Epigenetic Biomarkers of Breast Cancer Risk: Across the Breast Cancer Prevention Continuum.

Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention).

Exposure to multiple sources of polycyclic aromatic hydrocarbons and breast cancer incidence.

Background: Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction.

Objectives: This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures.

Methods: In a population-based case-control study conducted on Long Island, New York (N=1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake.

Polychlorinated biphenyls and their association with survival following breast cancer.

Background: Polychlorinated biphenyls (PCBs) are hypothesised to influence breast carcinogenesis due to their persistence and potential to induce oestrogenic and anti-oestrogenic effects. Whether PCBs influence survival following breast cancer is unknown.

Methods: A population-based cohort of women diagnosed with first primary invasive or in situ breast cancer in 1996-1997 and with blood-measured PCBs (n=627) collected shortly after diagnosis was followed for vital status through 2011.

Sources of polycyclic aromatic hydrocarbons are associated with gene-specific promoter methylation in women with breast cancer.

Background: Tobacco smoke, diet and indoor/outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear, particularly in breast tissue where methylation may be most relevant. We aimed to evaluate the role of methylation in the association between PAHs and breast cancer.

Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.

Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer.

Polymorphisms in DNA repair genes, recreational physical activity and breast cancer risk.

The mechanisms driving the inverse association between recreational physical activity (RPA) and breast cancer risk are complex. While exercise is associated with increased reactive oxygen species production it may also improve damage repair systems, particularly those that operate on single-strand breaks including base excision repair (BER), nucleotide excision repair (NER) and mismatch repair (MMR). Of these repair pathways, the role of MMR in breast carcinogenesis is least investigated.

Lessons learned in the conduct of a global, large simple trial of treatments indicated for schizophrenia.

Large, "practical" or streamlined trials (LSTs) are used to study the effectiveness and/or safety of medicines in real world settings with minimal study imposed interventions. While LSTs have benefits over traditional randomized clinical trials and observational studies, there are inherent challenges to their conduct. Enrollment and follow-up of a large study sample of patients with mental illness pose a particular difficulty.

Polymorphisms in oxidative stress genes, physical activity, and breast cancer risk.

Purpose: The mechanisms driving the physical activity-breast cancer association are unclear. Exercise both increases reactive oxygen species production, which may transform normal epithelium to a malignant phenotype, and enhances antioxidant capacity, which could protect against subsequent oxidative insult. Given the paradoxical effects of physical activity, the oxidative stress pathway is of interest.

Fat or fit: the joint effects of physical activity, weight gain, and body size on breast cancer risk.

Background: Although physical activity reduces breast cancer risk, issues critical to providing clear public health messages remain to be elucidated. These include the minimum duration and intensity necessary for risk reduction and the optimal time period for occurrence, as well as subgroup effects, particularly with regard to tumor heterogeneity and body size.

Methods: This study investigated the relationship between recreational physical activity (RPA) and breast cancer risk, in addition to characterizing the joint effects of activity level, weight gain, and body size, through use of a population-based sample of 1504 cases (N = 233 in situ, N = 1271 invasive) and 1555 controls (aged 20-98 years) from the Long Island Breast Cancer Study Project, in Long Island, New York.

The epidemiology and clinical correlates of HIV-1 co-receptor tropism in non-subtype B infections from India, Uganda and South Africa.

Background: The introduction of C-C chemokine receptor type-5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co-receptor tropism in different HIV-1 subtypes and geographical locations. This study was undertaken to evaluate HIV-1 co-receptor tropism in the developing world where non-B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions.

Methods: HIV-1-infected patients were recruited into this prospective, cross-sectional, epidemiologic study from HIV clinics in South Africa, Uganda and India.

Influence of prediagnostic recreational physical activity on survival from breast cancer.

Recreational physical activity (RPA) is associated with a reduced risk of developing breast cancer, but there is limited research on whether prediagnostic RPA influences survival after breast cancer diagnosis or not. We evaluated the association between prediagnostic RPA and risk of death in 1508 women with a first breast cancer diagnosis during 1996 and 1997 in the population-based Long Island Breast Cancer Study Project. A 5-year mortality, through the end of 2002, was assessed using the National Death Index (N=196).

Is the large simple trial design used for comparative, post-approval safety research? A review of a clinical trials registry and the published literature.

Post-approval, observational drug safety studies face well known difficulties in controlling for confounding, particularly confounding by indication for drug use. A study design that addresses confounding by indication is the large simple trial (LST). LSTs are characterized by large sample sizes, often in the thousands; broad entry criteria consistent with the approved medication label; randomization based on equipoise, i.

Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow-up: the ziprasidone observational study of cardiac outcomes (ZODIAC).

Purpose: The Ziprasidone Observational study of car DIAC Outcomes (ZODIAC), a large simple trial comparing ziprasidone versus olanzapine in real-world use, showed no difference in risk of sudden death. Upon the request of the US Food and Drug Administration, 205 fatal events were readjudicated applying ICD-10 coding rules for sudden death.

Methods: A readjudication committee coded three domains (witness to death, time of symptom onset to death, and most likely cause of death) for use within algorithms consistent with ICD-10 rules.

Associations between polycyclic aromatic hydrocarbon-related exposures and p53 mutations in breast tumors.

Background: Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology.

Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival.

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR).

PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk.

Background: Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker.

Objective: We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH-DNA adducts and cigarette smoking.

Polycyclic aromatic hydrocarbon-DNA adducts and survival among women with breast cancer.

Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epidemiologic studies have suggested a link between elevated levels of PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA adducts and survival among breast cancer cases has not been previously reported. We conducted a survival analysis among women with newly diagnosed invasive breast cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study Project.

The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC): design and baseline subject characteristics.

Background: Ziprasidone has been used to treat schizophrenia since 2000. It is unknown whether its modest QTc-prolonging effect increases cardiovascular event risk.

Purpose: To describe the study design of the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC).

Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project.

The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk.

Xeroderma pigmentosum complementation group C genotypes/diplotypes play no independent or interaction role with polycyclic aromatic hydrocarbons-DNA adducts for breast cancer risk.

Xeroderma pigmentosum complementation group C (XPC) is an important DNA nuclear excision repair (NER) gene that recognises the damage caused by a variety of bulky DNA adducts. We evaluated the association of two common non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) with breast cancer risk in the Long Island Breast Cancer Study Project (LIBCSP), a population-based case-control study. Genotyping of 1067 cases and 1110 controls was performed by a high throughput assay with fluorescence polarisation.