Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort.

Introduction: MicroRNAs (miRNAs) are small, non-coding, single-stranded RNAs between 18-22 nucleotides long that regulate gene expression. Expression of miRNAs is altered in tumor compared to normal tissue; there is some evidence that these changes may be reflected in the serum of cancer cases compared to healthy individuals. This has yet to be examined in a prospective study where samples are collected before diagnosis.

Exacerbation of symptoms in agricultural pesticide applicators with asthma.

Purpose: Exacerbation is a critical event in asthma management. We investigated whether exacerbation of symptoms is associated with farming exposures among agricultural pesticide applicators with asthma.

Methods: Participants were pesticide applicators with active asthma (wheezing and breathing problems in past 12 months) who completed enrollment questionnaires for the Agricultural Health Study (AHS).

Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, case-cohort study of postmenopausal women.

Overweight or obese women are at increased risk of developing and dying from breast cancer. Obesity-driven inflammation may stimulate prostaglandin E2 (PGE2)-mediated aromatase activation and estrogen biosynthesis in breast tissues. We hypothesized that increased production of PGE2 would contribute to elevated breast cancer risk in postmenopausal women.

Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Epigenome-wide association study of breast cancer using prospectively collected sister study samples.

Background: Previous studies have suggested DNA methylation in blood is a potential epigenetic marker of cancer risk, but this has not been evaluated on a genome-wide scale in prospective studies for breast cancer.

Methods: We measured DNA methylation at 27578 CpGs in blood samples from 298 women who developed breast cancer 0 to 5 years after enrollment in the Sister Study cohort and compared them with a random sample of 612 cohort women who remained cancer free. We also genotyped women for nine common polymorphisms associated with breast cancer.

Recreational and household physical activity at different time points and DNA global methylation.

Background: DNA methylation patterns are heritable but can change over time and in response to exposures. Lower global DNA methylation, which may result in increased genomic and chromosomal instability, has been associated with increased cancer risk. Physical activity is a modifiable factor that has been inversely related to the risk of cancer.

Prenatal and infant exposures and age at menarche.

Background: Early menarche is related to increased risk of breast cancer. The number of established factors that contribute to early menarche is limited. We studied prenatal and infant exposures in relation to age at menarche in a nationwide cohort of women who have a family history of breast cancer.

Severe head injury and amyotrophic lateral sclerosis.

Our objective was to examine whether severe head injury, subtypes of head injury, or repeated head injuries are associated with ALS risk based on the Swedish population and health registers. We conducted a case-control study, nested within a cohort of 5,764,522 individuals who were born in Sweden during 1901-1970 and followed between 1991 and 2007. The study included 4004 ALS patients identified from the Swedish Patient Register during follow-up and 20,020 randomly selected controls matched by gender and birth year.

Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study.

Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993-2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence.

Genetic modification of the association of paraquat and Parkinson's disease.

Paraquat is one of the most widely used herbicides worldwide. It produces a Parkinson's disease (PD) model in rodents through redox cycling and oxidative stress (OS) and is associated with PD risk in humans. Glutathione transferases provide cellular protection against OS and could potentially modulate paraquat toxicity.

Menopausal symptoms and the risk of young-onset breast cancer.

Background: Women with menopausal symptoms have been reported to have reduced risk of breast cancer, possibly reflecting differences in endogenous hormone levels. We examined the associations between menopausal symptoms and breast cancer in women under age 50.

Methods: We carried out a sister-controlled case-control study, the Two Sister Study, comparing 1422 women with breast cancer diagnosed before age 50 and their 1669 sisters who were free of breast cancer and had enrolled in the prospective Sister Study cohort.

The Interaction between Pesticide Use and Genetic Variants Involved in Lipid Metabolism on Prostate Cancer Risk.

Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway.

Vitamin D receptor gene haplotypes and polymorphisms and risk of breast cancer: a nested case-control study.

Background: Observational and experimental studies suggest that vitamin D may influence breast cancer etiology. Most known effects of vitamin D are mediated via the vitamin D receptor (VDR). Few polymorphisms in the VDR gene have been well studied in relation to breast cancer risk and results have been inconsistent.

