Childhood and Adolescent Pesticide Exposure and Breast Cancer Risk

To date, epidemiological studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Further, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor-subtype specific associations. We examine the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N=50,844 women) to assess this relation by tumor subtype

Antimüllerian hormone in relation to tobacco and marijuana use and sources of indoor heating/cooking

To evaluate exposure to tobacco, marijuana and indoor heating/cooking sources in relation to anti-Müllerian hormone (AMH) levels

Hypoactive Sexual Desire Disorder in Postmenopausal Women: Quality of Life and Health Burden

Abstract Objectives To describe the health-related quality of life (HRQOL) implications of hypoactive sexual desire disorder (HSDD) in a national sample of postmenopausal women ages 30–70. Methods The Nationwide Survey of Female Sexual Health, a random-digit telephone survey of US households, collected information on female sexual function, demographic characteristics, HRQOL, and the presence of specific medical disorders from 1189 naturally or surgically postmenopausal women in stable relationships of ≥3 months duration. HSDD was defined as Results HSDD was associated with significant HRQOL decrements, with the largest SF-12 score differences in mental health (HSDD: 45.4 [standard error 1.9] vs. no HSDD: 51.0 [0.6], P < 0.01), vitality (HSDD: 47.7 [1.3] vs. no HSDD: 52.0 [0.7], P < 0.01), social function (HSDD: 47.3 [1.4] vs. no HSDD: 50.9 [0.7], P < 0.05), and bodily pain (HSDD: 41.4 [2.2] vs. no HSDD: 46.7 [0.9], P < 0.05). EQ-5D index was 0.08 points lower (HSDD: 0.76 [0.03] vs. no HSDD: 0.84 [0.02], P < 0.05) for those with HSDD compared with those without. HSDD was associated with a 0.1-point decrement in naturally menopausal women (HSDD: 0.78 [0.03] vs. no HSDD 0.88 [0.01], P < 0.01). Women with HSDD showed more HRQOL impairment than healthy population norms but were similar to adults with other chronic conditions such as diabetes and back pain. Conclusions Women with HSDD showed substantial impairment in HRQOL. Given a prevalence of 6.6% to 12.5% among US women, HSDD represents an important burden on quality of life

IGF-I and IGFBP-3 Polymorphisms in Relation to Circulating Levels among African American and Caucasian Women

Circulating insulin-like growth factor-one (IGF-I) and IGF binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNPs) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians = 631 ng/ml, 95% confidence interval: 398, 864; African Americans = 897 ng/ml, 95% confidence interval: 656, 1138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than referent diplotypes with the CG genotype, while IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (−202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with 5% or greater differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with 10% or greater differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians, but provides less evidence that IGF-I SNPs affect plasma IGF-I levels

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Early life factors associated with adult onset systemic lupus erythematosus (SLE) in women

Background: Exposure early in life can influence adult disease and immunity, but the role of early life exposures in risk of SLE is not established.Methods: Women in a national cohort (ages 35-74) provided data on perinatal, maternal and sociodemographic factors, longest residence to age 14 and residential farm history of at least 12 months to age 18. Cases (N=124) reported SLE diagnosed age 16 years or older with use of disease modifying anti-rheumatic drugs. Non-cases (N=50,465) did not report lupus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression adjusting for age and race/ethnicity. Results: SLE was associated with low birthweight (data on 84 cases and 36,477 non-cases; 4 weeks early vs. full-term; OR=3.4; 95%CI 1.6, 7.4). Considering longest childhood residence to age 14, SLE was associated with more frequent pesticide use (e.g., at least monthly OR=2.3; 95%CI 1.3, 4.1). SLE was associated with having an early and extended childhood farm residence (i.e., prenatal/maternal farm exposure and longest childhood farm residence; OR=1.8; 95%CI 1.1, 3.0 versus neither). In those with a childhood-only farm residence of 12+ months, agricultural pesticide use was associated with SLE, with the strongest associations for direct personal exposures. Conclusions: The association of SLE with premature birth is consistent with studies in other populations, and with an observed association with low birthweight. The associations of SLE with childhood exposure to residential and agricultural pesticides warrant further study.INTRODUCTIONSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune reactivity to multiple nuclear components and inflammation, resulting in diverse clinical features and multiple organ involvement. The causes of SLE are generally not known. Racial disparities and increased familial risk suggest a genetic predisposition. It is believed that environmental factors may contribute to the development of disease, but knowledge on specific risk factors is mostly limited to occupational exposures[1]. The developmental origins hypothesis has been proposed for many adult-onset, chronic inflammatory diseases, including systemic lupus erythematosus (SLE) [2-6]. Exposures during and after gestation, including nutritional, infectious, chemica

In utero exposure to diethylstilbestrol and blood DNA methylation in women ages 40-59 years from the sister study.

In utero exposure to diethylstilbestrol (DES) has been associated with increased risk of adverse health outcomes such as fertility problems and vaginal as well as breast cancer. Animal studies have linked prenatal DES exposure to lasting DNA methylation changes. We investigated genome-wide DNA methylation and in utero DES exposure in a sample of non-Hispanic white women aged 40-59 years from the Sister Study, a large United States cohort study of women with a family history of breast cancer. Using questionnaire information from women and their mothers, we selected 100 women whose mothers reported taking DES while pregnant and 100 control women whose mothers had not taken DES. DNA methylation in blood was measured at 485,577 CpG sites using the Illumina HumanMethylation450 BeadChip. Associations between CpG methylation and DES exposure status were analyzed using robust linear regression with adjustment for blood cell composition and multiple comparisons. Although four CpGs had p<105, after accounting for multiple comparisons using the false discovery rate (FDR), none reached genome-wide significance. In conclusion, adult women exposed to DES in utero had no evidence of large persistent changes in blood DNA methylation

Antimüllerian hormone in relation to tobacco and marijuana use and sources of indoor heating/cooking

To evaluate exposure to tobacco, marijuana and indoor heating/cooking sources in relation to anti-Müllerian hormone (AMH) levels