Regulatory Impact of Selected U.S. FDA Postmarketing Safety Registries Conducted for Drugs Used to Treat Inflammatory or Autoimmune Conditions.

Purpose: Assess the regulatory impact of selected FDA postmarketing safety registries on drug product labeling updates.

Methods: Postmarketing safety studies were identified in internal record repositories for the Center for Drug Evaluation and Research, U.S.

Trends in oral and vaginally administered estrogen use among US women 50 years of age or older with commercial health insurance.

Objective: We aimed to provide information through 2015 about use in the United States of estrogen products, including orally and vaginally administered products, in postmenopausal women.

Methods: We used prescription claims for US commercial health insurance to calculate, in women 50 years of age or older (n = 12,007,364), the age-standardized and age-specific annual prevalence of estrogen use, by formulation and route of administration, for the period 2006 through 2015.

Results: The age-standardized annual prevalence of a prescription claim for oral estrogens declined over time, from 83 per 1,000 women in 2007 to 42 per 1,000 women in 2015.

Pesticide exposure and liver cancer: a review.

Purpose: To review the epidemiologic literature examining pesticide exposure and liver cancer incidence.

Methods: A search of the MEDLINE and Embase databases was conducted in October 2015. Eligibility criteria included examining hepatocellular carcinoma (HCC) or primary liver cancer, pesticides as an exposure of interest, and individual-level incidence.

A prospective and retrospective analysis of smoking behavior changes in ever smokers with high risk for lung cancer from New Mexico and Pennsylvania.

Cigarette smoking is the leading preventable cause of death worldwide. The aim of this study is to conduct a prospective and retrospective analysis of smoking behavior changes in the Lovelace Smokers Cohort (LSC) and the Pittsburgh Lung Screening Study cohort (PLuSS). Area under the curve (AUC) for risk models predicting relapse based on demographic, smoking, and relevant clinical variables was 0.

Expression of PAM50 Genes in Lung Cancer: Evidence that Interactions between Hormone Receptors and HER2/HER3 Contribute to Poor Outcome.

Non-small cell lung cancers (NSCLCs) frequently express estrogen receptor (ER) β, and estrogen signaling is active in many lung tumors. We investigated the ability of genes contained in the prediction analysis of microarray 50 (PAM50) breast cancer risk predictor gene signature to provide prognostic information in NSCLC. Supervised principal component analysis of mRNA expression data was used to evaluate the ability of the PAM50 panel to provide prognostic information in a stage I NSCLC cohort, in an all-stage NSCLC cohort, and in The Cancer Genome Atlas data.

Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data.

Background: Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. U.S.

Lung Cancer Risk Prediction Using Common SNPs Located in GWAS-Identified Susceptibility Regions.

Introduction: Genome-wide association studies (GWAS) have consistently identified specific lung cancer susceptibility regions. We evaluated the lung cancer-predictive performance of single-nucleotide polymorphisms (SNPs) in these regions.

Methods: Lung cancer cases (N = 778) and controls (N = 1166) were genotyped for 77 SNPs located in GWAS-identified lung cancer susceptibility regions.

Linking pesticides and human health: a geographic information system (GIS) and Landsat remote sensing method to estimate agricultural pesticide exposure.

Accurate pesticide exposure estimation is integral to epidemiologic studies elucidating the role of pesticides in human health. Humans can be exposed to pesticides via residential proximity to agricultural pesticide applications (drift). We present an improved geographic information system (GIS) and remote sensing method, the Landsat method, to estimate agricultural pesticide exposure through matching pesticide applications to crops classified from temporally concurrent Landsat satellite remote sensing images in California.

Epigenetic Repression of CCDC37 and MAP1B Links Chronic Obstructive Pulmonary Disease to Lung Cancer.

Introduction: Lung cancer and chronic obstructive pulmonary disease (COPD) share environmental risk factors. COPD also increases the risk of lung cancer; however, the molecular mechanisms are unclear.

Methods: An epigenome-wide association study of lung tumors and cancer-free lung tissue (CFLT) pairs from non-small-cell lung cancer cases with (n = 18) or without (n = 17) COPD was conducted using the HumanMethylation450 beadchip (HM450K).

Indolent, Potentially Inconsequential Lung Cancers in the Pittsburgh Lung Screening Study.

Rationale: The finding of indolent, potentially inconsequential cancers (overdiagnosis) is inherent to cancer screening in general, and there is a growing body of literature about this concept in lung cancer screening.

Objectives: We report on indolent, potentially inconsequential lung cancers in the Pittsburgh Lung Screening Study (PLuSS) population screened for lung cancer with annual low-dose computed tomography.

Methods: We identified 93 subjects with screen-detected prevalence cancers in PLuSS.

A simple model for predicting lung cancer occurrence in a lung cancer screening program: The Pittsburgh Predictor.

Background: A user-friendly method for assessing lung cancer risk may help standardize selection of current and former smokers for screening. We evaluated a simple 4-factor model, the Pittsburgh Predictor, against two well-known, but more complicated models for predicting lung cancer risk.

Methods: Trained against outcomes observed in the National Lung Screening Trial (NLST), the Pittsburgh Predictor used four risk factors, duration of smoking, smoking status, smoking intensity, and age, to predict 6-year lung cancer incidence.

Differential expression of circulating microRNAs according to severity of colorectal neoplasia.

