Menarche, menopause, years of menstruation, and the incidence of osteoporosis: the influence of prenatal exposure to diethylstilbestrol.

Context: Estrogen is critical for bone formation and growth in women. Estrogen exposures occur throughout life, including prenatally, and change with reproductive events, such as menarche and menopause.

Objective: The objective of this study was to investigate the association between age at menarche, age at menopause, and years of menstruation with incidence of osteoporosis and assess the impact of prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, on such associations.

Prenatal DES exposure in relation to breast size.

Purpose: Prenatal DES exposure has been associated with increased risk of breast cancer, but the mechanisms are unknown. Larger bra cup size has also been associated with increased breast cancer risk, although not consistently. We investigated the relation of prenatal DES exposure to mammary gland mass, as estimated by bra cup size.

Medical conditions among adult offspring prenatally exposed to diethylstilbestrol.

Background: Diethylstilbestrol (DES), a synthetic estrogen that was used in pregnancy, is a prototype endocrine-disrupting chemical. Although prenatal exposure to DES is known to increase risks of vaginal/cervical adenocarcinoma and adverse reproductive outcomes in women, and urogenital anomalies in men, data on nonreproductive medical conditions are lacking.

Methods: We estimated hazard ratios and their associated 95% confidence intervals for the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis, and related conditions among 5590 female and 2657 male offspring followed from 1994 through 2006, adjusted for birth year, cohort, sex, body mass index, smoking status, alcohol use, education, and number of general physical examinations in the past 5 years.

Telomere length and genetic variation in telomere maintenance genes in relation to ovarian cancer risk.

Background: Telomeres protect chromosomal ends, shorten with cellular division, and signal cellular senescence, but unchecked telomere attrition can lead to telomere dysfunction, upregulation of telomerase, and carcinogenesis. Shorter telomeres in peripheral blood leukocytes (PBL) have been associated with elevated cancer risk. Furthermore, genetic variants in and around the TERT gene have been implicated in carcinogenesis.

Mammography screening behaviors of women exposed prenatally to diethylstilbestrol.

Background: In utero diethylstilbestrol (DES) exposure is a risk factor for rare development of vaginal and cervical cancer and may potentially be a risk factor for breast cancer. Mammography use in this population is relatively unknown; therefore, this study aims to determine if in utero DES exposure is associated with the frequency of mammography screening examinations while considering demographic and clinical factors.

Methods: Using combined DES cohort questionnaire data, self-reported mammography screening over the past 5 years (2001-2006) was analyzed in women aged ≥45 years.

Adverse health outcomes in women exposed in utero to diethylstilbestrol.

Background: Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood.

Methods: We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls.

Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium.

A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci.

Reproductive factors and histologic subtype in relation to mortality after a breast cancer diagnosis.

Evidence suggests that certain reproductive factors are more strongly associated with the incidence of lobular than of ductal breast cancer. The mechanisms influencing breast cancer incidence histology may also affect survival. Women with invasive breast cancer (N = 22,302) diagnosed during 1986-2005 were enrolled in a series of population-based studies in three US states.

Adolescent weight status and receptivity to food TV advertisements.

Objective: This study examined the relationship between adolescent weight status and food advertisement receptivity.

Design: Survey-based evaluation with data collected at baseline (initial and at 2 months), and at follow-up (11 months).

Setting: New Hampshire and Vermont.

Late age at first full term birth is strongly associated with lobular breast cancer.

Background: Late age at first full-term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades.

Methods: The purpose of this population-based case-control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer.

Assessing ovarian cancer risk when considering elective oophorectomy at the time of hysterectomy.

Objective: To develop a risk-factor score that may provide additional guidance to women and their physicians regarding elective bilateral salpingo-oophorectomy at the time of hysterectomy.

Methods: From a case-control study conducted from 1992 to 2008 in women residing in eastern Massachusetts or New Hampshire, we selected 1,098 women with invasive ovarian cancer (case group) and 1,363 for the control group who were older than 40 years and had neither hysterectomy nor a personal or family history of breast or ovarian cancer. Using logistic regression, we identified key risk factors and built a risk score.

Bilateral oophorectomy in relation to risk of postmenopausal breast cancer: confounding by nonmalignant indications for surgery?

Bilateral oophorectomy is often performed during hysterectomy for benign conditions and can reduce breast cancer risk by 20%-50% when performed at younger ages. Accuracy of estimating the decrease in breast cancer risk associated with bilateral oophorectomy could be affected by common conditions that lead to surgery, such as uterine fibroids or endometriosis. The authors examined the potential for confounding by nonmalignant indications for surgery on breast cancer risk estimates in a population-based case-control study of invasive breast cancer newly diagnosed in 1992-1995.

Replication and functional genomic analyses of the breast cancer susceptibility locus at 6q25.1 generalize its importance in women of chinese, Japanese, and European ancestry.

We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.

