temporal and spatial variability has been found that challenges the validity of this practice. As an alternative, CR-39 surface monitors were attached to selected glass objects to measure alpha emissions from
Occupational and environmental medicine, Jan 6, 2015
Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to can... more Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. At enrolment (1993-1997), spouses provided information about ever use of specific pesticides, including 10 OPs, demographic information, reproductive health history and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% CIs for all cancers diagnosed through 2010 for North Carolina and through 2011 for Iowa. Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was assoc...
Journal of Occupational and Environmental Medicine
The Agricultural Health Study is a collaborative effort involving the National Cancer Institute, ... more The Agricultural Health Study is a collaborative effort involving the National Cancer Institute, the US Environmental Protection Agency, and the National Institute of Environmental Health Sciences. A goal of this investigation is to establish a large cohort of men and women that can be followed prospectively for 10 years or more to evaluate the role of agricultural exposures in the development of cancer, neurologic disease, reproductive difficulties, childhood developmental problems, and other chronic diseases. The study also will provide an opportunity to assess the role that diet, cooking methods, and other lifestyle factors have on the cause of cancer and other diseases. The cohort will be composed of approximately 112,000 adult study subjects, including 42,000 women, making this one of the largest cohorts of women ever assembled for an epidemiologic investigation of environmental and occupational exposures. Children of farm families also will be enrolled. The study will be condu...
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jan 30, 2015
Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HC... more Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC n=860, ICC n=260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; ptrend cups/day=<0.0001). More notable reduced risk was seen among women than m...
International Journal of Cancer, 2015
Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environme... more Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-7. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n=5701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular-cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular-cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors. This article is protected by copyright. All rights reserved.
International journal of epidemiology, Jan 6, 2015
Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed... more Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. Greater waist circumference (per 5 cm: HR = 1.04, 95% CI 1.03-1.05, P-value for trend = <0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05-1.09, P-value for trend = <0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status (P-value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI (P-value for interaction = <0.0001) varied by smoking status. Larger BMI was associated with higher ...
Nature communications, 2015
Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering gene... more Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering genetic variants that distinguish aggressive from nonaggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49 × 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 × 10(-8)). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85 × 10(-5)) with no association for nonaggressive prostate cancer compared with controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.
Occupational and environmental medicine, Jan 23, 2015
Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associat... more Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS. Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993-1997) and follow-up (1998-2005); cancer incidence was assessed through 2010(North Carolina)/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with ≥10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure). We observed elevated lung cancer risks (N=283) among applicators with the greatest number...
Cancer causes & control : CCC, 2000
The association between previous lung diseases (PLD) and lung cancer risk has not been studied ex... more The association between previous lung diseases (PLD) and lung cancer risk has not been studied extensively. We conducted a registry-based case-control study to examine the relation between previous lung diseases and lung cancer among women in Missouri. Incident cases (n = 676) were identified through the Missouri Cancer Registry for the period 1 January 1993 to 31 January 1994. Controls (n = 700) were selected through drivers' license files and Medicare files. Whether analyzing all respondents or in-person interviews only, elevated effect estimates were noted for several types of PLD. Elevated relative risk estimates were shown for chronic bronchitis (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.3), emphysema (OR = 2.7; 95% CI = 1.8-4.2), pneumonia (OR = 1.6; 95% CI = 1.2-2.0), and for all PLDs combined (OR = 1.5; 95% CI = 1.2-1.9). Analysis of only direct interviews did not show a substantial or consistent pattern of change in relative risk estimates. Because PLD...
Cancer research, Jan 15, 2000
Heterocyclic amines (HCAs) such as 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx), 2-amino-... more Heterocyclic amines (HCAs) such as 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx,), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are found in meats cooked at high temperatures. In rodents, MeIQx induces lung tumors. The purpose of this study was to investigate lung cancer risk posed by different HCAs in the diet. A population-based case-control study of 593 cases and 623 frequency-matched controls including both nonsmoking and smoking women was conducted in Missouri. An administered food frequency questionnaire with detailed questions on meat consumption, degrees of internal doneness, surface browning/charring, and cooking technique was linked to a database that provided exposure estimates of three HCAs. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. When comparing the 90th and 10th percentiles, significant excess risks were observed for MeIQx (OR...