There is a need to develop a colorectal cancer (CRC) screening test that is noninvasive, cost effective, and sensitive enough to detect preneoplastic lesions. This case-control study examined the feasibility of using circulating extracellular microRNAs (miRNAs) to differentiate a spectrum of colorectal neoplasia of various severity and hence for early detection of colorectal neoplasia. Archived serum samples of 10 normal controls and 31 cases, including 10 with nonadvanced adenoma, 10 with advanced adenoma, and 11 with CRC, were profiled for circulating miRNAs using next-generation sequencing.

15q12 variants, sputum gene promoter hypermethylation, and lung cancer risk: a GWAS in smokers.

Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Detection of promoter hypermethylation of tumor suppressor genes in exfoliated cells from the lung provides an assessment of field cancerization that in turn predicts lung cancer. The identification of genetic determinants for this validated cancer biomarker should provide novel insights into mechanisms underlying epigenetic reprogramming during lung carcinogenesis.

Improving selection criteria for lung cancer screening. The potential role of emphysema.

Rationale: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity.

Objectives: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion.

Human herpesvirus 8 seroconversion in a population-based cohort of men in Tobago.

Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to <22.

Incidence of head and neck squamous cell carcinoma among subjects at high risk of lung cancer: results from the Pittsburgh Lung Screening Study.

Background: Earlier detection and diagnosis of head and neck squamous cell carcinoma (HNSCC) should lead to improved outcomes. However, to the authors' knowledge, no effective screening strategy has been identified to date. In the current study, the authors evaluated whether it would be useful to screen subjects targeted for lung cancer screening for HNSCC as well.

Lung cancer in patients with chronic obstructive pulmonary disease. Development and validation of the COPD Lung Cancer Screening Score.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) are at high risk for lung cancer (LC) and represent a potential target to improve the diagnostic yield of screening programs.

Objectives: To develop a predictive score for LC risk for patients with COPD.

Methods: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) and the Pittsburgh Lung Screening Study (PLuSS) databases were analyzed.

Identification of epidermal growth factor receptor (EGFR) genetic variants that modify risk for head and neck squamous cell carcinoma.

EGFR polymorphisms have not been thoroughly evaluated for association with head and neck squamous cell carcinoma (HNSCC) risk. We genotyped 578 HNSCC patients and 588 cancer-free controls for 60 EGFR single nucleotide polymorphisms (SNPs) and tested associations with HNSCC risk. EGFR intronic SNPs rs12535536, rs2075110, rs1253871, rs845561 and rs6970262 and synonymous SNP rs2072454 were associated with HNSCC risk among all subjects (p < 0.

Prognosis and conditional disease-free survival among patients with ovarian cancer.

Purpose: Traditional disease-free survival (DFS) does not reflect changes in prognosis over time. Conditional DFS accounts for elapsed time since achieving remission and may provide more relevant prognostic information for patients and clinicians. This study aimed to estimate conditional DFS among patients with ovarian cancer and to evaluate the impact of patient characteristics.

Inherited variation in the ATP-binding cassette transporter ABCB1 and survival after chemotherapy for stage III-IV lung cancer.

Background: The ATP-binding cassette transporter gene ABCB1 and the glutathione S-transferase gene GSTP1 code for a multidrug resistance protein and for a detoxifying phase II metabolic enzyme, respectively, with substrate specificities that include chemotherapy drugs often used to treat lung cancer.

Methods: We genotyped 11 ABCB1 and eight GSTP1 single nucleotide polymorphisms (SNPs) in 698 white lung cancer patients (all current or former cigarette smokers) and used log-rank test statistics and proportional hazards regression to evaluate associations between SNP genotype and survival.

Results: Using data from all 698 cases, one SNP in ABCB1 (rs2235013) was statistically significantly associated with overall survival (p = 0.

Validation of a blood protein signature for non-small cell lung cancer.

Background: CT screening for lung cancer is effective in reducing mortality, but there are areas of concern, including a positive predictive value of 4% and development of interval cancers. A blood test that could manage these limitations would be useful, but development of such tests has been impaired by variations in blood collection that may lead to poor reproducibility across populations.

Results: Blood-based proteomic profiles were generated with SOMAscan technology, which measured 1033 proteins.

COPD phenotypes in a lung cancer screening population.

Background And Aims: COPD (chronic obstructive pulmonary disease) is a very heterogeneous disease, and phenotypic categorization of a high-risk population has many potential benefits. The present study uses a symptom questionnaire, low-dose computed tomography (LDCT) and pulmonary function tests (PFT) to phenotypically subgroup a high-risk population.

Methods: Study group consisted of current or former smokers who underwent lung cancer screening with LDCT as a subgroup of Pittsburgh Lung Screening Study.

Dietary iron, iron homeostatic gene polymorphisms and the risk of advanced colorectal adenoma and cancer.

Dietary iron intake and variation in iron homeostasis genes may affect colorectal neoplasia risk. We conducted two nested case-control studies within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: one of advanced colorectal adenoma (1205 cases; 1387 controls) and one of colorectal cancer (370 cases; 401 controls). Iron intake was estimated with a food frequency questionnaire and genotyping was performed for 21 genes.

Increased methylation of lung cancer-associated genes in sputum DNA of former smokers with chronic mucous hypersecretion.

Background: Chronic mucous hypersecretion (CMH) contributes to COPD exacerbations and increased risk for lung cancer. Because methylation of gene promoters in sputum has been shown to be associated with lung cancer risk, we tested whether such methylation was more common in persons with CMH.

Methods: Eleven genes commonly silenced by promoter methylation in lung cancer and associated with cancer risk were selected.