Pathways From Socioeconomic Factors to Major Cardiovascular Events Among Postmenopausal Veteran and Nonveteran Women: Findings From the Women's Health Initiative.

Background: Cardiovascular disease (CVD) remains a leading cause of death for women in the United States, with veterans being at potentially higher risk than their nonveteran counterparts due to accelerated aging and distinct biopsychosocial mechanisms. We examined pathways between selected indicators of socioeconomic status (SES) such as education, occupation, household income, and neighborhood SES and major CVD events through lifestyle and health characteristics among veteran and nonveteran postmenopausal women.

Methods And Results: A total of 121 286 study-eligible WHI (Women's Health Initiative) participants (3091 veterans and 118 195 nonveterans) were prospectively followed for an average of 17 years, during which 16 108 major CVD events were documented.

DNA-methylation age and accelerated epigenetic aging in blood as a tumor marker for predicting breast cancer susceptibility.

Background: DNA methylation (DNAm)-based marker of aging, referred to as 'epigenetic age' or 'DNAm age' is a highly accurate multi-tissue biomarker for aging, associated with age-related disease risk, including cancer. Breast cancer (BC), an age-associated disease, is associated with older DNAm age and epigenetic age acceleration (age accel) at tissue levels. But this raises a question on the predictability of DNAm age/age accel in BC development, emphasizing the importance of studying DNAm age in pre-diagnostic peripheral blood (PB) in BC etiology and prevention.

Diabetes risk reduction diet and risk of liver cancer and chronic liver disease mortality: A prospective cohort study.

Background: We aimed to prospectively evaluate the association between a diabetes risk reduction diet (DRRD) score and the risk of liver cancer development and chronic liver disease-specific mortality.

Methods: We included 98,786 postmenopausal women from the Women's Health Initiative-Observational Study and the usual diet arm of the Diet Modification trial. The DRRD score was derived from eight factors: high intakes of dietary fiber, coffee, nuts, polyunsaturated fatty acids, low intakes of red and processed meat, foods with high glycemic index, sugar-sweetened beverages (SSBs), and trans fat based on a validated Food-Frequency Questionnaire administered at baseline (1993-1998).

Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.

JCO We report long-term colorectal cancer findings from the Women's Health Initiative trial where 16,608 postmenopausal women with a uterus were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo.

Novel DNA methylation-based epigenetic signatures in colorectal cancer from peripheral blood leukocytes.

Colorectal cancer (CRC) is a multifactorial disease characterized by accumulation of multiple genetic and epigenetic alterations, transforming colonic epithelial cells into adenocarcinomas. Alteration of DNA methylation (DNAm) is a promising biomarker for predicting cancer risk and prognosis, but its role in CRC tumorigenesis is inconclusive. Notably, few DNAm studies have used pre-diagnostic peripheral blood (PB) DNA, causing difficulty in postulating the underlying biologic mechanism of CRC initiation.

Changes in physical function in older women with endometrial cancer with or without adjuvant therapy.

Objective: To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women's Health Initiative Life and Longevity after Cancer cohort.

Materials And Methods: This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests.

Bilateral Oophorectomy and Colorectal Cancer Incidence and Mortality in the Women's Health Initiative.

Background: The few cohort studies examining oophorectomy and colorectal cancer risk provide mixed results. Therefore, we examined this issue in Women's Health Initiative Observational Study participants.

Methods: A total of 71,312 postmenopausal women were followed for 22.

Menopausal hormone therapy and change in physical activity in the Women's Health Initiative hormone therapy clinical trials.

Objective: The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal women.

Biomarkers of glucose homeostasis as mediators of the relationship of body mass index and waist circumference with COVID-19 outcomes among postmenopausal women: The Women's Health Initiative.

Background & Aims: Systematic reviews, meta-analyses and Mendelian randomization studies suggest that cardiometabolic diseases may be associated with COVID-19 risk and prognosis, with evidence implicating insulin resistance (IR) as a common biological mechanism. As driving factors for IR, we examined body mass index (BMI) and waist circumference (WC) among postmenopausal women in association with COVID-19 outcomes (positivity and hospitalization), and the role of glucose homeostasis as a mediator of this relationship.

Methods: Associations of BMI and WC at baseline (1993-1998) with COVID-19 outcomes collected at Survey 1 (June-December, 2020) and/or Survey 2 (September-December, 2021) were evaluated among 42,770 Women's Health Initiative (WHI) participants (baseline age: 59.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers. We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers. A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004).

Birth weight, adult body size, and risk of colorectal cancer.

Background: Evidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined.

Method: Cox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women's Health Initiative.

Estimating heritability explained by local ancestry and evaluating stratification bias in admixture mapping from summary statistics.

The heritability explained by local ancestry markers in an admixed population provides crucial insight into the genetic architecture of a complex disease or trait. Estimation of can be susceptible to biases due to population structure in ancestral populations. Here, we present a novel approach, Heritability estimation from Admixture Mapping Summary STAtistics (HAMSTA), which uses summary statistics from admixture mapping to infer heritability explained by local ancestry while adjusting for biases due to ancestral stratification.

