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Hpg80 (Circulating Progastrin), A Novel Blood-Based Biomarker For Detection Of Poorly Differentiated Neuroendocrine Carcinoma And Well Differentiated Neuroendocrine Tumors, Aman Chauhan, Alexandre Prieur, Jill Kolesar, Susanne Arnold, Léa Payen, Younes Mahi, Berengere Vire, Madison Sands, B. Mark Evers, Dominique Joubert, Lowell Anthony

Markey Cancer Center Faculty Publications

Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG₈₀) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG₈₀ in NENs. Plasma hPG₈₀ was quantified from 95 stage IV NEN patients, using DxPG₈₀ technology (ECS Progastrin, Switzerland) and compared with hPG₈₀ concentrations in two cohorts of healthy donor controls aged 50–80 (n = 252) and 18–25 (n = 137). Median hPG₈₀ in NENs patients was 5.54 pM compared to 1.5 pM for the …

Through The Lens: Youth Experiences With Cancer In Rural Appalachian Kentucky Using Photovoice, Katie Gaines, Courtney Martin, Chris Prichard, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Rural Appalachian Kentucky experiences disproportionately high cancer incidence and mortality rates. This cancer burden is due to social determinants of health and cultural factors prominent in the region. The firsthand experiences of community members—especially young people—can highlight these factors and identify areas for improvement. The purpose of this study was to encourage Appalachian Kentucky youth to consider determinants of cancer and visualize the effects that cancer has on their families or communities by asking them to take photographs of cancer-related objects around them. Content analysis was performed on 238 photographs submitted by 25 students, and photographs were organized into themes, …

Enhancing Cancer Care Of Rural Dwellers Through Telehealth And Engagement (Encore): Protocol To Evaluate Effectiveness Of A Multi-Level Telehealth-Based Intervention To Improve Rural Cancer Care Delivery, Tuya Pal, Pamela C. Hull, Tatsuki Koyama, Phillip Lammers, Denise Martinez, Jacob Mcarthy, Emma Schremp, Ann Tezak, Anne Washburn, Jennifer G. Whisenant, Debra L. Friedman

Markey Cancer Center Faculty Publications

BACKGROUND: Despite lower cancer incidence rates, cancer mortality is higher among rural compared to urban dwellers. Patient, provider, and institutional level factors contribute to these disparities. The overarching objective of this study is to leverage the multidisciplinary, multispecialty oncology team from an academic cancer center in order to provide comprehensive cancer care at both the patient and provider levels in rural healthcare centers. Our specific aims are to: 1) evaluate the clinical effectiveness of a multi-level telehealth-based intervention consisting of provider access to molecular tumor board expertise along with patient access to a supportive care intervention to improve cancer care …

Egfr Testing And Erlotinib Use In Non-Small Cell Lung Cancer Patients In Kentucky, Kara L. Larson, Bin Huang, Quan Chen, Thomas C. Tucker, Marissa Schuh, Susanne M. Arnold, Jill M. Kolesar

Markey Cancer Center Faculty Publications

This study determined the frequency and factors associated with EGFR testing rates and erlotinib treatment as well as associated survival outcomes in patients with non small cell lung cancer in Kentucky. Data from the Kentucky Cancer Registry (KCR) linked with health claims from Medicaid, Medicare and private insurance groups were evaluated. EGFR testing and erlotinib prescribing were identified using ICD-9 procedure codes and national drug codes in claims, respectively. Logistic regression analysis was performed to determine factors associated with EGFR testing and erlotinib prescribing. Cox-regression analysis was performed to determine factors associated with survival. EGFR mutation testing rates rose from …

