Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility.

Cigarette smoking by children and adolescents continues to be prevalent, and this fact represents a major public health problem and challenge. Epidemiologic work has previously suggested that exposure of the lung to tobacco carcinogens at an early age may be an independent risk factor for lung cancer. Recent studies at the molecular and cellular levels are consistent with this, now suggesting that early exposure enhances DNA damage and is associated with the induction of DNA alterations in specific chromosomal regions. In this paper we hypothesize that adolescence, which is known to be the period of greatest development for the lung, may constitute a "critical period" in which tobacco carcinogens can induce fields of genetic alterations that make the early smoker more susceptible to the damaging effects of continued smoking. The fact that lung development differs by sex might also contribute to apparent gender differences in lung cancer susceptibility. Because this hypothesis has important implications for health policy and tobacco control, additional resources need to be devoted to its further evaluation. Targeted intervention in adolescent smoking may yield even greater reductions in lung cancer occurrence than otherwise anticipated

Absence of an embryonic stem cell DNA methylation signature in human cancer.

BackgroundDifferentiated cells that arise from stem cells in early development contain DNA methylation features that provide a memory trace of their fetal cell origin (FCO). The FCO signature was developed to estimate the proportion of cells in a mixture of cell types that are of fetal origin and are reminiscent of embryonic stem cell lineage. Here we implemented the FCO signature estimation method to compare the fraction of cells with the FCO signature in tumor tissues and their corresponding nontumor normal tissues.MethodsWe applied our FCO algorithm to discovery data sets obtained from The Cancer Genome Atlas (TCGA) and replication data sets obtained from the Gene Expression Omnibus (GEO) data repository. Wilcoxon rank sum tests, linear regression models with adjustments for potential confounders and non-parametric randomization-based tests were used to test the association of FCO proportion between tumor tissues and nontumor normal tissues. P-values of < 0.05 were considered statistically significant.ResultsAcross 20 different tumor types we observed a consistently lower FCO signature in tumor tissues compared with nontumor normal tissues, with 18 observed to have significantly lower FCO fractions in tumor tissue (total n = 6,795 tumor, n = 922 nontumor, P < 0.05). We replicated our findings in 15 tumor types using data from independent subjects in 15 publicly available data sets (total n = 740 tumor, n = 424 nontumor, P < 0.05).ConclusionsThe results suggest that cancer development itself is substantially devoid of recapitulation of normal embryologic processes. Our results emphasize the distinction between DNA methylation in normal tightly regulated stem cell driven differentiation and cancer stem cell reprogramming that involves altered methylation in the service of great cell heterogeneity and plasticity

Immune factors preceding diagnosis of glioma: a Prostate Lung Colorectal Ovarian Cancer Screening Trial nested case-control study.

BackgroundEpidemiological studies of adult glioma have identified genetic and environmental risk factors, but much remains unclear. The aim of the current study was to evaluate anthropometric, disease-related, and prediagnostic immune-related factors for relationship with glioma risk.MethodsWe conducted a nested case-control study among the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. One hundred and twenty-four glioma cases were identified and each matched to four controls. Baseline characteristics were collected at enrollment and were evaluated for association with glioma status. Serum specimens were collected at yearly intervals and were analyzed for immune-related factors including TGF-β1, TNF-α, total IgE, and allergen-specific IgE. Immune factors were evaluated at baseline in a multivariate conditional logistic regression model, along with one additional model that incorporated the latest available measurement.ResultsA family history of glioma among first-degree relatives was associated with increased glioma risk (OR = 4.41, P = .002). In multivariate modeling of immune factors at baseline, increased respiratory allergen-specific IgE was inversely associated with glioma risk (OR for allergen-specific IgE > 0.35 PAU/L: 0.59, P = .03). A logistic regression model that incorporated the latest available measurements found a similar association for allergen-specific IgE (P = .005) and showed that elevated TGF-β1 was associated with increased glioma risk (P-value for trend <.0001).ConclusionThe results from this prospective prediagnostic study suggest that several immune-related factors are associated with glioma risk. The association observed for TGF-β1 when sampling closer to the time of diagnosis may reflect the nascent brain tumor's feedback on immune function

Maternal Prenatal Use of Alcohol, Tobacco, and Illicit Drugs and Associations with Childhood Cancer Subtypes.

BACKGROUND: The association between childhood cancer risk and maternal prenatal substance use/abuse remains uncertain due to modest sample sizes and heterogeneous study designs. METHODS: We surveyed parents of children with cancer regarding maternal gestational use of tobacco, alcohol, and illicit drugs, using a Likert-type scale, and demographic, perinatal, and clinical variables. Multivariable log-Poisson regression assessed differences in frequency of prenatal substance use across fifteen childhood cancer subtypes, adjusting for birthweight, gestational age, and demographic factors. RESULTS: Respondents from 3,145 unique families completed the survey (92% biological mothers). A minority reported gestational use of tobacco products (14%), illicit drugs including marijuana or cocaine (4%), or more than a moderate amount of alcohol (2%). Prenatal illicit drug use was associated with increased prevalence of intracranial embryonal tumors [prevalence ratio (PR) = 1.94; confidence interval [CI], 1.05-3.58], including medulloblastoma (PR = 1.82) and supratentorial primitive neuroectodermal tumors (PNET; PR = 2.66), and was also associated with retinoblastoma (PR = 3.11; CI, 1.20-8.08). Moderate to heavy alcohol consumption was strongly associated with elevated prevalence of non-Hodgkin lymphoma (PR = 5.94; CI, 1.84-19.21). Prenatal smoking was not associated with elevated prevalence of any childhood cancer subtype. CONCLUSIONS: We identify novel associations between illicit drug use during pregnancy and increased prevalence of nonglioma central nervous system tumors, including medulloblastoma, supratentorial PNETs, and retinoblastoma. Gestational exposure to alcohol was positively associated with non-Hodgkin lymphoma. IMPACT: Although alcohol and tobacco use during pregnancy has declined, gestational cannabis use has risen. Investigating its impact on neurodevelopment and brain tumorigenesis is vital, with important implications for childhood cancer research and public health education

The Ursinus Weekly, March 11, 1963

Campus Chest activities continue: Plans include student-faculty show, Demas dinner, car wash, penny mile, auction and food sales • PSEA plans film tomorrow evening • UCC region office opens on campus • Staring match named Spring play; Matusow, DeBeer, Murphy in cast • Political film planned tomorrow night by Young Republicans • State to complete repair work on Rt. 422 in Spring • Monday Morning Watch to be held during Lent • Committee on Student Activities gives grants to 18 organizations • ICG convention held Saturday • Archaeologist Gordon speaks at Forum Wednesday night • Dean Pettit to appear in Thursday\u27s Controversy at midnight session • Process underway to select UC\u27s College Bowl team • Ursinus participates in WIP radio series entitled Seminar 610 • Taxation topic of panel discussion held last week • Political intern program offered as Summer work • Editorial: Should the Weekly crusade? • Letters to the editor • Greek gleanings • Power to choose right or wrong is God\u27s gift to man • Hosteling activities lead to exciting experiences • Results of Campus Chest\u27s doubleheader Friday: Men\u27s varsity swamps intramural all-stars 83-40, Women\u27s varsity clobbers faculty all-stars 51-29 • Mermaids defeat Bryn Mawr team • Intramural season comes to a close • Netwomen outplay Immaculata, bow to West Chester • All-star intramural teams namedhttps://digitalcommons.ursinus.edu/weekly/1290/thumbnail.jp