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"Troisi, Rebecca"
صنف حسب:
Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol
This study, involving long-term follow-up of women exposed in utero to diethylstilbestrol (DES) and unexposed controls, showed increased risks of adverse reproductive outcomes, cervical intraepithelial neoplasia of grade 2 or higher, and breast cancer in women exposed to DES.
Soon after the first synthetic estrogen, diethylstilbestrol (DES), was developed in 1938,
1
it was used clinically to prevent complications of pregnancy.
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In the early 1950s, four clinical trials revealed no evidence of efficacy, and DES use declined.
3
–
6
In the late 1960s, an unusual cluster of cases of clear-cell adenocarcinoma of the vagina and cervix in adolescent girls and young women was observed at one hospital.
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The clinicians involved, working with the mothers of these women,
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discovered a strong association between this cancer and in utero exposure to DES.
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Subsequent clinical studies of women exposed to DES in utero showed . . .
Journal Article
Height at diagnosis and birth-weight as risk factors for osteosarcoma
Objectives: Osteosarcoma typically occurs during puberty. Studies of the association between height and/or birthweight and osteosarcoma are conflicting. Therefore, we conducted a large pooled analysis of height and birthweight in osteosarcoma. Methods: Patient data from seven studies of height and three of birth-weight were obtained, resulting in 1,067 cases with height and 434 cases with birth-weight data. We compared cases to the 2000 US National Center for Health Statistics Growth Charts by simulating 1,000 age-and gender-matched controls per case. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between height or birth-weight and risk of osteosarcoma for each study were estimated using logistic regression. All of the case data were combined for an aggregate analysis. Results: Compared to average birth-weight subjects (2,665-4,045 g), individuals with high birth-weight (> 4,046 g) had an increased osteosarcoma risk (OR 1.35, 95% CI 1.01-1.79). Taller than average (51st-89th percentile) and very tall individuals (≥90th percentile) had an increased risk of osteosarcoma (OR 1.35,95% CI 1.18-1.54 and OR 2.60, 95% CI 2.19-3.07, respectively; P trend <0.0001). Conclusions: This is the largest analysis of height at diagnosis and birth-weight in relation to osteosarcoma. It suggests that rapid bone growth during puberty and in utero contributes to OS etiology.
Journal Article
Pubertal timing and breast density in young women: a prospective cohort study
Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk.
From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV.
The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)).
Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.
Journal Article
Childhood environment influences adrenarcheal timing among first-generation Bangladeshi migrant girls to the UK
Adrenarche is a key early life event that marks middle childhood at approximately 7 years of age. Earlier work with British-Bangladeshi migrant women suggested that environmental conditions experienced before adrenarche influence adult reproductive function. We therefore investigated whether Bangladeshi children who migrate to the United Kingdom (UK) reach adrenarche earlier than non-migrants in Bangladesh or the United Kingdom.
Healthy girls, aged 5-16 years, were recruited from schools in Sylhet, Bangladesh and London, England comprising four groups: Sylhetis (n = 165), first-generation migrants to the United Kingdom (n = 42), second-generation girls (n = 162), and British girls of European origin (n = 50). Anthropometric measurements were collected together with questionnaire data for migration and socioeconomic characteristics. Saliva samples were assayed for dehydroepiandrosterone (DHEAS) using enzyme-linked immunosorbent assays. Multiple linear regressions tested for group differences in anthropometric and socioeconomic variables and DHEAS levels. Median ages at adrenarche (DHEAS>400 pg/ml) were estimated using Weibull regression models for parametric survival analysis. Hazard ratios for reaching adrenarche earlier and 95% confidence intervals (CI), both unadjusted and adjusted for anthropometric variables, were estimated from the survival analyses. First-generation migrants had a median age at adrenarche (5.3 years) that was significantly earlier than Sylheti (7.2), second-generation (7.4), and European (7.1) girls. In univariate analyses, first-generation girls reached adrenarche significantly earlier than Sylhetis [HR (CI): 2.8 (1.4-5.5]. In multivariate models, first generation girls still reached adrenarche earlier than Sylhetis after adjusting for height [HR(CI): 1.9 (0.9-4.1)] and weight [HR(CI):1.7 (0.8-3.8)], but these results were attenuated.
We suggest that rapid catch-up growth experienced by first generation girls during early childhood may explain their advanced adrenarche. The environmental conditions leading to an earlier adrenarche, as well as the health implications of this early transition, merit further exploration.
Journal Article
Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study
Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results.
In data from a collaborative follow-up of three U.S. cohorts of DES-exposed sons, we examined the relation of prenatal DES exposure to occurrence of male urogenital abnormalities. Exposure status was determined through review of prenatal records. Mailed questionnaires (1994, 1997, 2001) asked about specified abnormalities of the urogenital tract. Risk ratios (RR) were estimated by Cox regression with constant time at risk and control for year of birth.
Prenatal DES exposure was not associated with varicocele, structural abnormalities of the penis, urethral stenosis, benign prostatic hypertrophy, or inflammation/infection of the prostate, urethra, or epididymus. However, RRs were 1.9 (95% confidence interval 1.13.4) for cryptorchidism, 2.5 (1.54.3) for epididymal cyst, and 2.4 (1.54.4) for testicular inflammation/infection. Stronger associations were observed for DES exposure that began before the 11th week of pregnancy: RRs were 2.9 (1.65.2) for cryptorchidism, 3.5 (2.06.0) for epididymal cyst, and 3.0 (1.75.4) for inflammation/infection of testes.