A Brief Educational Intervention Enhances Basic Cancer Literacy Among Kentucky Middle And High School Students, Lauren Hudson, Kerrigan M. Samons, Haley E. Dicken, Chris Prichard, L. Todd Weiss, Jean Edward, Robin C. Vanderpool, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky experiences the highest overall cancer incidence and mortality rates in the USA with the greatest burden in the eastern, Appalachian region of the state. Cancer disparities in Kentucky are driven in part by poor health behaviors, poverty, lack of health care access, low education levels, and low health literacy. Individuals with inadequate health literacy are less likely to participate in preventive measures such as obtaining screenings and making healthy lifestyle choices, thus increasing their chances of developing and dying from cancer. By increasing cancer literacy among youth and adults, it may be possible to decrease cancer disparities across Kentucky. …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Genetic Interaction Analysis Among Oncogenesis-Related Genes Revealed Novel Genes And Networks In Lung Cancer Development, Yafang Li, Xiangjun Xiao, Yohan Bossé, Olga Gorlova, Ivan Gorlov, Younghun Han, Jinyoung Byun, Natasha Leighl, Jakob S. Johansen, Matt Barnett, Chu Chen, Gary Goodman, Angela Cox, Fiona Taylor, Penella Woll, H. Erich Wichmann, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Jiali Han, Katherine Siminovitch, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria

Markey Cancer Center Faculty Publications

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified …

Identification Of Susceptibility Pathways For The Role Of Chromosome 15q25.1 In Modifying Lung Cancer Risk, Xuemei Ji, Yohan Bossé, Maria Teresa Landi, Jiang Gui, Xiangjun Xiao, David Qian, Philippe Joubert Joubert, Maxime Lamontagne, Yafang Li, Ivan Gorlov, Mariella De Biasi, Younghun Han, Olga Gorlova, Rayjean J. Hung, Xifeng Wu, James Mckay, Xuchen Zong, Robert Carreras-Torres, David C. Christiani, Neil Caporaso, Mattias Johansson, Geoffrey Liu, Stig E. Bojesen, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C. Aldrich, William S. Bush, Adonina Tardon, Gad Rennert, Susanne M. Arnold

Markey Cancer Center Faculty Publications

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated …

Geographical, Racial And Socio-Economic Variation In Life Expectancy In The Us And Their Impact On Cancer Relative Survival, Angela B. Mariotto, Zhaohui Zou, Christopher J. Johnson, Steve Scoppa, Hannah K. Weir, Bin Huang

Markey Cancer Center Faculty Publications

Purpose

Despite gains in life expectancy between 1992 to 2012, large disparities in life expectancy continue to exist in the United States between subgroups of the population. This study aimed to develop detailed life tables (LT), accounting for mortality differences by race, geography, and socio-economic status (SES), to more accurately measure relative cancer survival and life expectancy patterns in the United States.

Methods

We estimated an extensive set of County SES-LT by fitting Poisson regression models to deaths and population counts for U.S. counties by age, year, gender, race, ethnicity and county-level SES index. We reported life expectancy patterns and …

Global Burden Of Neuroendocrine Tumors And Changing Incidence In Kentucky, Aman Chauhan, Qian Yu, Neha Ray, Zainab Farooqui, Bin Huang, Eric B. Durbin, Thomas Tucker, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

Background: Neuroendocrine tumors (NETs) have a low incidence but relatively high prevalence. Over the last three decades, the incidence of NETs has risen 6-fold in the United States. We conducted an observational study to compare the incidence of NETs reported to the Kentucky Cancer Registry (KCR) versus that reported to Surveillance, Epidemiology, and End Results Program (SEER). We also provide a systematic review of the state of neuroendocrine tumors worldwide, and compare the available global and local published data.