Post-diagnosis dietary factors and survival after invasive breast cancer.

Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20-79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire.

Preterm birth, fetal growth, and age at menarche among women exposed prenatally to diethylstilbestrol (DES).

Diethylstilbestrol (DES), a synthetic estrogen used in pregnancy during the 1950s and 1960s, provides a model for potential health effects of endocrine disrupting compounds in the environment. We evaluated prenatal exposure to DES, based on medical record review, in relation to gestational length, fetal growth, and age at menarche in 4429 exposed and 1427 unexposed daughters. DES exposure was associated with an increase in preterm birth (odds ratio (OR)=2.

Perceived intrinsic barriers to physical activity among rural mothers.

Background: The purpose of this study was to identify and determine the influence of perceived intrinsic barriers to physical activity among mothers living in rural areas.

Methods: Mothers were identified through a study of child-parent dyads in the predominantly rural states of New Hampshire and Vermont. Using a telephone interview, we asked mothers (n = 1691) about their level of physical activity and assessed eight potential barriers to physical activity.

MTHFR polymorphisms in relation to ovarian cancer risk.

Objective: Folate has been hypothesized to influence carcinogenesis due to its dual role in DNA methylation, which regulates gene expression, and synthesis of purine and thymidylate, which is vital for DNA repair. Thus, we examined ovarian cancer risk in relation to two functional polymorphisms (C677T and A1298C) in the MTHFR gene.

Methods: We genotyped the C677T (rs1801133) and A1298C (rs1801131) MTHFR polymorphisms in 1642 cases and 2068 controls from three studies, the New England Case Control Study (NEC), Nurses' Health Study (NHS), and Mayo Clinic Ovarian Cancer Case Control Study (MAY).

Social networks and survival after breast cancer diagnosis.

Introduction: Evidence has been inconsistent regarding the impact of social networks on survival after breast cancer diagnosis. We prospectively examined the relation between components of social integration and survival in a large cohort of breast cancer survivors.

Methods: Women (N=4,589) diagnosed with invasive breast cancer were recruited from a population-based, multi-center, case-control study.

Autoimmune disease incidence among women prenatally exposed to diethylstilbestrol.

Objective: Animal studies have suggested that prenatal diethylstilbestrol (DES) exposure may alter immune system development and function including antigen self-recognition. A cohort study was conducted to investigate whether prenatal DES exposure might influence the incidence of at least some specific autoimmune diseases in women.

Methods: A group of women who were and were not prenatally exposed to DES have been followed for more than 25 years for numerous health outcomes including autoimmune disease.

Sleep duration and obesity in a population-based study.

Background: Previous studies have demonstrated an association between sleep duration and obesity, but few population-based studies have examined the association. We examined the relationship between recent and usual lifetime sleep duration with the odds of obesity in 5549 women that participated in a population-based telephone survey.

Methods: The structured telephone interview included questions on usual sleep duration in adult life and the recent past, as well as height and weight and other demographic and lifestyle characteristics.

Smart density: A more accurate method of measuring rural residential density for health-related research.

Background: Studies involving the built environment have typically relied on US Census data to measure residential density. However, census geographic units are often unsuited to health-related research, especially in rural areas where development is clustered and discontinuous.

Objective: We evaluated the accuracy of both standard census methods and alternative GIS-based methods to measure rural density.

Association of COMT haplotypes and breast cancer risk in caucasian women.

Catechol-O-methyl transferase (COMT) is an important estrogen-metabolizing enzyme, and common genetic variants in this gene could affect breast cancer risk. We conducted a large population-based case control study in Massachusetts, New Hampshire, and Wisconsin to examine six strategically selected COMT haplotype-tagging (ht) single nucleotide polymorphism (SNPs), including the val158met polymorphism (rs4680), in relation to breast cancer risk. Analyses were based on 1,655 Caucasian women with invasive breast cancer and 1,470 Caucasian controls.

Interaction between use of non-steroidal anti-inflammatory drugs and selected genetic polymorphisms in ovarian cancer risk.

Inflammation and non-steroidal anti-inflammatory agents (NSAIDs) may play important role in ovarian cancer. However, epidemiologic data are inconsistent, possibly reflecting inter-individual genetic differences affecting the metabolism of NSAIDs. We examined whether common polymorphisms affecting the metabolism of NSAIDs modify the association between NSAIDs and ovarian cancer risk.

A polymorphism in the GALNT2 gene and ovarian cancer risk in four population based case-control studies.

Recent epidemiologic evidence supports a role for MUC1 in ovarian carcinogenesis; therefore, we hypothesized that common genetic variation in the genes responsible for glycosylation of MUC1 may influence ovarian cancer risk. In a genome-wide association study of ovarian cancer, we observed an association between a non-synonymous SNP (rs2271077) in the UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosainyltransferase 2 (GALNT2) gene and ovarian cancer risk (p=0.005).