DNA methylation patterns associated with breast cancer prognosis that are specific to tumor subtype and menopausal status.

Tumor subtype and menopausal status are strong predictors of breast cancer (BC) prognosis. We aimed to find and validate subtype- or menopausal-status-specific changes in tumor DNA methylation (DNAm) associated with all-cause mortality or BC progression. Associations between site-specific tumor DNAm and BC prognosis were estimated among The Cancer Genome Atlas participants ( = 692) with Illumina Infinium HumanMethylation450 BeadChip array data.

DNA methylation in peripheral blood leukocytes for the association with glucose metabolism and invasive breast cancer.

Background: Insulin resistance (IR) is a well-established factor for breast cancer (BC) risk in postmenopausal women, but the interrelated molecular pathways on the methylome are not explicitly described. We conducted a population-level epigenome-wide association (EWA) study for DNA methylation (DNAm) probes that are associated with IR and prospectively correlated with BC development, both overall and in BC subtypes among postmenopausal women.

Methods: We used data from Women's Health Initiative (WHI) ancillary studies for our EWA analyses and evaluated the associations of site-specific DNAm across the genome with IR phenotypes by multiple regressions adjusting for age and leukocyte heterogeneities.

Genetic variants of glucose metabolism and exposure to smoking in African American breast cancer.

Insulin resistance (IR) is a well-established risk factor for breast cancer (BC) development in African American (AA) postmenopausal women. While obesity and IR are more prevalent in AA than in white women, they are under-represented in genome-wide studies for systemic regulation of IR. By examining 780 genome-wide IR single-nucleotide polymorphisms (SNPs) available in our data, we tested 4689 AA women in a Random Survival Forest framework.

Genetic pleiotropy underpinning adiposity and inflammation in self-identified Hispanic/Latino populations.

Background: Concurrent variation in adiposity and inflammation suggests potential shared functional pathways and pleiotropic disease underpinning. Yet, exploration of pleiotropy in the context of adiposity-inflammation has been scarce, and none has included self-identified Hispanic/Latino populations. Given the high level of ancestral diversity in Hispanic American population, genetic studies may reveal variants that are infrequent/monomorphic in more homogeneous populations.

Synergistic Effects of Genetic Variants of Glucose Homeostasis and Lifelong Exposures to Cigarette Smoking, Female Hormones, and Dietary Fat Intake on Primary Colorectal Cancer Development in African and Hispanic/Latino American Women.

Background: Disparities in cancer genomic science exist among racial/ethnic minorities. Particularly, African American (AA) and Hispanic/Latino American (HA) women, the 2 largest minorities, are underrepresented in genetic/genome-wide studies for cancers and their risk factors. We conducted on AA and HA postmenopausal women a genomic study for insulin resistance (IR), the main biologic mechanism underlying colorectal cancer (CRC) carcinogenesis owing to obesity.

Genetic Signatures of Glucose Homeostasis: Synergistic Interplay With Long-Term Exposure to Cigarette Smoking in Development of Primary Colorectal Cancer Among African American Women.

Introduction: Insulin resistance (IR)/glucose intolerance is a critical biologic mechanism for the development of colorectal cancer (CRC) in postmenopausal women. Whereas IR and excessive adiposity are more prevalent in African American (AA) women than in White women, AA women are underrepresented in genome-wide studies for systemic regulation of IR and the association with CRC risk.

Methods: With 780 genome-wide IR single-nucleotide polymorphisms (SNPs) among 4,692 AA women, we tested for a causal inference between genetically elevated IR and CRC risk.

Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis.

As key inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL6) play an important role in the pathogenesis of non-inflammatory diseases, including specific cancers, such as breast cancer (BC). Previous genome-wide association studies (GWASs) have neither explained the large proportion of genetic heritability nor provided comprehensive understanding of the underlying regulatory mechanisms. We adopted an integrative genomic network approach by incorporating our previous GWAS data for CRP and IL6 with multi-omics datasets, such as whole-blood expression quantitative loci, molecular biologic pathways, and gene regulatory networks to capture the full range of genetic functionalities associated with CRP/IL6 and tissue-specific key drivers (KDs) in gene subnetworks.

Interactions Between Adiponectin-Pathway Polymorphisms and Obesity on Postmenopausal Breast Cancer Risk Among African American Women: The WHI SHARe Study.

Background: A decreased level of serum adiponectin is associated with obesity and an increased risk of breast cancer among postmenopausal women. Yet, the interplay between genetic variants associated with adiponectin phenotype, obesity, and breast cancer risk is unclear in African American (AA) women.

Methods: We examined 32 single-nucleotide polymorphisms (SNPs) previously identified in genome-wide association and replication studies of serum adiponectin levels using data from 7,991 AA postmenopausal women in the Women's Health Initiative SNP Health Association Resource.