Lifetime organophosphorous insecticide use among private pesticide applicators in the Agricultural Health Study.

Organophosphorous insecticides (OPs) are the most commonly used insecticides in US agriculture, but little information is available regarding specific OP use by individual farmers. We describe OP use for licensed private pesticide applicators from Iowa and North Carolina in the Agricultural Health Study (AHS) using lifetime pesticide use data from 701 randomly selected male participants collected at three time periods. Of 27 OPs studied, 20 were used by >1%.

Association between genetic variants in DNA and histone methylation and telomere length.

Telomere length, a biomarker of aging and age-related diseases, exhibits wide variation between individuals. Common genetic variation may explain some of the individual differences in telomere length. To date, however, only a few genetic variants have been identified in the previous genome-wide association studies.

Fertility drugs and young-onset breast cancer: results from the Two Sister Study.

Background: Fertility drugs stimulate hyperovulation, which may have implications for breast cancer. We examined the association between use of fertility drugs (clomiphene citrate [CC] and follicle-stimulating hormone [FSH]) and subsequent risk of young-onset (<50 years at diagnosis) breast cancer.

Methods: We conducted the Two Sister Study, a sister-matched case-control study, by enrolling 1422 women between September 2008 and December 2010, who were younger than age 50 years at diagnosis with breast cancer and were enrolled within 4 years of diagnosis, and 1669 breast cancer-free control sisters from the Sister Study.

Childhood socioeconomic factors and perinatal characteristics influence development of rheumatoid arthritis in adulthood.

Background: Rheumatoid arthritis (RA) has been associated with lower socioeconomic status (SES), but the reasons for this are not known.

Objective: To examine childhood SES measures, SES trajectory and other perinatal factors in relation to RA.

Methods: The sample included 50 884 women, aged 35-74 (84% non-Hispanic white) enrolled 2004-9 in a US national cohort study.

Using multiple imputation to assign pesticide use for non-responders in the follow-up questionnaire in the Agricultural Health Study.

The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and North Carolina. A follow-up questionnaire administered 5 years later was completed by 36,342 (63%) of the original participants.

Methyl bromide exposure and cancer risk in the Agricultural Health Study.

Purpose: Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects.

Methods: We used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007.

Pesticide exposure and amyotrophic lateral sclerosis.

Our objectives were to summarize literature on the association of amyotrophic lateral sclerosis (ALS) with pesticides as a group and to evaluate associations of ALS with specific pesticides. We conducted a meta-analysis of published studies of ALS and pesticides as a group and investigated the association of ALS with specific pesticides, using data from the Agricultural Health Study (AHS), a cohort including 84,739 private pesticide applicators and spouses. AHS participants provided information on pesticide use at enrollment in 1993-1997.

Pesticide use and fatal injury among farmers in the Agricultural Health Study.

Purpose: To assess whether pesticide use practices were associated with injury mortality among 51,035 male farmers from NC and IA enrolled in the Agricultural Health Study.

Methods: We used Cox proportional hazards models adjusted for age and state to estimate fatal injury risk associated with self-reported use of 49 specific pesticides, personal protective equipment, specific types of farm machinery, and other farm factors collected 1-15 years preceding death. Cause-specific mortality was obtained through linkage to mortality registries.

An updated algorithm for estimation of pesticide exposure intensity in the agricultural health study.

An algorithm developed to estimate pesticide exposure intensity for use in epidemiologic analyses was revised based on data from two exposure monitoring studies. In the first study, we estimated relative exposure intensity based on the results of measurements taken during the application of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (n = 88) and the insecticide chlorpyrifos (n = 17). Modifications to the algorithm weighting factors were based on geometric means (GM) of post-application urine concentrations for applicators grouped by application method and use of chemically-resistant (CR) gloves.

Head injury, α-synuclein Rep1, and Parkinson's disease.

Objective: To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α-synuclein, modifies the association between head injury and Parkinson's disease (PD) risk.

Methods: Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case-Control Historical Interviews (SEARCH), 2 independent case-control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury.