Lung cancer occurrence in never-smokers: an analysis of 13 cohorts and 22 cancer registry studies.

Background: Better information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions.

Methods And Findings: We pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively.

Novel breast cancer risk alleles and endometrial cancer risk.

Genome-wide association studies have identified several novel risk alleles for breast cancer. We hypothesized that genetic variants that are associated with breast cancer, a hormone-related disease, would also be associated with endometrial cancer, another hormone-related disease. We conducted a case-control study nested within the Nurses' Health Study and the Women's Health Study to investigate the associations between these 7 newly identified risk alleles for breast cancer and endometrial cancer risk using 692 invasive endometrial cancer cases and 1,723 matched controls.

Associations of plasma carotenoids with risk factors and biomarkers related to cardiovascular disease in middle-aged and older women.

Background: Cardiovascular disease (CVD) risk factors may potentially influence plasma concentrations of carotenoids. However, data on the association of plasma carotenoids with CVD related biomarkers are only limited.

Objective: We examined the cross-sectional association of plasma carotenoids with blood lipids, glycated hemoglobin (Hb A(1c)), and C-reactive protein (CRP) in middle-aged and older women initially free of CVD and cancer.

Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy.

Objective: A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk. We investigated whether this allele was associated with elevated Lp(a) and cardiovascular risk in the Women's Health Study, a randomized trial of low-dose aspirin, and whether aspirin reduced cardiovascular risk in minor allele carriers.

Methods And Results: Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants.

Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events.

Background: Although guidelines recommend measuring fasting lipids for initial screening of adults without cardiovascular disease (CVD), recent studies suggest that nonfasting triglycerides may be superior to fasting. Whether fasting status alters associations of nontriglyceride lipids with CVD is unclear.

Methods And Results: In a prospective study of 26 330 healthy women (19 983 fasting; 6347 nonfasting), associations of baseline lipids with incident CVD (754 fasting; 207 nonfasting) were examined over an 11-year follow-up.

Measures of obesity and cardiovascular risk among men and women.

Objectives: This study examined associations between anthropometric measures (body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio [WHtR]) and risk of incident cardiovascular disease (CVD) (including nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death).

Background: Controversy exists regarding the optimal approach to measure adiposity, and the utility of body mass index has been questioned.

Methods: Participants included 16,332 men in the Physicians' Health Study (mean age 61 years in 1991) and 32,700 women in the Women's Health Study (mean age 61 years in 1999).

Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study.

Objective: The renin-angiotensin system and endothelial function have both been associated with hypertension. The aim of the present study was to assess the relationship of six previously characterized gene variants in the renin-angiotensin system and the NOS3 gene with blood pressure progression and incident hypertension.

Methods: We analyzed data from 18 436 Caucasian women who participated in a prospective cohort study and were free of hypertension at baseline.

Migraine, vascular risk, and cardiovascular events in women: prospective cohort study.

Objectives: To evaluate whether the association between migraine with aura and increased risk of cardiovascular disease is modified by vascular risk groups as measured by the Framingham risk score for coronary heart disease.

Design: Prospective cohort study.

Setting: Women's health study, United States.

Interrelationships among the MTHFR 677C>T polymorphism, migraine, and cardiovascular disease.

Background: Interrelationships among the MTHFR 677C>T polymorphism (rs1801133), migraine, and cardiovascular disease (CVD) are plausible but remain controversial.

Methods: Association study among 25,001 white US women, participating in the Women's Health Study, with information on MTHFR 677C>T polymorphism. Migraine and migraine aura status were self-reported.

Association between polymorphisms in the beta2-adrenoceptor gene and migraine in women.

Objective: To investigate the role of three common polymorphisms in the beta2-adrenoceptor gene in migraine.

Background: Migraine has been associated with increased risk of cardiovascular disease and asthma in which beta2-adrenoceptors play an important role; beta-adrenoceptor antagonists are used in migraine prevention. However, the role of variants in the beta2-adrenoceptor gene in migraine is unclear.

Prospective cohort study of type 2 diabetes and the risk of Parkinson's disease.

Objective: To evaluate the association between type 2 diabetes and newly reported Parkinson's disease.

Research Design And Methods: Our study included 21,841 participants in the Physicians' Health Study, a cohort of U.S.

Lipoprotein(a), hormone replacement therapy, and risk of future cardiovascular events.

Objectives: This study assesses whether the relationship of lipoprotein(a) [Lp(a)] with cardiovascular risk may be modified by concurrent hormone replacement therapy (HT).

Background: Prior studies indicate that HT decreases plasma levels of Lp(a), but few have been powered to assess whether it modifies the relationship of Lp(a) with cardiovascular disease (CVD).

Methods: Lipoprotein(a) at baseline was measured among 27,736 initially healthy women, of whom 12,075 indicated active HT use at the time of blood draw at study initiation and 15,661 did not.

IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3).

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts.

