Deep targeted sequencing of 12 breast cancer susceptibility regions in 4611 women across four different ethnicities.

Background: Although genome-wide association studies (GWASs) have identified thousands of disease susceptibility regions, the underlying causal mechanism in these regions is not fully known. It is likely that the GWAS signal originates from one or many as yet unidentified causal variants.

Methods: Using next-generation sequencing, we characterized 12 breast cancer susceptibility regions identified by GWASs in 2288 breast cancer cases and 2323 controls across four populations of African American, European, Japanese, and Hispanic ancestry.

Benzene Uptake and Glutathione S-transferase T1 Status as Determinants of S-Phenylmercapturic Acid in Cigarette Smokers in the Multiethnic Cohort.

Research from the Multiethnic Cohort (MEC) demonstrated that, for the same quantity of cigarette smoking, African Americans and Native Hawaiians have a higher lung cancer risk than Whites, while Latinos and Japanese Americans are less susceptible. We collected urine samples from 2,239 cigarette smokers from five different ethnic groups in the MEC and analyzed each sample for S-phenylmercapturic acid (SPMA), a specific biomarker of benzene uptake. African Americans had significantly higher (geometric mean [SE] 3.

Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups.

Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation and flavin monooxygenase 3-catalyzed N-oxidation in five ethnic/racial groups and the role of UGT2B10 genotype on the metabolic patterns observed. Nicotine and its metabolites were quantified in urine from African American (AA, n = 364), Native Hawaiian (NH, n = 311), White (n = 437), Latino (LA, n = 453) and Japanese American (JA, n = 674) smokers.

Depsipeptides from a Guamanian Marine Cyanobacterium, Lyngbya bouillonii, with Selective Inhibition of Serine Proteases.

Bouillomides A (1) and B (2) are two depsipeptide analogues of dolastatin 13. Isolated from a Guamanian sample of Lyngbya bouillonii, the planar structures were elucidated on the basis of HR-ESI-MS and NMR data, while the absolute configurations were determined by employing functional group conversions, modified Marfey's analysis, and detailed analyses of ROESY correlations. Compounds 1 and 2 selectively inhibited serine proteases elastase (IC(50) = 1.

Prostate cancer susceptibility variants confer increased risk of disease progression.

Background: Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNP) associated with the risk of prostate cancer. Our objective was to determine whether these SNPs affect the progression of prostate cancer.

Methods: We genotyped 26 SNPs previously associated with prostate cancer risk among 788 aggressive prostate cancer patients who were treated by radical prostatectomy or radiation therapy.

Using the Social-Ecological Model as a research and intervention framework to understand and mitigate obesogenic factors in Samoan populations.

Objective: The purpose of this study is to identify the relevant contributions and interactions of political, socioeconomic, cultural, and biological factors toward the increasing rates of obesity in Samoans. The constructs of the Social-Ecological Model of Health, which posit that there are multiple levels of influence on individual health behaviors, are used as a conceptual framework to synthesize the current research investigating obesity and chronic diseases in Samoan populations.

Design: Twenty-five studies, representing over 20 years of empirical research with Samoans, were assessed and synthesized.

Physical activity and change in mammographic density: the Study of Women's Health Across the Nation.

One potential mechanism by which physical activity may protect against breast cancer is by decreasing mammographic density. Percent mammographic density, the proportion of dense breast tissue area to total breast area, declines with age and is a strong risk factor for breast cancer. The authors hypothesized that women who were more physically active would have a greater decline in percent mammographic density with age, compared with less physically active women.

Mammographic density change with 1 year of aerobic exercise among postmenopausal women: a randomized controlled trial.

Background: The Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial examined the influence of aerobic exercise on biological factors that are associated with breast cancer risk. Mammographic density, a secondary outcome, is reported here.

Methods: The ALPHA Trial was a parallel group randomized controlled trial conducted between May 2003 and July 2007.

Coenzyme Q10 in human blood: native levels and determinants of oxidation during processing and storage.

Coenzyme Q10 (Q10) is present in the circulation mainly in its reduced form (ubiquinol-10; UL10), but oxidizes quickly ex vivo to ubiquinone-10 (UN10). Therefore, native UL10:UN10 ratios, used as markers of redox status and disease risk, are difficult to measure. We established an RP-(U)HPLC method with coulometric detection to measure natively circulating UL10 and UN10 concentrations by adding a ubiquinol/ubiquinone mixture as an internal standard immediately after plasma preparation.

