About the Lab
Broad scientific aims that can be addressed through the consortium include:
Biomarkers of lung cancer risk. Extensive pilot data strongly supports the use of biomarkers in lung cancer risk prediction models. Within Project 2 we will systematically evaluate a comprehensive panel of promising risk biomarkers using pre- diagnostic blood samples. This will result in a selected panel of biomarkers of lung cancer risk that will be incorporated in risk prediction models, and used to identify those subjects most likely to benefit from CT- screening.
An integrated risk prediction model to identify individuals at high risk of lung cancer, initially analyzing epidemiological and smoking related phenotypes in the first years but then integrating targeted biomarker, genomic profile, and lung function data applied to LC CT screening populations with a total of 950 CT-detected LC patients with biosamples from 46,057 screening individuals (including 9,759 in Canada, 26,722 in NLST, and 9,576 in Europe. The clinical utility of the models will be assessed by net benefit and decision curve analysis. As a result of these analyses we will (4) develop a risk calculator for use in clinical settings. Improving personalized risk assessment for breast cancer, overall and by clinically relevant subtypes, by integrating polygenic information into risk models for risk-based prevention and screening.
A comprehensive LC probability models for individuals with LDCT-detected non-calcified pulmonary nodules. In this aim we will (a) first establish the 2Ddiameter-based probability model in N. American CT programs based on 36,481 participants, and then externally validate it based on 9,576 participants in the European LDCT programs; (b) establish the volume3D and radiomics-based probability model in European CT programs based on 9,576 participants in European CT programs, and then externally validate it in the North American CT screening populations; and (c) assess the added predictive value and clinical usefulness of targeted genomic and molecular profiles in both the 2D diameter- and 3D and radiomics volume-based LC probability models based on risk stratification table analysis and decision curve analysis. Finally we will (d) compare the model performance with the existing classification system such as Lung-RADS.
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Projects
Committees Chairs: Chris Amos and Rayjean Hung
Aim 1: Maintain and further develop a database for epidemiological, genetic and biomarker data.
Aim 2: Provide Integrative support for U19 Activities.
Aim 3: Ensure Compliance with regulatory requirements.
Aim 4: Provide Fiscal Oversight.
Committee Chair: Xihong Lin
Aim 1: Ensure rigor of biostatistical and bioinformatics approaches.
Aim 2: Provide expertise in design and analysis in statistical genetics, genomics, bioinformatics and machine learning for all projects.
Aim 3: Conduct mission related statistical methods (pathway analysis, mediation, and support mendelian randomization, also give guidance in genomics).
Aim 4: Disseminate statistical methodology via articles and web based software.
Aim 5: Provide education to students and researchers.
Committee Chairs: Paul Brennan and Mattias Johansson
Aim 1: Characterize contributions of common genetic variation to lung cancer etiology.
Aim 2: Investigate role of rare variants in lung cancer susceptibility.
Aim 3: Identify genetic effects on smoking behavior.
Aim 4: Characterize joint effects of environmental and genetic interactions on lung cancer risk.
Committee Chairs: Paul Brennan and Mattias Johansson
Aim 1: To organize the LC3, to study 2,300 former and current smoking LC cases that were diagnosed within five years of donating their blood sample along with one smoking-matched control per case.
Aim 2: To replicate a comprehensive panel of promising risk biomarkers and identify those that may be useful for risk prediction.
Aim 3: To extensively evaluate all replicated risk biomarkers from Aim 2, identifying a minimum set of validated risk biomarkers, and ultimately evaluate the extent to which they improve risk prediction models.
Committees: Rayjean Hung
Specific Aim 1: To establish an integrated risk prediction model to identify individuals at high risk of lung cancer,
Specific Aim 2: To establish a comprehensive LC probability models for individuals with LDCT-detected non-calcified pulmonary nodules.
Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk.
