SynthesisJournal of the National Cancer Institute2015
15q12 variants, sputum gene promoter hypermethylation, and lung cancer risk: a GWAS in smokers.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Genome-Wide Association Study of Fluorescent Oxidation Products Accounting for Tobacco Smoking Status in Adults from the French EGEA Study.Antioxidants (Basel, Switzerland) · 2022Article
- Small Airway Wall Thickening Assessed by Computerized Tomography Is Associated With Low Lung Function in Chinese Carbon Black Packers.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Identification of novel epigenetic abnormalities as sputum biomarkers for lung cancer risk among smokers and COPD patients.Lung cancer (Amsterdam, Netherlands) · 2020Article
- The Inhibitory Effect of (-)-Epigallocatechin-3-Gallate on Breast Cancer Progression via ReducingMolecules (Basel, Switzerland) · 2019Article
- Association between IL-4 tagging single nucleotide polymorphisms and the risk of lung cancer in China.Molecular genetics & genomic medicine · 2019Article
- Gene Promoter Hypermethylation Detected in Sputum Predicts FEVAmerican journal of respiratory and critical care medicine · 2018Article
- Dietary Nutrient Intake, Ethnicity, and Epigenetic Silencing of Lung Cancer Genes Detected in Sputum in New Mexican Smokers.Cancer prevention research (Philadelphia, Pa.) · 2018Article
- Gene Methylation Biomarkers in Sputum and Plasma as Predictors for Lung Cancer Recurrence.Cancer prevention research (Philadelphia, Pa.) · 2017Article
- Article
- The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer.JCI insight · 2016Article
- Genome-wide association studies and epigenome-wide association studies go together in cancer control.Future oncology (London, England) · 2016Article
- Toxicity and Pharmacokinetic Studies of Aerosolized Clinical Grade Azacitidine.Clinical lung cancer · 2016Article
- ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic effect of ajoene on cells of lung adenocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- A prospective and retrospective analysis of smoking behavior changes in ever smokers with high risk for lung cancer from New Mexico and Pennsylvania.International journal of molecular epidemiology and genetics · 2016Article
- Epigenetic Repression of CCDC37 and MAP1B Links Chronic Obstructive Pulmonary Disease to Lung Cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 4 institutions in 1 country.
Shuguang Leng: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Yushi Liu: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Joel L Weissfeld: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Cynthia L Thomas: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Younghun Han: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Maria A Picchi: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Christopher K Edlund: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Randall P Willink: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Autumn L Gaither Davis: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Kieu C Do: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Tomoko Nukui: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Xiequn Zhang: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Elizabeth A Burki: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
David Van Den Berg: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Marjorie Romkes: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
W James Gauderman: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Richard E Crowell: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Yohannes Tesfaigzi: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Christine A Stidley: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Christopher I Amos: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Jill M Siegfried: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Frank D Gilliland: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS).
Steven A Belinsky: Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM (SL, YL, CLT, MAP, RPW, KCD, XZ, EAB, YT, SAB); Department of Epidemiology, Graduate School of Public Health (JLW) and Department of Medicine (TN, MR), University of Pittsburgh, Pittsburgh, PA; Center for Genomic Medicine, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (CKE, DVDB, WJG, FDG); Department of Pharmacology & Chemical Biology, Hillman Cancer Center of the University of Pittsburgh Medical Center, Pittsburgh, PA (ALGD, JMS); Department of Internal Medicine, University of New Mexico, Albuquerque, NM (REC, CAS); Department of Pharmacology, University of Minnesota, Minneapolis, MN (JMS). sbelinsk@LRRI.org.
Lovelace Respiratory Research Institute · USUniversity of Pittsburgh · USUniversity of Southern California · USSouthern California University for Professional Studies · US
Funding
Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3MTranslational Research Support CoreP30ES007048 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROB S MCCONNELL · 1996 to 2026
$46.4MVitamin D3 Modulation of Inflammation and Lung Cancer RiskP50CA090440 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SIEGFRIED, JILL M · 2001 to 2015
$34.6MNCI NIH HHS P30 CA023108NCI NIH HHS P50 CA090440NIEHS NIH HHS P30 ES007048
Abstract
backgroundLung 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.
methodsA genome-wide association study using generalized estimating equations and logistic regression models was conducted in two geographically independent smoker cohorts to identify loci affecting the propensity for cancer-related gene methylation that was assessed by a 12-gene panel interrogated in sputum. All statistical tests were two-sided.
resultsTwo single nucleotide polymorphisms (SNPs) at 15q12 (rs73371737 and rs7179575) that drove gene methylation were discovered and replicated with rs73371737 reaching genome-wide significance (P = 3.3×10(-8)). A haplotype carrying risk alleles from the two 15q12 SNPs conferred 57% increased risk for gene methylation (P = 2.5×10(-9)). Rs73371737 reduced GABRB3 expression in lung cells and increased risk for smoking-induced chronic mucous hypersecretion. Furthermore, subjects with variant homozygote of rs73371737 had a two-fold increase in risk for lung cancer (P = .0043). Pathway analysis identified DNA double-strand break repair by homologous recombination (DSBR-HR) as a major pathway affecting susceptibility for gene methylation that was validated by measuring chromatid breaks in lymphocytes challenged by bleomycin.
conclusionsA functional 15q12 variant was identified as a risk factor for gene methylation and lung cancer. The associations could be mediated by GABAergic signaling that drives the smoking-induced mucous cell metaplasia. Our findings also substantiate DSBR-HR as a critical pathway driving epigenetic gene silencing.
Indexed as
DNA MethylationPolymorphism, Single NucleotidePromoter Regions, GeneticSputumAdultAgedChromosomes, Human, Pair 15FemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHaplotypesHumansLogistic ModelsLung Neoplasms
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.