Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.

Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients.

Estrogen and colorectal cancer incidence and mortality.

Background: The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Women's Health Initiative (WHI) randomized, placebo-controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow-up of 13.

Long-chain ω-3 fatty acid intake and endometrial cancer risk in the Women's Health Initiative.

Background: Inflammation may be important in endometrial cancer development. Long-chain ω-3 (n-3) polyunsaturated fatty acids (LCω-3PUFAs) may reduce inflammation and, therefore, reduce cancer risk. Because body mass is associated with both inflammation and endometrial cancer risk, it may modify the association of fat intake on risk.

The effect of calcium plus vitamin D supplementation on the risk of venous thromboembolism. From the Women's Health Initiative Randomized Controlled Trial.

Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women's Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years.

The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.

A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls).

Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis.

Hysterectomy and urinary incontinence in postmenopausal women.

Introduction And Hypothesis: To evaluate an association between hysterectomy and urinary incontinence (UI) in postmenopausal women.

Methods: Women (aged 50-79) with uteri (N = 53,569) and without uteri (N = 38,524) who enrolled in the Women's Health Initiative (WHI) Observational Study between 1993 and 1996 were included in this secondary analysis. Baseline (BL) and 3-year demographic, health/physical forms and personal habit questionnaires were used.

Genome-wide interaction study of smoking and bladder cancer risk.

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure.

Validity of diabetes self-reports in the Women's Health Initiative.

Objective: This study aims to determine the positive and negative predictive values of self-reported diabetes during the Women's Health Initiative (WHI) clinical trials.

Methods: All WHI trial participants from four field centers who self-reported diabetes at baseline or during follow-up, as well as a random sample of women who did not self-report diabetes, were identified. Women were surveyed regarding diagnosis and treatment.

Genome-wide association study identifies multiple loci associated with bladder cancer risk.

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls.

Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women's Health Initiative.

Background: Clinical outcomes of the Women's Health Initiative (WHI) calcium plus vitamin D supplementation trial have been reported during 7.0 years of active intervention. We now report outcomes 4.

Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women's Health Initiative observational study.

An increased risk of breast cancer has been reported in patients with non-melanomatous skin cancer (NMSC), but this association has not been studied in a large, multi-geographic population. We utilized data from the Women's Health Initiative observational study to assess whether history of NMSC is associated with breast cancer risk. This analysis included 70,246 postmenopausal White and Hispanic women aged 50-79, in which 4,247 breast cancer cases were identified over a mean (SD) of 11.

Walking speed, physical activity, and breast cancer in postmenopausal women.

Higher self-reported physical activity is associated with lower breast cancer incidence and mortality. Objectively measured timed walking speed, predictive of longevity in older adults, has been associated with ambulatory physical activity in small studies but definitive assessment of the association is lacking. Participants were a subset of 14 719 postmenopausal women in the Women's Health Initiative study who, at entry, had 10 m, timed walking speed determined.

Prospective analysis of association between use of statins or other lipid-lowering agents and colorectal cancer risk.

Purpose: To determine whether 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of colorectal cancer.

Methods: The population included 159,219 postmenopausal women enrolled in the Women's Health Initiative in which 2000 pathologically confirmed cases of colorectal cancer were identified during an average of 10.7 (S.

Racial differences in colorectal cancer incidence and mortality in the Women's Health Initiative.

Background: Colorectal cancer (CRC) incidence and mortality rates are higher in African-Americans as compared with other racial/ethnic groups. The women's health initiative (WHI) study sample was used to determine whether differences in CRC risk factors explain racial/ethnic differences in incidence and mortality.

Methods: The WHI is a longitudinal study of postmenopausal women recruited from 40 centers.

Oophorectomy vs ovarian conservation with hysterectomy: cardiovascular disease, hip fracture, and cancer in the Women's Health Initiative Observational Study.

Background: Elective bilateral salpingo-oophorectomy (BSO) is routinely performed with hysterectomy for benign conditions despite conflicting data on long-term outcomes.

Methods: This is a prospective cohort of 25 448 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study who had a history of hysterectomy and BSO (n = 14 254 [56.0%]) or hysterectomy with ovarian conservation (n = 11 194 [44.

Obesity in relation to endometrial cancer risk and disease characteristics in the Women's Health Initiative.

Objective: Obesity increases endometrial cancer risk, yet its impact on disease stage and grade is unclear. We prospectively examined the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on incidence, stage, and grade of endometrial cancer.

Methods: We studied 86937 postmenopausal women enrolled in the Women's Health Initiative.

Lung cancer among postmenopausal women treated with estrogen alone in the women's health initiative randomized trial.

Background: In the Women's Health Initiative (WHI) randomized controlled trial, use of estrogen plus progestin increased lung cancer mortality. We conducted post hoc analyses in the WHI trial evaluating estrogen alone to determine whether use of conjugated equine estrogen without progestin had a similar adverse influence on lung cancer.

Methods: The WHI study is a randomized, double-blind, placebo-controlled trial conducted in 40 centers in the United States.

Oral bisphosphonate use and breast cancer incidence in postmenopausal women.

Purpose: Emerging clinical evidence suggests intravenous bisphosphonates may inhibit breast cancer while oral bisphosphonates have received limited evaluation regarding breast cancer influence.

Patients And Methods: The association between oral bisphosphonate use and invasive breast cancer was examined in postmenopausal women enrolled onto the Women's Health Initiative (WHI). We compared a published hip fracture prediction model, which did not incorporate bone mineral density (BMD), with total hip BMD in 10,418 WHI participants who had both determinations.

Calcium/vitamin D supplementation and coronary artery calcification in the Women's Health Initiative.

Objective: Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo.

Psychosocial effects of physical and verbal abuse in postmenopausal women.

Purpose: The purpose of this study was to examine the psychological effects of physical and verbal abuse in a cohort of older women.

Methods: This observational cohort study was conducted at 40 clinical sites nationwide that are part of the Women's Health Initiative (WHI) Observational Study. We surveyed 93,676 women aged 50 to 79 years using the mental health subscales and the combined mental component summary (MCS) score of the RAND Medical Outcomes Study 36-item instrument.

Evaluation of the American Heart Association cardiovascular disease prevention guideline for women.

Background: The 2007 update to the American Heart Association (AHA) guidelines for cardiovascular disease prevention in women recommend a simplified approach to risk stratification. We assigned Women's Health Initiative participants to risk categories as described in the guideline and evaluated clinical event rates within and between strata.

Methods And Results: The Women's Health Initiative enrolled 161 808 women ages 50 to 79 years and followed them prospectively for 7.

Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial.

Background: In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period.

Low-fat, increased fruit, vegetable, and grain dietary pattern, fractures, and bone mineral density: the Women's Health Initiative Dietary Modification Trial.

Background: The effects of dietary changes on osteoporosis, low bone density, and frequent falls are unestablished.

Objective: We assessed the effect of the Women's Health Initiative Dietary Modification low-fat and increased fruit, vegetable, and grain intervention on incident hip, total, and site-specific fractures and self-reported falls, and, in a subset, on bone mineral density (BMD).

Design: Postmenopausal women (n = 48,835) aged 50-79 y (18.