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IMPH Research in Women's Health and Reproductive Health

Phytoestrogen and Endogenous Estrogen Exposure and Risk of Stroke
Pregnancy Folate Status & Early Childhood Respiratory & Atopic Disease Outcomes
Shanghai Breast Cancer Study (SBCS)
Shanghai Endometrial Cancer Study (SECS)
Understanding the Genetic Risk Underlying Racial Disparities in Uterine Fibroids

Phytoestrogen and Endogenous Estrogen Exposure and Risk of Stroke

Mounting evidence suggests that exposure to exogenous estrogens and estrogenic compounds may increase the risk of stroke in women. Since phytoestrogens are known to possess estrogenic effects and have been marketed as natural and "safe" alternatives to estrogen therapy, significant concerns have been raised as to whether high exposure to phytoestrogens may confer the same risk of stroke. Another intriguing question has also arisen whether endogenous estrogen levels play a role in predicting stroke risk. We propose to address these questions in a prospective cohort of 74,942 adult Chinese women enrolled in the Shanghai Women´s Health Study. Specifically, we will examine the association between dietary intake of soy phytoestrogens and risk of stroke. We will also conduct a nested case-control study among postmenopausal women to investigate the association of ischemic stroke with urinary levels of isoflavonoids and with blood levels of estradiol, estrone, testosterone, and sex hormone- binding globulin. Read more.

Funding Source: NIH/NHLBI
PI: Xianglan Zhang

Pregnancy Folate Status & Early Childhood Respiratory & Atopic Disease Outcomes

The long-term goal of this project is to determine whether maternal folic acid supplementation during pregnancy increases the risk of early childhood asthma and atopy. Supplementation with folic acid, synthetic folate, is recommended during the periconceptional period to prevent neural tube defects (NTD). Studies in different populations have suggested an association between reported folic acid supplementation during pregnancy and increased risk of infant lower respiratory tract infection and early childhood asthma, but data are limited. While adequate intake of folate is essential for prevention of NTDs, it is important to delineate the impact of supplementation on the risk of common respiratory and atopic diseases. Folate plays an important role in DNA methylation, a regulator of gene expression. A causal relationship between folic acid supplementation and respiratory outcomes in children has not been established. However, this relationship does have some biologic plausibility. In a pregnant mouse model, a diet high in methyl donors, including folate, resulted in an augmented allergic phenotype in the offspring, as seen in asthma. Opportunity and Impact. There is no primary prevention strategy for atopic diseases such as asthma. Our objective is to determine whether higher maternal folate intake or the timing of this intake increases the risk of wheezing, asthma, and other atopic diseases in children. This collective work will characterize maternal folate status using objective measures and will assess childhood wheezing, asthma, allergic rhinitis, and atopic dermatitis using validated tools and objective measures. This will be the first investigation in a country with a national fortification program, where individuals may have high intake of folic acid from the diet. Approach. This work will use complementary retrospective and prospective cohorts of mother-child pairs. Specific aim #1 will investigate the population-based incidence of wheezing and asthma during the first 6 years of life, by the timing of folic acid containing prescriptions filled during pregnancy in a retrospective cohort of 80,000 mother-child dyads from the Tennessee Medicaid population. Specific Aim #2 will determine if a) measured maternal plasma folate levels or b) reported folate intake is associated with prospective development of wheezing, asthma, and/or atopy in the first 5 years of life in mother-child dyads enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort. Innovation and Sustainability. This innovative, cost-efficient project will have the advantages of 1) a well-characterized retrospective cohort with a large number of mother-child dyads and determination of folic acid prescriptions filled by month of pregnancy and 2) a prospective cohort that includes the rich, existing infrastructure of the CANDLE cohort with maternal and infant biospecimens, nutritional data, and prospective follow-up using validated tools and objective measures to assess respiratory and atopic outcomes. This study has potential to inform prenatal recommendations and identify modifiable risk factors for asthma and atopy. Read more.

Funding Source: NIH/NHLBI
PI: Kecia Carroll

Shanghai Breast Cancer Study (SBCS)

The Shanghai Breast Cancer Study (SBCS) is a population-based, case-control study funded by NCI since 1996 to investigate lifestyle factors, genetic susceptibility, and other biomarkers associated with breast cancer risk and survival. Included in the study are approximately 3,500 breast cancer cases aged between 25 and 70 years and an equal number of community controls recruited among female residents of Shanghai, China. In addition to in-person interview data, biological samples were collected from study participants. The resources from the study have supported multiple research and training grants and provided opportunities for many graduate students and postdoctoral fellows to conduct research. To date, over 150 research papers have been published from the SBCS addressing a wide range of significant issues related to dietary, lifestyle, environmental, and genetic contributions to breast cancer risk and prognosis.. Read more.

Funding Source: NIH/NCI
PI: Xiao Ou Shu

Shanghai Endometrial Cancer Study (SECS)

The Shanghai Endometrial Cancer Study is a population-based, case-control study of 1,204 endometrial cancer cases and 1,212 controls who were aged between 30 and 69 years and recruited between 1997 and 2003. The study recently recruited an additional 587 endometrial cancer patients. The major objectives of the study are to evaluate the role of and interactions between hormonal, dietary, and other lifestyle factors and genetic susceptibility in endometrial carcinogenesis. In addition to detailed dietary intake and other questionnaire-based information, the study also collected a blood or buccal cell sample and a urine sample from participants. The study has published multiple papers reporting novel findings on dietary risk/protective factors and genetic susceptibility factors. The SECS is one of the largest epidemiological studies of endometrial cancer and is a major contributor to the international Epidemiology of Endometrial Cancer Consortium. Read more.

Funding Source: NIH/NCI
PI: Xiao Ou Shu

Understanding the Genetic Risk Underlying Racial Disparities in Uterine Fibroids

Fibroids affect 77% of women by onset of menopause in the U.S. and account for $9.4 billion in yearly healthcare costs. Until recently, tumor tissue and cell culture studies investigating fibroid growth have been the primary sources for understanding fibroid pathophysiology. In study we propose to identify genetic markers for risk of fibroids through a GWAS of African American and Caucasian participants, leveraging ancestral differences to narrow down genomic regions for targeted follow-up analyses. We will utilize BioVU, an electronic medical records database linked to DNA. Our first Aim is to conduct a GWAS for association between common SNPs and fibroid risk. Secondary admixture mapping analyses will be performed to identify chromosomal regions to prioritize for replication. Finally, in Aim 3 we will replicate SNPs associations in independent samples. This study represents the largest GWAS of fibroids and first among African Americans and leverages emerging technologies and new statistical approaches. Read more.

Funding Source: NIH/NICHD
PI: Digna R. Velez Edwards, PhD