Breast cancer and exposure to tobacco smoke during potential windows of susceptibility.

PURPOSE: An association between smoking and breast cancer is unresolved, although a higher risk from exposure during windows of susceptibility has been proposed. The objective of this prospective study was to evaluate the association between tobacco smoke and breast cancer with a focus on timing of exposure, especially during early life. METHODS: Sister study participants (n = 50,884) aged 35-74 were enrolled from 2003 to 2009. Women in the United States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast cancer. Participants completed questionnaires on smoking and environmental tobacco smoke (ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk. RESULTS: During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was associated with breast cancer risk. However, never smoking women exposed to ETS throughout their childhood had a 17% higher risk of breast cancer (95% CI 1.00-1.36) relative to those with no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI 1.01-1.32) and the HR was most elevated for women born in earlier birth cohorts (<1940, HR = 1.44, 95% CI 1.02-2.02; 1940-1949, HR = 1.28, 95% CI 1.01-1.62). CONCLUSION: In utero ETS and ETS exposure during childhood and adolescence were associated with increased risk of breast cancer and associations varied by birth cohort.

The Sister Study Cohort: Baseline Methods and Participant Characteristics.

BACKGROUND: The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. OBJECTIVE: The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. METHODS: A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. RESULTS: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score). Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m2 (70%). Few (5%) reported any cancer prior to enrollment. CONCLUSIONS: The Sister Study is a unique cohort designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive exposure data over the life-course and baseline specimens provide important opportunities for studying breast cancer and other health outcomes in women. Collaborations are welcome. https://doi.org/10.1289/EHP1923.

Risk-benefit profiles of women using tamoxifen for chemoprevention.

BACKGROUND: Tamoxifen has been US Food and Drug Administration-approved for primary prevention of breast cancer since 1998 but has not been widely adopted, in part because of increased risk of serious side effects. Little is known about the risk-benefit profiles of women who use chemoprevention outside of a clinical trial. We examined characteristics associated with initiation and discontinuation of tamoxifen for primary prevention of breast cancer within a large cohort of women with a first-degree family history of breast cancer. METHODS: This research was conducted within The Sister Study, a cohort of 50884 US and Puerto Rican women age 35 to 74 years enrolled from 2003 to 2009. Eligible women were breast cancer-free at enrollment and had a sister who had been diagnosed with breast cancer. Participants reported tamoxifen use, ages started and stopped taking tamoxifen, and total duration of use at enrollment. We identified 788 tamoxifen users and 3131 nonusers matched on age and year of enrollment who had no history of contraindicating factors (stroke, transient ischemic attack, cataract, endometrial or uterine cancer). Characteristics associated with tamoxifen initiation were evaluated with multivariable conditional logistic regression. All statistical tests were two-sided. RESULTS: Based on published risk-benefit indices, 20% of women who used tamoxifen had insufficient evidence that the benefits of tamoxifen outweigh the risk of serious side effects. After 4.5 years, 46% of women had discontinued tamoxifen. CONCLUSIONS: While the majority of women who used tamoxifen for primary prevention of breast cancer were likely to benefit, substantial discontinuation of tamoxifen before five years and use by women at risk of serious side effects may attenuate benefits for breast cancer prevention.

Breast cancer risk after occupational solvent exposure: the influence of timing and setting.

Organic solvents are ubiquitous in occupational settings where they may contribute to risks for carcinogenesis. However, there is limited information on organic solvents as human breast carcinogens. We examined the relationship between occupational exposure to solvents and breast cancer in a prospective study of 47,661 women with an occupational history in the Sister Study cohort. Occupational solvent exposure was categorized using self-reported job-specific solvent use collected at baseline. Multivariable Cox regression analyses were used to assess breast cancer risk, adjusting for established breast cancer risk factors. A total of 1,798 women were diagnosed with breast cancer during follow-up, including 1,255 invasive cases. Overall the risk of invasive breast cancer was not associated with lifetime exposure to solvents [HR, 1.04; 95% confidence interval (CI), 0.88-1.24]. Parous women who worked with solvents before their first full-term birth had an increased risk of estrogen receptor-positive invasive breast cancer compared with women who never worked with solvents (HR, 1.39; 95% CI, 1.03-1.86). A significantly elevated risk for estrogen receptor-positive invasive breast cancer was associated with solvent exposure among clinical laboratory technologists and technicians (HR, 2.00; 95% CI, 1.07-3.73). Occupational exposure to solvents before first birth, a critical period of breast tissue differentiation, may result in increased vulnerability for breast cancer. Our findings suggest a need for future studies in this area to focus on exposure time windows and solvent types in different occupational settings.