Interleukin-18 and the risk of future cardiovascular disease among initially healthy women.

Objective: Elevated levels of interleukin (IL)-18 have been implicated in the development of atherosclerosis in animals. Data in humans are less clear, and data in women are particularly scarce.

Methods And Results: In a prospective nested case-control study of initially healthy women, we measured baseline plasma IL-18 levels in 253 participants who subsequently developed cardiovascular disease (CVD) and in 253 healthy age- and smoking-matched controls.

Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial.

Context: Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.

Objective: To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD.

The joint effects of physical activity and body mass index on coronary heart disease risk in women.

Background: Physical activity and body mass index (calculated as weight in kilograms divided by height in meters squared) independently alter the risk of coronary heart disease (CHD); however, their combined effect on CHD is not established. Our objective was to study the combined association of physical activity and body mass index on CHD.

Methods: Prospective cohort study of 38,987 women free of cardiovascular disease, cancer, and diabetes at baseline in the Women's Health Study, with 10.

Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.

Although elevated levels of C-reactive protein (CRP) independently predict increased risk of development of metabolic syndrome, diabetes, myocardial infarction, and stroke, comprehensive analysis of the influence of genetic variation on CRP is not available. To address this issue, we performed a genome-wide association study among 6345 apparently healthy women in which we evaluated 336,108 SNPs as potential determinants of plasma CRP concentration. Overall, seven loci that associate with plasma CRP at levels achieving genome-wide statistical significance were found (range of p values for lead SNPs within the seven loci: 1.

Parkinson disease and risk of mortality: a prospective comorbidity-matched cohort study.

Objective: To evaluate the association between Parkinson disease (PD) and mortality after adjustment for comorbidities.

Methods: We conducted a matched cohort analysis among 22,071 participants in the Physicians' Health Study. Five hundred sixty incident PD cases were identified by self-report.

MDM2 SNP309 is associated with endometrial cancer risk.

Mouse double-minute 2 homologue (MDM2) is a key negative regulator of p53, a tumor suppressor gene that initiates cell cycle arrest and apoptosis in response to DNA damage and other cellular stresses. A T > G polymorphism found in the promoter region of MDM2 (SNP309) increases MDM2 expression and thereby attenuates p53 activity. We genotyped the MDM2 polymorphism SNP309 in endometrial cancer case-control studies nested within the Nurses' Health Study (454 cases and 1,132 controls) and the Women's Health Study (137 cases and 411 controls).

Type 2 diabetes mellitus and cognitive decline in two large cohorts of community-dwelling older adults.

Objectives: To relate diabetes mellitus (DM) status and duration to late-life cognitive impairment and decline in men and women.

Design: Prospective cohort.

Setting: Community.

Increasing research capacity at the New England School of Acupuncture through faculty and student research training initiatives.

Few complementary and alternative medicine (CAM) institutions require their students to undergo substantive training in research literacy and conduct, and well-developed programs to train CAM institution faculty in research are virtually non-existent. As part of a National Center for Complementary and Alternative Medicine (NCCAM) initiative to increase research capacity at CAM institutions, the New England School of Acupuncture (NESA), in collaboration with the Harvard Medical School (HMS) Osher Institute, was awarded a Developmental Center for Research on Complementary and Alternative Medicine (DCRC) grant. This article discusses a number of initiatives that we designed and implemented to train NESA students, faculty members, and alumni in the foundations of clinical research and to stimulate interest in both participating in research and receiving additional research training.

Height, body mass index, and ovarian cancer: a pooled analysis of 12 cohort studies.

Background: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent.

Methods: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12 prospective cohort studies from North America and Europe. The study population consisted of 531,583 women among whom 2,036 epithelial ovarian cancer cases were identified.

A prospective study of multivitamin supplement use and risk of breast cancer.

The authors evaluated the association between multivitamin supplement use and breast cancer risk in a completed trial. At baseline (1992-1995), 37,920 US women aged > or =45 years and free of cancer provided detailed information on multivitamin supplement use. During an average of 10 years of follow-up, 1,171 cases of invasive breast cancer were documented.

Randomised aspirin assignment and risk of adult-onset asthma in the Women's Health Study.

Background: Randomised data in men show a small but significant reduction in the risk of adult-onset asthma among those given aspirin. The results from an observational study in women suggest that frequent use of aspirin decreases the risk of adult-onset asthma, but randomised data in women are lacking. A study was undertaken to test the effect of 100 mg aspirin or placebo on alternate days on the risk of adult-onset asthma in the Women's Health Study.

Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women.

Background: B vitamins such as folate, vitamin B-6, and vitamin B-12 are coenzymes that are important for DNA integrity and stability. Deficiency in these B vitamins may promote tumor carcinogenesis.

Objective: We prospectively evaluated plasma concentrations of folate, pyridoxal 5-phosphate (PLP; the principal active form of vitamin B-6), and vitamin B-12 in relation to breast cancer risk.