These results indicate that prenatal exposure to DES increases risk of male urogenital abnormalities and that the association is strongest for exposure that occurs early in gestation. The findings support the hypothesis that endocrine disrupting chemicals may be a cause of the increased prevalence of cryptorchidism that has been seen in recent years.
Journal Article
The role of hormones in the differences in the incidence of breast cancer between Mongolia and the United Kingdom
There are striking differences in breast cancer incidence between Asian and western women. Rates vary substantially within Asia also, with Mongolia's even lower than China's. These profound differences have been speculated to be due in part to diet, mediated by circulating hormone concentrations.
Sex steroid hormone concentrations were measured in women living in Ulaanbaatar, Mongolia and the United Kingdom (U.K.). Diet was obtained by interview and national survey data. Mean hormone differences were compared by country, and systematic variation by number of days since last menstrual period was modeled and adjusted for age and parity; difference in overall area under the curves was assessed.
The diet in Mongolia was higher in meat and dairy than in the U.K. Mean testosterone concentrations were 18.5% lower (p<0.0001) while estradiol concentrations were 19.1% higher (p = 0.02) in Mongolian than British women, adjusted for age and parity. Progesterone was almost 50% higher in Mongolian women (p = 0.04), particularly during the follicular phase and early luteal surge. Hormone concentrations generally were similar in Mongolian women born in Ulaanbaatar compared with those born in rural areas, although there was a decreasing progesterone trend by degree of westernization (rural Mongolia; urban Mongolia; U.K.). Mean hormone differences were similar when restricted to parous women, and with further adjustment for body mass index, height, and smoking status.
These data augment accumulating evidence that circulating estrogens are unlikely to explain reduced breast cancer rates in Asia compared with the west, and suggest casting a wider net with respect to biomarkers. Lower testosterone and higher progesterone in Mongolian women raise the possibility that these hormones may be important to consider. In addition, the almost exclusive dietary reliance of Mongolians on meat and dairy argues against beneficial effects of a low-fat diet on circulating hormones explaining international breast cancer differences.
Journal Article
Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults
AbstractObjectiveTo examine associations between birth defects and cancer from birth into adulthood.DesignPopulation based nested case-control study.SettingNationwide health registries in Denmark, Finland, Norway, and Sweden.Participants62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014.Main outcome measuresRelative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models.ResultsAltogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk.ConclusionsThe increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.
Journal Article
Can physical activity minimize weight gain in women after smoking cessation?
The purpose of this study was to examine prospectively whether exercise can modify weight gain after smoking cessation in women.
Data were analyzed from a 2-year follow-up period (1986-1988) in the Nurses' Health Study, an ongoing cohort of 121,700 US women aged 40 to 75 in 1986.
The average weight gain over 2 years was 3.0 kg in the 1474 women who stopped smoking, and 0.6 kg among the 7832 women who continued smoking. Among women smoking 1 to 24 cigarettes per day, those who quit without changing their levels of exercise gained an average of 2.3 kg more (95% confidence interval [CI] = 1.9, 2.6) than women who continued smoking. Women who quit and increased exercise by between 8 to 16 MET-hours (the work metabolic rate divided by the resting metabolic rate) per week gained 1.8 kg (95% CI = 1.0, 2.5), and the excess weight gain was only 1.3 kg (95% CI = 0.7, 1.9) in women who increased exercise by more than 16 MET-hours per week.
Smoking cessation is associated with a net excess weight gain of about 2.4 kg in middle-aged women. However, this weight gain is minimized if smoking cessation is accompanied by a moderate increase in the level of physical activity.
Journal Article
Similarity of Serum and Plasma Insulin-like Growth Factor Concentrations
Background
Insulin-like growth factors (IGFs) are implicated in many normal physiological processes and pathological states, including cancer. For large consortia projects, it may be necessary to make comparisons among studies with different specimens that were not collected specifically to optimize the measurement of IGFs.
Objective
This study aimed to compare IGFs in matched serum and plasma samples.
Methods
We measured IGF-I, IGF-II, insulin-like growth factor-binding protein (IGFBP)-3, C-peptide, and leptin in serum and ethylenediaminetetraacetic–containing-plasma samples obtained concurrently from 30 healthy women aged 64–80 years in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial using chemiluminescent or colorimetric enzyme-linked immune assays. Coefficients of variation (CVs) and correlations were determined.
Results
Intraassay CVs ranged from 0.4% for IGFBP-3 to 10% for IGF-II. Mean concentrations of all analytes were higher in the serum, but the differences in mean concentrations of the analytes between serum and plasma were all <11%. Concordance correlation coefficients of matched serum/plasma specimens were 0.92, 0.91, 0.82, 0.96, and 0.99 for IGF-I, IGFBP-3, IGF-II, C-peptide, and leptin, respectively.
Conclusion
IGF concentrations measured in serum and plasma are highly correlated but are consistently slightly higher in serum, suggesting that IGF values should be corrected for systematic bias, particularly in consortial efforts when pooling data derived from different specimens.
Journal Article