Early-life exposures and early-onset uterine leiomyomata in black women in the Sister Study.

BACKGROUND: Uterine leiomyomata (fibroids) are hormonally responsive tumors, but little is known about risk factors. Early-life exposures may influence uterine development and subsequent response to hormones in adulthood. An earlier analysis of non-Hispanic white women who participated in the Sister Study found associations between several early-life factors and early-onset fibroids. OBJECTIVES: We evaluated associations of early-life and childhood exposures with early-onset fibroids among black women and compared the results with those found among white women. METHODS: We analyzed baseline data from 3,534 black women, 35-59 years of age, in the Sister Study (a nationwide cohort of women who had a sister diagnosed with breast cancer) who self-reported information on early-life and childhood exposures. Early-onset fibroids were assessed based on self-report of a physician diagnosis of fibroids by the age of 30 years (n = 561). We estimated risk ratios (RR) and 95% confidence intervals (CI) from log-binomial regression models. RESULTS: Factors most strongly associated with early-onset fibroids were in utero diethylstilbestrol (DES; RR = 2.02; 95% CI: 1.28, 3.18), maternal prepregnancy diabetes or gestational diabetes (RR = 1.54; 95% CI: 0.95, 2.49), and monozygotic multiple birth (RR = 1.94; 95% CI: 1.26, 2.99). We also found positive associations with having been taller or thinner than peers at the age of 10 years and with early-life factors that included being the firstborn child of a teenage mother, maternal hypertensive disorder, preterm birth, and having been fed soy formula. CONCLUSIONS: With the exception of monozygotic multiple birth and maternal hypertensive disorder, early-life risk factors for early-onset fibroids for black women were similar to those found for white women. However, in contrast to whites, childhood height and weight, but not low socioeconomic status indicators, were associated with early-onset fibroids in blacks. The general consistency of early-life findings for black and white women supports a possible role of early-life factors in fibroid development.

Eating patterns and nutritional characteristics associated with sleep duration.

OBJECTIVE: To identify major meal and snack eating patterns, and examine their relationships with sleep duration. DESIGN: The analyses included 27 983 participants in a prospective cohort study of women aged 35 to 74 years in the USA or Puerto Rico. RESULTS: The principal component analysis of eight meal and snack frequency items at different times across the day yielded two major eating patterns: (i) eating during conventional eating hours (defined as times from breakfast to dinner); and (ii) dominance of snacks over meals. Comparing the identified eating patterns among women with varying sleep duration (<5, 5-5·9, 6-6·9, 7-7·9, 8-8·9, 9-9·9 and ≥10 h daily), the tendency for eating during conventional eating hours decreased with decreasing sleep duration: adjusted mean score of -0·54 (95% CI -0·68, -0·41) in women sleeping for <5 h daily v. 0·08 (95% CI 0·06, 0·11) among those with 7-7·9 h of sleep daily. The extent of snack dominance over meals increased in women with shorter sleep. Women with long (≥10 h) sleep duration had eating patterns similar to those with short (<6 h) sleep duration. Lower tendency for eating during conventional eating hours and greater snack dominance over meals were also related to higher intakes of fat and sweets for energy and lower intakes of fruits and vegetables. CONCLUSIONS: Disrupted eating patterns and diet of poor nutritional quality may exacerbate the development of obesity and metabolic diseases in habitual short and very long sleepers.

Association of intrauterine and early-life exposures with diagnosis of uterine leiomyomata by 35 years of age in the Sister Study.

