Effects of deceptive self-reports of quitting on the results of treatment trials for smoking: A quantitative assessment

Problems with self-report measures for smoking motivate the use of biochemical tests in treatment trials for smoking. These biochemical tests, unfortunately, are not perfect. In this paper, we present an algebraic model of bias in treatment trials for smoking. Bias is expressed in terms of the deception rate among continued smokers in a control group, the relative deception rate among continued smokers in an experimental group, and the sensitivity and specificity of a biochemical test which may be used either to confirm self-reports of,quitting or to replace self-report entirely. For given test specificity and sensitivity, the mode) defines deception rates for which different biochemical testing strategies are preferred. The model is presented in the context of current knowledge on the phenomenon of deception among adult smokers. The paper concludes that better judgements regarding the role of biochemical tests in treatment trials for smoking require more precise information regarding the magnitude and determinants of deception.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28158/1/0000610.pd

A case-cohort study of human herpesvirus 8 seropositivity and incident prostate cancer in Tobago

<p>Abstract</p> <p>Background</p> <p>We previously reported a cross-sectional association between the presence of human herpesvirus 8 (HHV-8) serum antibodies and screen-detected prostate cancer in men living in Tobago. In the same study population, we examined the association between HHV-8 seropositivity and incident prostate cancer discovered at later screenings.</p> <p>Methods</p> <p>In 40-81 year-old men without prostate cancer discovered at initial digital rectal examination (DRE) and prostate-specific antigen (PSA) screening, a case-cohort design measured the association between baseline HHV-8 seropositivity (modified immunofluorescence assay for antibodies against HHV-8 lytic antigens) and incident prostate cancer detected at DRE and PSA screenings three or five years later.</p> <p>Results</p> <p>Analyses included 486 unique individuals, 96 incident prostate cancer cases, and 415 randomly selected subjects representing an at-risk cohort. By design, the random sub-cohort contained 25 incident prostate cancer cases. In the sub-cohort, the frequency of HHV-8 seropositivity increased across age groupings (40-49 years: 3.5%, 50-59 years: 13.6%, and ≥ 60 years: 22.9%). HHV-8 seropositivity was higher in men with elevated (≥ 4.0 ng/mL) than men with non-elevated PSA at initial screening (30.4% <it>vs</it>. 9.9% seropositive; crude odds ratio (OR) 3.96, 95% confidence interval (CI) 1.53-10.2; age-adjusted OR 2.42, 95% CI 0.91-6.47). HHV-8 seropositivity did not increase incident prostate cancer risk (age-adjusted hazard ratio (HR) 0.88, 95% CI 0.46-1.69).</p> <p>Conclusions</p> <p>Case-cohort analysis did not identify association between HHV-8 seropositivity and incident prostate cancer. However, analyses uncovered possible association between HHV-8 and PSA (a marker of prostate inflammation). Co-occurrence of HHV-8 seropositivity and PSA elevation may explain cross-sectional association between HHV-8 and PSA screen-detected prostate cancer.</p

Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer

Lung cancer is the leading cause of cancer deaths, because ~84% of cases are diagnosed at an advanced stage. Worldwide in 2008, ~1.5 million people were diagnosed and ~1.3 million died &#x2013; a survival rate unchanged since 1960. However, patients diagnosed at an early stage and have surgery experience an 86% overall 5-year survival. New diagnostics are therefore needed to identify lung cancer at this stage. Here we present the first large scale clinical use of aptamers to discover blood protein biomarkers in disease with our breakthrough proteomic technology. This multi-center case-control study was conducted in archived samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. We measured &#x3e;800 proteins in 15uL of serum, identified 44 candidate biomarkers, and developed a 12-protein panel that distinguished NSCLC from controls with 91% sensitivity and 84% specificity in a training set and 89% sensitivity and 83% specificity in a blinded, independent verification set. Performance was similar for early and late stage NSCLC. This is a significant advance in proteomics in an area of high clinical need

Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies indicate that some characteristics of lung cancer among never-smokers significantly differ from those of smokers. Aberrant promoter methylation and mutations in some oncogenes and tumor suppressor genes are frequent in lung tumors from smokers but rare in those from never-smokers. In this study, we analyzed promoter methylation in the <it>ras-association domain isoform A (RASSF1A) </it>and the <it>death-associated protein kinase (DAPK) </it>genes in lung tumors from patients with primarily non-small cell lung cancer (NSCLC) from the Western Pennsylvania region. We compare the results with the smoking status of the patients and the mutation status of the K-<it>ras</it>, <it>p53</it>, and <it>EGFR </it>genes determined previously on these same lung tumors.</p> <p>Methods</p> <p>Promoter methylation of the <it>RASSF1A </it>and <it>DAPK </it>genes was analyzed by using a modified two-stage methylation-specific PCR. Data on mutations of K-<it>ras</it>, <it>p53</it>, and <it>EGFR </it>were obtained from our previous studies.</p> <p>Results</p> <p>The <it>RASSF1A </it>gene promoter methylation was found in tumors from 46.7% (57/122) of the patients and was not significantly different between smokers and never-smokers, but was associated significantly in multiple variable analysis with tumor histology (p = 0.031) and marginally with tumor stage (p = 0.063). The <it>DAPK </it>gene promoter methylation frequency in these tumors was 32.8% (40/122) and did not differ according to the patients' smoking status, tumor histology, or tumor stage. Multivariate analysis adjusted for age, gender, smoking status, tumor histology and stage showed that the frequency of promoter methylation of the <it>RASSF1A </it>or <it>DAPK </it>genes did not correlate with the frequency of mutations of the K<it>-ras, p53</it>, and <it>EGFR </it>gene.</p> <p>Conclusion</p> <p>Our results showed that <it>RASSF1A </it>and <it>DAPK </it>genes' promoter methylation occurred frequently in lung tumors, although the prevalence of this alteration in these genes was not associated with the smoking status of the patients or the occurrence of mutations in the K-<it>ras</it>, <it>p53 </it>and <it>EGFR </it>genes, suggesting each of these events may represent independent event in non-small lung tumorigenesis.</p

The Influence of Radiographic Phenotype and Smoking Status on Peripheral Blood Biomarker Patterns in Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is characterized by both airway remodeling and parenchymal destruction. The identification of unique biomarker patterns associated with airway dominant versus parenchymal dominant patterns would support the existence of unique phenotypes representing independent biologic processes. A cross-sectional study was performed to examine the association of serum biomarkers with radiographic airway and parenchymal phenotypes of COPD. Methodology/Principal Findings: Serum from 234 subjects enrolled in a CT screening cohort was analyzed for 33 cytokines and growth factors using a multiplex protein array. The association of serum markers with forced expiratory volume in one second percent predicted (FEV1%) and quantitative CT measurements of airway thickening and emphysema was assessed with and without stratification for current smoking status. Significant associations were found with several serum inflammatory proteins and measurements of FEV1%, airway thickening, and parenchymal emphysema independent of smoking status. The association of select analytes with airway thickening and emphysema was independent of FEV1%. Furthermore, the relationship between other inflammatory markers and measurements of physiologic obstruction or airway thickening was dependent on current smoking status. Conclusions/Significance: Airway and parenchymal phenotypes of COPD are associated with unique systemic serum biomarker profiles. Serum biomarker patterns may provide a more precise classification of the COPD syndrome, provide insights into disease pathogenesis and identify targets for novel patient-specific biological therapies. © 2009 Bon et al

Genome-Wide Association Study of Relative Telomere Length

Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = −0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Childhood passive smoke exposure is associated with adult head and neck cancer

IntroductionPassive smoke is carcinogenic but its association with head and neck squamous cell carcinoma (HNSCC) is uncertain.MethodsWe conducted a case-control study of childhood passive smoke exposure (CPSE) and HNSCC in 858 cases and 806 frequency-matched controls using an interviewer-administered questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression controlling for adult smoking in the total study population, and in never-smokers only (184 cases and 415 controls). CPSE was also studied in oropharyngeal separately from other HNSCC using polytomous logistic regression.ResultsCPSE was associated with HNSCC (OR, 1.28; 95% CI, 1.01-1.63) after controlling for adult smoking and other factors. This association was similar in magnitude, although not statistically significant, among subjects who never smoked as adults (OR, 1.19, 95% CI, 0.80-1.76). CPSE was associated more strongly with oropharyngeal cancer (a HNSCC subtype commonly associated with human papillomavirus (HPV) infection) than with HNSCC at non-oropharyngeal sites (OR, 2.02; 95% CI, 1.01-4.06, N=52 cases vs. OR, 1.04; 95% CI, 0.68-1.60, N=132 cases; P-for-heterogeneity=0.08).ConclusionsData from this large US-based case control study suggest a role for CPSE in HNSCC etiology