Prostatitis, sexually transmitted diseases, and prostate cancer: the California Men's Health Study.

Background: Prostatitis and sexually transmitted diseases (STDs) have been positively associated with prostate cancer in previous case-control studies. However, results from recent prospective studies have been inconclusive. METHODOGY/PRINCIPAL FINDINGS: We investigated the association between prostatitis, STDs, and prostate cancer among African American, Asian American, Latino, and White participants of the California Men's Health Study.

New methods to explore marine resources for Alzheimer's therapeutics.

Despite the long history of drug discovery from natural sources, the marine environment, which covers 70% of the Earth's surface, is still relatively unexplored. Intense competition for limited resources drives the evolution of specific and potent chemical defenses distinct from their terrestrial counterparts. Based on this rationale, we recently began screening extracts derived from marine invertebrate and cyanobacterial samples for BACE-1 inhibitors in a chemiluminescent enzyme-fragment complementation (EFC) assay.

Dietary patterns and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort.

We examined dietary patterns and the risk of non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort, which includes more than 215,000 Caucasians, African-Americans, Japanese-Americans, Native Hawaiians, and Latinos aged 45-75 at baseline. All subjects completed a validated food-frequency questionnaire. After a median follow-up time of 10 years, we identified 939 incident NHL cases through linkages with tumor registries.

Dietary vitamin D and risk of non-Hodgkin lymphoma: the multiethnic cohort.

The present study explored the association between dietary vitamin D and non-Hodgkin's lymphoma (NHL) risk. The multiethnic cohort (MEC) includes more than 215 000 Caucasians, African Americans, Native Hawaiians, Japanese Americans and Latinos, aged 45-75. After 10 years of follow-up, 939 incident NHL cases were identified.

Common immune-related risk factors and incident non-Hodgkin lymphoma: the multiethnic cohort.

Severe immune dysfunction is an established risk factor of lymphoma, but the role of moderate alterations of immunity is not clear and prospective investigations are needed. We examined several immune-related disorders and medications in relation to non-Hodgkin lymphoma (NHL) in the Multiethnic Cohort. Over 215,000 subjects of African American, Caucasian, Japanese American, Latino and Native Hawaiian ancestry aged 45-75 years completed a questionnaire, including information on medical history, in 1993-1996.

Phytoestrogenic isoflavonoids in epidemiologic and clinical research.

Isoflavones (IFLs) are natural products to which humans have been traditionally exposed predominantly through soy foods; more recently humans are also exposed to them through soy protein addition to processed foods or through supplements. They are structurally similar to steroidal estrogens and can exert estrogenic or antiestrogenic effects depending on their concentrations and on the tissue considered. These properties qualify IFLs to be classified as phytoestrogens and are believed to account for many of the biological effects observed for soy and/or IFL exposure including benefits for bone and heart health or prevention of menopausal symptoms and certain types of cancer.

Proteasome inhibitors in pediatric cancer treatment.

The 26S proteasome regulates the degradation of many proteins involved in cell cycle control, apoptosis, and tumor growth. The inhibition of the proteasome by specific inhibitors is a viable target for anti-tumor therapy Most prominently, the proteasome inhibitor bortezomib (Velcade) was approved by the U.S.

The association of glycemic load and carbohydrate intake with colorectal cancer risk in the Multiethnic Cohort Study.

Background: High-glycemic-load diets may increase colorectal cancer risk through hyperinsulinemic effects.

Objective: We analyzed data for 191,004 participants in the Multiethnic Cohort Study to determine the risk of colorectal cancer associated with glycemic load (GL), carbohydrate, and sucrose and to ascertain whether this risk was modified by sex and ethnicity.

Design: During 8 y of follow-up, 2379 incident cases of colorectal adenocarcinoma occurred.

Urinary isoflavones are increased in adults, but decreased in children, consuming soy when on oral antibiotic therapy.

The goal of this study was to evaluate how oral antibiotics (OABX) change the appearance of isoflavones (IFLs) in adults and children after soy consumption. The urinary IFL excretion rate (UIER) known to reflect circulating IFLs was hypothesized to change due to intestinal microflora changes by OABX. Subjects provided urine collections in pairs of a baseline urine and an overnight urine before and after consuming soy nuts first during OABX treatment and then again when healthy.