BACKGROUND: Early-life exposures to hormonally active compounds and other factors may affect later response to estrogen or progesterone and hence may influence development of uterine leiomyomata (fibroids). OBJECTIVES: We evaluated associations of in utero and early-life exposures, including soy formula, with self-report of physician-diagnosed fibroids by 35 years of age. METHODS: Our study included 19,972 non-Hispanic white women who were 35-59 years of age when they enrolled in the Sister Study in 20032007. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using log-binomial regression models for fibroid associations with adjustment for participant's age and education, maternal age at participant's birth, birth order, and childhood family income. RESULTS: Greater risk of early fibroid diagnosis was associated with soy formula during infancy (RR = 1.25; 95% CI, 0.971.61), maternal prepregnancy diabetes (RR = 2.05; 95% CI, 1.163.63), low childhood socioeconomic status (RR = 1.28; 95% CI, 1.011.63), and gestational age at birth (RR = 1.64; 95% CI, 1.272.13, for being born at least 1 month early). In utero diethylstilbestrol (DES) exposure was also associated with early fibroid diagnosis (RR = 1.42; 95% CI, 1.131.80), but this association was driven by women reporting probable rather than definite exposure. CONCLUSIONS: There are plausible biological pathways by which these early-life factors could promote fibroid pathogenesis. This is the first epidemiologic study to evaluate such exposures, with the exception of in utero DES, in relation to fibroid risk, and replication of findings in other populations is needed.

Obesity and weight gain in adulthood and telomere length.

Obesity and weight gain in adulthood are associated with an increased risk of several cancers. Telomeres play a critical role in maintaining genomic integrity and may be involved in carcinogenesis. Using data from 647 women ages 35 to 74 years in the United States and Puerto Rico (2003-2004), we examined the association between current and past anthropometric characteristics and telomere length in blood. In a multivariate linear regression model, higher current body mass index (BMI) and hip circumference were inversely associated with telomere length. Higher BMI in the 30s was associated with shorter telomere length among women ages>or=40 years (Ptrend<0.01). Weight gain since the age 30s (Ptrend=0.07) and weight cycling (Ptrend=0.04) were also inversely associated with telomere length. When current BMI and BMI at ages 30 to 39 years were considered together, the most marked decrease in telomere length was found for women who had overweight or obese BMI at both time points (mean telomere repeat copy number to single-copy gene copy number ratio=1.26; 95% confidence interval, 1.21-1.30) compared with women who had normal BMI at both times (mean telomere repeat copy number to single-copy gene copy number ratio=1.33; 95% confidence interval, 1.30-1.36). These findings support the hypothesis that obesity may accelerate aging, and highlight the importance of maintaining a desirable weight in adulthood.

Child delinquency and the prophylaxis of crime in early 20th-century Latin America / La delincuencia infantil y la profilaxis del crimen a principios del siglo XX en América Latina

A fin de ahondar en la visión que predominaba a principios del siglo XX sobre el maltrato infantil, sus efectos sobre el comportamiento de los jóvenes y las estrategias para prevenir la delincuencia juvenil se ofrece una síntesis en inglés de la conferencia " La delincuencia infantil y la profilaxis del crimen" , presentada en 1929 por el pediatra e higienista social colombiano Jorge Bejarano Martínez y se resaltan sus teorías sobre el abuso y la desatención infantil, y la prevención del crimen. Mediante citas del texto original de 88 páginas, esta síntesis presenta los puntos de vista de Bejarano sobre las condiciones sociales que él consideraba cruciales en la etiología de la delincuencia infantil en Colombia (la falta de mecanismos sociales de protección y de oportunidades educacionales para los niños, la pobreza en el hogar, el trabajo infantil, el abandono, y el abuso y la desatención de los niños). Aunque en Colombia aún subsisten problemas de fondo similares, se han logrado avances en la protección de los niños contra el abuso y la desatención para prevenir la delincuencia en etapas posteriores de su vida. Esta conferencia demuestra que Bejarano fue un precursor de estos esfuerzos en América Latina y ofrece elementos sobre los orígenes de las estrategias actuales para reducir la violencia juvenil.