Epigenetic Contributions to the Relationship between Cancer and Dietary Intake of Nutrients, Bioactive Food Components, and Environmental Toxicants

Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Cancer is a multistep process derived from combinational crosstalk between genetic alterations and epigenetic influences through various environmental factors. The observation that epigenetic changes are reversible makes them an attractive target for cancer prevention. Until recently, there have been difficulties studying epigenetic mechanisms in interactions between dietary factors and environmental toxicants. The development of the field of cancer epigenetics during the past decade has been advanced rapidly by genome-wide technologies – which initially employed microarrays but increasingly are using high-throughput sequencing – which helped to improve the quality of the analysis, increase the capacity of sample throughput, and reduce the cost of assays. It is particularly true for applications of cancer epigenetics in epidemiologic studies that examine the relationship among diet, epigenetics, and cancer because of the issues of tissue heterogeneity, the often limiting amount of DNA samples, and the significant cost of the analyses. This review offers an overview of the state of the science in nutrition, environmental toxicants, epigenetics, and cancer to stimulate further exploration of this important and developing area of science. Additional epidemiologic research is needed to clarify the relationship between these complex epigenetic mechanisms and cancer

Urinary bisphenol A and age at menarche among adolescent girls: Evidence from NHANES 2003–2010

Bisphenol A (BPA) is an environmental estrogen used in the manufacture of polycarbonate plastics and epoxy resins used to make food and beverage packaging. Increasing evidence suggests that BPA mimics estrogens in the body and may be associated with putative markers of breast cancer risk

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile

Pre- and Postnatal Fine Particulate Matter Exposure and Childhood Cognitive and Adaptive Function

Increasing evidence exists for an association between early life fine particulate matter (PM2.5) exposure and several neurodevelopmental outcomes, including autism spectrum disorder (ASD); however, the association between PM2.5 and adaptive and cognitive function remains poorly understood. Participants included 658 children with ASD, 771 with a non-ASD developmental disorder, and 849 population controls from the Study to Explore Early Development. Adaptive functioning was assessed in ASD cases using the Vineland Adaptive Behavior Scales (VABS); cognitive functioning was assessed in all groups using the Mullen Scales of Early Learning (MSEL). A satellite-based model was used to assign PM2.5 exposure averages during pregnancy, each trimester, and the first year of life. Linear regression was used to estimate beta coefficients and 95% confidence intervals, adjusting for maternal age, education, prenatal tobacco use, race-ethnicity, study site, and season of birth. PM2.5 exposure was associated with poorer VABS scores for several domains, including daily living skills and socialization. Associations were present between prenatal PM2.5 and lower MSEL scores for all groups combined; results were most prominent for population controls in stratified analyses. These data suggest that early life PM2.5 exposure is associated with specific aspects of cognitive and adaptive functioning in children with and without ASD

Thermo-Mechanical Treatment Effects on Stress Relaxation and Hydrogen Embrittlement of Cold-Drawn Eutectoid Steels

The effects of the temperature and stretching levels used in the stress-relieving treatment of cold-drawn eutectoid steel wires are evaluated with the aim of improving the stress relaxation behavior and the resistance to hydrogen embrittlement. Five industrial treatments are studied, combining three temperatures (330, 400, and 460 °C) and three stretching levels (38, 50 and 64% of the rupture load). The change of the residual stress produced by the treatments is taken into consideration to account for the results. Surface residual stresses allow us to explain the time to failure in standard hydrogen embrittlement test

Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial

The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC. Higher PD-L1 IHC and immune pathway scores, but not angiogenesis scores, are associated with greater ramucirumab OS benefit. Additionally, Basal subtypes, which have higher PD-L1 IHC and immune/angiogenesis pathway scores, show greater ramucirumab OS benefit compared to Luminal subtypes, which have relatively lower scores. Multivariable analysis suggests patients from East Asia as having lower immune/angiogenesis signature scores, which correlates with decreased ramucirumab OS benefit. Our data highlight the utility of multiple biomarkers including PD-L1, molecular subtype, and immune phenotype in identifying patients with UC who might derive the greatest benefit from treatment with ramucirumab