Ji X, Bossé Y, Landi MT, Gui J, Xiao X, Qian D, Joubert P, Lamontagne M, Li Y, Gorlov I, de Biasi M, Han Y, Gorlova O, Hung RJ, Wu X, McKay J, Zong X, Carreras-Torres R, Christiani DC, Caporaso N, Johansson M, Liu G, Bojesen SE, Le Marchand L, Albanes D, Bickeböller H, Aldrich MC, Bush WS, Tardon A, Rennert G, Chen C, Teare MD, Field JK, Kiemeney LA, Lazarus P, Haugen A, Lam S, Schabath MB, Andrew AS, Shen H, Hong YC, Yuan JM, Bertazzi PA, Pesatori AC, Ye Y, Diao N, Su L, Zhang R, Brhane Y, Leighl N, Johansen JS, Mellemgaard A, Saliba W, Haiman C, Wilkens L, Fernandez-Somoano A, Fernandez-Tardon G, van der Heijden EHFM, Kim JH, Dai J, Hu Z, Davies MPA, Marcus MW, Brunnström H, Manjer J, Melander O, Muller DC, Overvad K, Trichopoulou A, Tumino R, Doherty J, Goodman GE, Cox A, Taylor F, Woll P, Brüske I, Manz J, Muley T, Risch A, Rosenberger A, Grankvist K, Johansson M, Shepherd F, Tsao MS, Arnold SM, Haura EB, Bolca C, Holcatova I, Janout V, Kontic M, Lissowska J, Mukeria A, Ognjanovic S, Orlowski TM, Scelo G, Swiatkowska B, Zaridze D, Bakke P, Skaug V, Zienolddiny S, Duell EJ, Butler LM, Koh WP, Gao YT, Houlston R, McLaughlin J, Stevens V, Nickle DC, Obeidat M, Timens W, Zhu B, Song L, Artigas MS, Tobin MD, Wain LV, Gu F, Byun J, Kamal A, Zhu D, Tyndale RF, Wei WQ, Chanock S, Brennan P, Amos CI.
Mendelian Randomization and mediation analysis of leukocyte telomere length and risk of lung and head and neck cancers.
Kachuri L, Saarela O, Bojesen SE, Davey Smith G, Liu G, Landi MT, Caporaso NE, Christiani DC, Johansson M, Panico S, Overvad K, Trichopoulou A, Vineis P, Scelo G, Zaridze D, Wu X, Albanes D, Diergaarde B, Lagiou P, Macfarlane GJ, Aldrich MC, Tardón A, Rennert G, Olshan AF, Weissler MC, Chen C, Goodman GE, Doherty JA, Ness AR, Bickeböller H, Wichmann HE, Risch A, Field JK, Teare MD, Kiemeney LA, van der Heijden EHFM, Carroll JC, Haugen A, Zienolddiny S, Skaug V, Wünsch-Filho V, Tajara EH, Ayoub Moysés R, Daumas Nunes F, Lam S, Eluf-Neto J, Lacko M, Peters WHM, Le Marchand L, Duell EJ, Andrew AS, Franceschi S, Schabath MB, Manjer J, Arnold S, Lazarus P, Mukeriya A, Swiatkowska B, Janout V, Holcatova I, Stojsic J, Mates D, Lissowska J, Boccia S, Lesseur C, Zong X, McKay JD, Brennan P, Amos CI, Hung RJ.
Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins.
Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer, Guida F, Sun N, Bantis LE, Muller DC, Li P, Taguchi A, Dhillon D, Kundnani DL, Patel NJ, Yan Q, Byrnes G, Moons KGM, Tjønneland A, Panico S, Agnoli C, Vineis P, Palli D, Bueno-de-Mesquita B, Peeters PH, Agudo A, Huerta JM, Dorronsoro M, Barranco MR, Ardanaz E, Travis RC, Byrne KS, Boeing H, Steffen A, Kaaks R, Hüsing A, Trichopoulou A, Lagiou P, La Vecchia C, Severi G, Boutron-Ruault MC, Sandanger TM, Vainio EW, Nøst TH, Tsilidis K, Riboli E, Grankvist K, Johansson M, Goodman GE, Feng Z, Brennan P, Johansson M, Hanash SM.
Rare Variants in Known Susceptibility Loci and Their Contribution to Risk of Lung Cancer.
Liu Y, Lusk CM, Cho MH, Silverman EK, Qiao D, Zhang R, Scheurer ME, Kheradmand F, Wheeler DA, Tsavachidis S, Armstrong G, Zhu D, Wistuba II, Chow CB, Behrens C, Pikielny CW, Neslund-Dudas C, Pinney SM, Anderson M, Kupert E, Bailey-Wilson J, Gaba C, Mandal D, You M, de Andrade M, Yang P, Field JK, Liloglou T, Davies M, Lissowska J, Swiatkowska B, Zaridze D, Mukeriya A, Janout V, Holcatova I, Mates D, Milosavljevic S, Scelo G, Brennan P, McKay J, Liu G, Hung RJ; COPDGene Investigators, Christiani DC, Schwartz AG, Amos CI, Spitz MR.
Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners.
Rosenberger A, Hung RJ, Christiani DC, Caporaso NE, Liu G, Bojesen SE, Le Marchand L, Haiman CA, Albanes D, Aldrich MC, Tardon A, Fernández-Tardón G, Rennert G, Field JK, Kiemeney B, Lazarus P, Haugen A, Zienolddiny S, Lam S, Schabath MB, Andrew AS, Brunnsstöm H, Goodman GE, Doherty JA, Chen C, Teare MD, Wichmann HE, Manz J, Risch A, Muley TR, Johansson M, Brennan P, Landi MT, Amos CI, Pesch B, Johnen G, Brüning T, Bickeböller H, Gomolka M.