Methods: KCR and SEER databases were queried for NET cases between 1995 and 2015. A detailed literature review of epidemiological data …

The Value Of Mri In Distinguishing Subtypes Of Lipomatous Extremity Tumors Needs Reassessment In The Era Of Mdm2 And Cdk4 Testing, Sean Ryan, Julia Visgauss, David Kerr, Joshua Helmkamp, Nicholas Said, Emily Vinson, Patrick W. O'Donnell, Xuechan Li, Sin-Ho Jung, Diana Cardona, William Eward, Brian Brigman

Markey Cancer Center Faculty Publications

Introduction. Extremity lipomas and well-differentiated liposarcomas (WDLs) are difficult to distinguish on MR imaging. We sought to evaluate the accuracy of MRI interpretation using MDM2 amplification, via fluorescence in-situ hybridization (FISH), as the gold standard for pathologic diagnosis. Furthermore, we aimed to investigate the utility of a diagnostic formula proposed in the literature. Methods. We retrospectively collected 49 patients with lipomas or WDLs utilizing MDM2 for pathologic diagnosis. Four expert readers interpreted each patient's MRI independently and provided a diagnosis. Additionally, a formula based on imaging characteristics (i.e. tumor depth, diameter, presence of septa, and internal cystic change) …

Superficial Soft-Tissue Sarcomas Rarely Require Advanced Soft-Tissue Reconstruction Following Resection, William C. Eward, Alexander L. Lazarides, Anthony M. Griffin, Patrick W. O'Donnell, Amir Sternheim, Anne O'Neill, Stefan O. Hofer, Peter C. Ferguson, Jay S. Wunder

Markey Cancer Center Faculty Publications

Objective: Soft-tissue sarcomas are most frequently located deep within myofascial compartments. Superficial soft-tissue sarcomas (S-STS) are relatively less common and may be managed differently than deep sarcomas because generous resection margins are often possible without sacrificing critical structures. We sought to investigate the frequency and types of soft-tissue reconstructive procedures that are required following excision of S-STS.

Methods: We reviewed 457 consecutively treated patients with S-STS with a minimum 2-year follow-up from our prospectively maintained database between 1989 and 2009.

Results: Mean follow-up was 10.5 years (range, 2–23). Four hundred twenty-one tumors (91%) were excised with negative margins, 38 (8.3%) …

Comprehensive Genomic Profiling In Routine Clinical Practice Leads To A Low Rate Of Benefit From Genotype-Directed Therapy, Talal Hilal, Mary Nakazawa, Jacob Hodskins, John L. Villano, Aju Mathew, Gaurav Goel, Lars M. Wagner, Susanne M. Arnold, Philip Desimone, Lowell B. Anthony, Peter J. Hosein

Markey Cancer Center Faculty Publications

Background: Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.

Methods: Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.

Results: A total of 125 pediatric …

Frameless Image-Guided Radiosurgery For Trigeminal Neuralgia, Lisa B. E. Shields, Todd S. Shanks, Andrew J. Shearer, Lauren A. Shelton, Brent J. Shelton, Jonathan Howe, James M. Coons, Brian Plato, Aaron C. Spalding

Markey Cancer Center Faculty Publications

Background: Frameless image-guided radiosurgery (IGRS) is a safe and effective noninvasive treatment for trigeminal neuralgia (TN). This study evaluates the use of frameless IGRS to treat patients with refractory TN.

Methods: We reviewed the records of 20 patients diagnosed with TN who underwent frameless IGRS treatments between March 2012 and December 2013. Facial pain was graded using the Barrow Neurological Institute (BNI) scoring system. The initial setup uncertainty from simulation to treatment and the patient intrafraction uncertainty were measured. The median follow-up was 32 months.

Results: All patients' pain was BNI Grade IV or V before the frameless IGRS treatment. …

Phase Iii Prospective Randomized Comparison Trial Of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab In Patients With Advanced Carcinoid Tumors: Swog S0518, James C. Yao, Katherine A. Guthrie, Cesar Moran, Jonathan R. Strosberg, Matthew H. Kulke, Jennifer A. Chan, Noelle Loconte, Robert R. Mcwilliams, Edward M. Wolin, Bassam Mattar, Shannon Mcdonough, Helen Chen, Charles D. Blanke, Howard S. Hochster

Markey Cancer Center Faculty Publications

Purpose

Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs.