Lung Cancer, 2001
Objecti6e: Some epidemiologic studies suggest that diets high in total fat, saturated fat, or cho... more Objecti6e: Some epidemiologic studies suggest that diets high in total fat, saturated fat, or cholesterol are associated with increased risk of lung cancer. Others suggest that diets high in red meat consumption, particularly well-done red meat, are a lung cancer risk factor. In Iowa, we had the opportunity to investigate concurrently the role of meat intake and macronutrients in lung cancer etiology. Methods: A population-based case-control study of both non-smoking and smoking women was conducted in Iowa. A 70-item food frequency questionnaire (FFQ) was completed by 360 cases and 574 frequency-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Multivariate models included age, education, pack-years of smoking, yellow-green vegetable intake, fruit/fruit juice intake, nutrient density calories, previous non-malignant lung disease, alcohol consumption and body mass index (BMI). Results: When comparing the fifth (highest) to the first (lowest) quintile of consumption of total fat, saturated fat and cholesterol, we obtained odds ratios of 2.0 (1.3-3.1), 3.0 (1.9-4.7), and 2.0 (1.3-3.0) respectively. However, when red meat was entered into the model along with total fat, saturated fat or cholesterol, the excess risk for the macronutrients disappeared while an odds ratio of 3.3 (1.7-7.6) was obtained for red meat. The odds ratios for red meat consumption were similar among adenocarcinoma cases, OR= 3.0 (1.1-7.9) and non-adenocarcinoma cases, OR = 3.2 (1.3-8.3) and among life-time nonsmokers and ex-smokers OR = 2.8 (1.4-5.4), and current smokers, OR = 4.9 (1.1-22.3). Yellow-green vegetables were protective with an odds ratio of 0.4 (0.2-0.7). Conclusions: Consumption of red meat, was associated with an increased risk of lung cancer even after controlling for total fat, saturated fat, cholesterol, fruit, yellow-green vegetable consumption and smoking history, while yellow-green vegetables are associated with a decreased risk of lung cancer.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014
Farming is often a family and multigenerational business. Relatedness among farmers could bias ge... more Farming is often a family and multigenerational business. Relatedness among farmers could bias gene-environment interaction analysis. To evaluate the potential relatedness of farmers, we used data from a nested case-control study of prostate cancer conducted in the Agricultural Health Study (AHS), a prospective study of farmers in Iowa and North Carolina. We analyzed the genetic data for 25,009 SNPs (single-nucleotide polymorphisms) from 2,220 White participants to test for cryptic relatedness among these farmers. We used two software packages: (i) PLINK, to calculate inbreeding coefficients and identity-by-descent (IBD) statistics and (ii) EIGENSOFT, to perform a principal component analysis on the genetic data. Inbreeding coefficients estimates and IBD statistics show that the subjects are overwhelmingly unrelated, with little potential for cryptic relatedness in these data. Our analysis rejects the hypothesis that individuals in the case-control study exhibit cryptic relatedness....
Occupational and environmental medicine, 2014
Exposure to allergens and microorganisms in the agricultural environment has been linked to alter... more Exposure to allergens and microorganisms in the agricultural environment has been linked to altered immune response. Studies in the general population have reported reduced risks of non-Hodgkin lymphoma (NHL) among those with a history of atopic conditions, although results are inconsistent. To evaluate the allergy-NHL association in the context of farm exposures, we conducted an investigation in the Agricultural Health Study, a prospective cohort of farmers and spouses from North Carolina and Iowa. Our study included 49 656 farmers and spouses with crop and animal exposures and allergy symptoms reported at baseline (1993-1997). We identified 418 incident cases of NHL (including chronic lymphocytic leukaemia and multiple myeloma) during follow-up through 2010 in North Carolina and 2011 in Iowa. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted proportional hazards models. At enrollment, over 80% of the study participants lived on farms...
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2015
Because of unique exposures, studies among farmers may yield insights into the relationship betwe... more Because of unique exposures, studies among farmers may yield insights into the relationship between allergies and non-Hodgkin lymphoid (NHL) neoplasms. We evaluated farm characteristics, allergic symptoms and conditions, and risk of NHL including specific subtypes in the Agricultural Health Study, a prospective cohort of farmers and spouses from North Carolina and Iowa. We identified 710 incident cases of NHL (including chronic lymphocytic leukemia and multiple myeloma) among 82,370 participants with baseline data on crop and animal exposures, including 454 cases among 52,850 participants with baseline data on recent allergy symptoms (rhinitis) and living on a farm during childhood. HR and 95% confidence intervals (CI) were calculated using multivariable-adjusted proportional hazards models. We observed reduced risks of NHL among farmers and spouses with rhinitis at baseline (HR, 0.63; 95% CI, 0.51-0.79), related to growing soybeans (HR, 0.80; 95% CI, 0.67-0.96), and among farmers w...
Occupational and environmental medicine, 2014
Farming and exposure to pesticides have been linked to non-Hodgkin lymphoma (NHL), and multiple m... more Farming and exposure to pesticides have been linked to non-Hodgkin lymphoma (NHL), and multiple myeloma (MM) in previous studies. We evaluated use of insecticides, fungicides and fumigants and risk of NHL, including MM and other NHL sub-types in the Agricultural Health Study, a US-based prospective cohort study. A total of 527 cases occurred among 55 875 pesticide applicators from enrollment (1993-1997) through 2011 in Iowa and 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and follow-up approximately five years later (1999-2005). Information from these questionnaires was used to create lifetime-days and intensity-weighted lifetime-days of pesticide use. Poisson regression and polytomous logit models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes including multiple myeloma, whil...
British Journal of Haematology, 2014
Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is associated with ... more Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1Á5 million participants (including 1388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index (BMI; HR = 1Á22, 95% CI: 1Á09-1Á35 per 5 kg/m 2 ) and for higher cohort-entry BMI (HR 1Á09, 95% CI: 1Á03-1Á16 per 5 kg/m 2 ) and waist circumference (HR = 1Á06, 95% CI: 1Á02-1Á10 per 5 cm). In analyses of the joint effect of young adult and baseline BMI, women who were the heaviest, both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) were at greater risk compared to those with BMI 18Á5 ≤ 25 at both time points (HR = 1Á95, 95% CI: 1Á33-2Á86) but there was no significant association in men. Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood.
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Papers by Michael Alavanja