Genetic Epidemiology of Lung Cancer and Smoking

NCT00340340 | Completed

• 2 other identifiers: 99990121101-C-N211
• Study Type: observational
• Target: 4,429
• Locations: 1 country
• Sites: 18

Brief Summary

We will conduct an interdisciplinary case-control/sib-pair study of lung cancer designed to explore the genetic determinants both of lung cancer and of smoking. The study includes biospecimen collection as well as exposure information with power to address main genetic effects and gene-environment interactions. This is an integrated proposal designed to address two major issues: the genetic determinants of lung cancer in smokers and the genetic determinants of smoking. Other important issues will be addressed in the study with a marginal additional cost to the main design. The study achieves excellent power for studying the main effects of genetic factors that are relatively common and good power for formal tests of interactive effects. Using a case-control design, with questionnaire, medical record abstraction, and blood collection, we will investigate: main effects of genes on lung cancer risk; gene-environment and gene-gene effects in lung cancer etiology; gene effects on smoking persistence; gene effects on ever-never smoking; gene-psychological interactions in smoking behaviors. In addition, we will collect viable lymphocytes from all study subjects and tumor, metaplastic and normal tissue samples from 100 surgical cases. With these data and tissues, we will be able to study: genetic instabilities in lung cancer tissue in relation to specific exposures, genotype, persistence of smoking, and clinical presentation of lung cancer; histologic characteristics of lung cancer in relation to genotype, gene expression, somatic mutations, and smoking; functional assays in viable lmphocytes in relation to genotype, gene expression. Finally, we will identify lung cancer-affected siblings of cases, and the unaffected siblings in the same sibships. This sample will permit us to: replicate associations found in the case-control sample with an alternative analytical method based on transmission statistics; address some population stratification issues.

Conditions

Lung Cancer

Keywords

Population-Based Case Control Study; Lung Cancer; Epidemiology; Smoking; Smokers; Genetics

Outcome Measures

Primary Outcomes (1)

• Tobacco smoking and other exposures and genetic susceptibility measures

  Risk of lung cancer

  Ongoing

Study Arms (2)

Cases

Newly diagnosed lung cancer cases

Controls

Population-based controls

Eligibility Criteria

• Age: 35 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Lung cancer cases consecutively enrolled from 13 hospitals and population-based controls with no cancer.

You may qualify if:

• The case group will consist of 2,000 newly incident lung cancer cases, male and female, 35 to 79 years old, with verified lung cancer, collected before or after surgery and prior to chemotherapy or radiation therapy.
• All histologic types and all stages of lung cancer will be eligible.
• Cases will be consecutively collected in the departments of thoracic surgery, general surgery, general medicine, and oncology.
• The pool of cases will be residents of Lombardy derived from 5 cities (Milan, Brescia, Varese, Monza, and Pavia) and the surrounding residential villages served by 14 hospitals, that encompass all five medical schools in the region.
• Enrolled cases will have no history of other cancers, except for basal cell carcinoma of the skin or in situ cervical carcinoma.
• Subjects in intensive care units, or with cardiac, hepatic, renal, or CNS failure, or with uncompensated schizophrenia, psychosis, or inability to speak, will not be enrolled.
• All subjects will sign an informed consent.
• The control group will consist of 2,000 gender-, age-, and county-matched controls with no history of cancer.
• We will choose a population-based or hospital-based control group depending on the result of a pilot study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (18)

Ospedale Fatebenefratelli Sant'Orsola

Brescia, Italy

Location

Spedali Civili

Brescia, Italy

Location

Azienda Ospedaliera San Paolo

Milan, Italy

Location

Euromedia Marketing Service

Milan, Italy

Location

Fondazione Centro San Raffaele - HSR

Milan, Italy

Location

Hosp Niguarda Ca Granda

Milan, Italy

Location

Istituti Clinici de Perfezionamento ICP

Milan, Italy

Location

L'Azienda Ospedaliera Fatebenefratelli e Oftalmico

Milan, Italy

Location

Ospedale Maggiore di Milano

Milan, Italy

Location

Ospedale San Carlo Borromeo

Milan, Italy

Location

Ospedale San Giuseppe

Milan, Italy

Location

Universita Degli Studi di Milano

Milan, Italy

Location

Azienda Ospedaliera Luigi Sacco

Milan, Italy

Location

Interfield

Milan, Italy

Location

Azienda Ospedaliera San Gerardo

Monza-Milano, Italy

Location

Policlinico San Matteo

Pavia, Italy

Location

Instituto Clinica Humanitas - ICH

Rozzano-Milan, Italy

Location

Azienda Ospedale di Circolo di Varese

Varese, Italy

Location

Related Publications (3)

• Zuber V, Marconett CN, Shi J, Hua X, Wheeler W, Yang C, Song L, Dale AM, Laplana M, Risch A, Witoelar A, Thompson WK, Schork AJ, Bettella F, Wang Y, Djurovic S, Zhou B, Borok Z, van der Heijden HF, de Graaf J, Swinkels D, Aben KK, McKay J, Hung RJ, Bikeboller H, Stevens VL, Albanes D, Caporaso NE, Han Y, Wei Y, Panadero MA, Mayordomo JI, Christiani DC, Kiemeney L, Andreassen OA, Houlston R, Amos CI, Chatterjee N, Laird-Offringa IA, Mills IG, Landi MT. Pleiotropic Analysis of Lung Cancer and Blood Triglycerides. J Natl Cancer Inst. 2016 Aug 26;108(12):djw167. doi: 10.1093/jnci/djw167. Print 2016 Dec.

  PMID: 27565901 BACKGROUND

• Yu G, Gail MH, Consonni D, Carugno M, Humphrys M, Pesatori AC, Caporaso NE, Goedert JJ, Ravel J, Landi MT. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome Biol. 2016 Jul 28;17(1):163. doi: 10.1186/s13059-016-1021-1.

  PMID: 27468850 BACKGROUND

• Shi J, Hua X, Zhu B, Ravichandran S, Wang M, Nguyen C, Brodie SA, Palleschi A, Alloisio M, Pariscenti G, Jones K, Zhou W, Bouk AJ, Boland J, Hicks B, Risch A, Bennett H, Luke BT, Song L, Duan J, Liu P, Kohno T, Chen Q, Meerzaman D, Marconett C, Laird-Offringa I, Mills I, Caporaso NE, Gail MH, Pesatori AC, Consonni D, Bertazzi PA, Chanock SJ, Landi MT. Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study. PLoS Med. 2016 Dec 6;13(12):e1002162. doi: 10.1371/journal.pmed.1002162. eCollection 2016 Dec.

  PMID: 27923066 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Smoking

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Behavior

Study Officials

• Maria T Landi, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2006
• First Posted: June 21, 2006
• Study Start: June 28, 2001
• Primary Completion: June 26, 2020
• Study Completion: June 26, 2020
• Last Updated: June 30, 2020

Record last verified: 2020-06

Locations

IT (18)