Patients and Methods

Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary …

Incidence Of Cns Tumors In Appalachian Children, Bin Huang, Alice Luo, Eric B. Durbin, Ellen Lycan, Thomas Tucker, Quan Chen, Craig Horbinski, John L. Villano

Markey Cancer Center Faculty Publications

Determine whether the risk of astrocytomas in Appalachian children is higher than the national average. We compared the incidence of pediatric brain tumors in Appalachia versus non-Appalachia regions, covering years 2000–2011. The North American Association of Central Cancer Registries (NAACCR) collects population-based data from 55 cancer registries throughout U.S. and Canada. All invasive primary (i.e. non-metastatic tumors), with age at diagnosis 0–19 years old, were included. Nearly 27,000 and 2200 central nervous system (CNS) tumors from non-Appalachia and Appalachia, respectively comprise the cohorts. Age-adjusted incidence rates of each main brain tumor subtype were compared. The incidence rate of pediatric CNS …

Phase 3 Trial Of 177Lu-Dotatate For Midgut Neuroendocrine Tumors, Jonathan Strosberg, Ghassan El-Haddad, Edward M. Wolin, Andrew Hendifar, James Yao, Beth Chasen, Erik Mittra, Pamela L. Kunz, Matthew H. Kulke, Heather Jacene, David Bushnell, Thomas M. O’Dorisio, Richard P. Baum, Harshad R. Kulkarni, Martyn Caplin, Rachida Lebtahi, Timothy Hobday, Ebrahim Delpassand, Eric Van Cutsem, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaime Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore Seregni, Kjell Öberg, Maribel Lopera Sierra, Paola Santoro

Markey Cancer Center Faculty Publications

BACKGROUND

Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (¹⁷⁷Lu)–Dotatate in patients with advanced, progressive, somatostatin-receptor–positive midgut neuroendocrine tumors.

METHODS

We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either ¹⁷⁷Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (¹⁷⁷Lu-Dotatate group) or octreotide LAR …

Differences And Similarities In The Clinicopathological Features Of Pancreatic Neuroendocrine Tumors In China And The United States: A Multicenter Study, Li-Ming Zhu, Laura Tang, Xin-Wei Qiao, Edward M. Wolin, Nicholas N. Nissen, Deepti Dhall, Jie Chen, Lin Shen, Yihebali Chi, Yao-Zong Yuan, Qi-Wen Ben, Bin Lv, Ya-Ru Zhou, Chun-Mei Bai, Jie Chen, Yu-Li Song, Tian-Tian Song, Chong-Mei Lu, Run Yu, Yuan-Jia Chen

Markey Cancer Center Faculty Publications

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria.

This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based …

Plasma Tnf-Α And Soluble Tnf Receptor Levels After Doxorubicin With Or Without Co-Administration Of Mesna-A Randomized, Cross-Over Clinical Study, John Hayslip, Emily Van Meter Dressler, Heidi L. Weiss, Tammy J. Taylor, Mara D. Chambers, Teresa Noel, Sumitra Miriyala, Jeriel T. R. Keeney, Xiaojia Ren, Rukhsana Sultana, Mary Vore, D. Allan Butterfield, Daret St. Clair, Jeffrey A. Moscow

Markey Cancer Center Faculty Publications

PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a common sequelae of cancer therapy. Recent preclinical observations have suggested that CICI can be mediated by chemotherapy-induced plasma protein oxidation, which triggers TNF-α mediated CNS damage. This study evaluated sodium-2-mercaptoethane sulfonate (Mesna) co-administration with doxorubicin to reduce doxorubicin-induced plasma protein oxidation and resultant cascade of TNF-α, soluble TNF receptor levels and related cytokines.

METHODS: Thirty-two evaluable patients were randomized using a crossover design to receive mesna or saline in either the first or second cycle of doxorubicin in the context of a standard chemotherapy regimen for either non-Hodgkin lymphoma or breast …

Detection Of Phlpp1Α/Β In Human And Mouse Brain By Different Anti-Phlpp1 Antibodies, Travis C. Jackson, Hülya Bayir, Milos D. Ikonomovic, Keri Janesko-Feldman, Zaichuan Mi, Tianyan Gao, Edwin K. Jackson, Patrick M. Kochanek

Markey Cancer Center Faculty Publications

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal …

Ultraviolet Radiation, Aging And The Skin: Prevention Of Damage By Topical Camp Manipulation, Alexandra Amaro-Ortiz, Betty Yan, John A. D’Orazio

Markey Cancer Center Faculty Publications

Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study the long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. …

A Survey Of The Barriers Associated With Academic-Based Cancer Research Commercialization, Nathan L. Vanderford, L. Todd Weiss, Heidi L. Weiss

Markey Cancer Center Faculty Publications

Commercialization within the academic setting is associated with many challenges and barriers. Previous studies investigating these challenges/barriers have, in general, broadly focused on multiple disciplines and, oftentimes, several institutions simultaneously. The goal of the study presented here was to analyze a range of barriers that may be broadly associated with commercializing academic-based cancer research. This goal was addressed via a study of the barriers associated with cancer research commercialization at the University of Kentucky (UK). To this end, a research instrument in the form of an electronic survey was developed. General demographic information was collected on study participants and two …

Adult Bmi Change And Risk Of Colon Cancer In Postmenopausal Women, Lyla Blake-Gumbs, Zhengyi Chen, Cheryl L. Thompson, Nathan A. Berger, Thomas C. Tucker, Li Li

Markey Cancer Center Faculty Publications

Purpose. We recently reported an association of adult BMI change with colon cancer risk. Here, we sought to further explore this association with respect to postmenopausal HRT use in a larger study population. Methods. We included 1,457 postmenopausal women participating in an ongoing population-based case-control study of colon cancer. Results. We confirmed a previously reported association of adulthood weight gain and increased risk of colon cancer: compared to those with <5 kg/m² change of BMI, women who reported moderate (5–10 kg/m²) and large (>10 kg/m²) BMI changes since their 20s had OR estimates …

No Association Of Obesity And Type 2 Diabetes Mellitus Related Genetic Variants With Colon Cancer, Cheryl L. Thompson, Sarah J. Plummer, Thomas C. Tucker, Graham Casey, Li Li

Markey Cancer Center Faculty Publications

Background: Obesity and type 2 diabetes mellitus (T2D) are known risk factors for colon cancer. Recent reports from a number of genome wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with obesity and T2D. Here we tested the hypothesis that these SNPs may also be associated with risk of colon cancer.

Methods: We genotyped nine SNPs reported in GWAS of obesity and/or T2D, including SNPs in HHEX, KCNJ11, SLC30A8, FTO, CDKN2, CDKAL1, TCF2, and the rs9300039 SNP in an intergenic region, in 561 colon cancer cases and 721 population controls.

Results: None of these SNPs were …

Sociodemographic Characteristics And Diabetes Predict Invalid Self-Reported Non-Smoking In A Population-Based Study Of U.S. Adults, Monica A. Fisher, George W. Taylor, Brent J. Shelton, Sara M. Debanne

Markey Cancer Center Faculty Publications

BACKGROUND: Nearly all studies reporting smoking status collect self-reported data. The objective of this study was to assess sociodemographic characteristics and selected, common smoking-related diseases as predictors of invalid reporting of non-smoking. Valid self-reported smoking may be related to the degree to which smoking is a behavior that is not tolerated by the smoker's social group.

METHODS: True smoking was defined as having serum cotinine of 15+ng/ml. 1483 "true" smokers 45+ years of age with self-reported smoking and serum cotinine data from the Mobile Examination Center were identified in the third National Health and Nutrition Examination Survey. Invalid non-smoking was …