Genetic Epidemiology of Lung Cancer and Smoking

NCT ID: NCT00340340

Last Updated: 2020-06-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 4429 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2001-06-28
• Study Completion Date: 2020-06-26

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.

Detailed Description

This is an interdisciplinary multicenter case-control study of lung cancer situated in Milan Italy, designed to explore the genetic determinants both of lung cancer and of smoking. We enrolled newly diagnosed lung cancer cases within a defined area around Milan Italy, and population-based controls from the same area. The study includes biospecimen collection as well as epidemiological and clinical data.

This is an integrated proposal designed to address two major issues: the genetic determinants of lung cancer and the genetic determinants of smoking. Other important issues arc 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 eftects.

Using a case-control design, with questionnaire, medical record abstraction, and blood collection. we can investigate:

• main effects of genes on lung cancer risk
• gene-environment and gene-gene effects in lung cancer etiology
• gene effects on smoking persistence
• genes effects on ever-never smoking

In addition, we have collected viable lymphocytes from all study subjects and tumor, metaplastic and normal tissue samples from at least 400 surgical cases. With these data and tissues, we can 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, methylation. somatic mutations, and smoking;
• functional assays in viable lymphocytes in relation to genotype, gene expression

Moreover. we are collecting clinical reports of treatments, quality of life, recurrence, toxicities, and survival from all cases that consented. With this material we will be able to link the genetic profiles of the cases with data on therapy efficacy, toxicity and survival, to contribute to the improvement of treatment for lung cancer.

Conditions

Lung Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Cases

Newly diagnosed lung cancer cases

No interventions assigned to this group

Controls

Population-based controls

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria T Landi, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Ospedale Fatebenefratelli Sant'Orsola

Brescia, , Italy

Spedali Civili

Brescia, , Italy

Azienda Ospedaliera San Paolo

Milan, , Italy

Euromedia Marketing Service

Milan, , Italy

Fondazione Centro San Raffaele - HSR

Milan, , Italy

Hosp Niguarda Ca Granda

Milan, , Italy

Istituti Clinici de Perfezionamento ICP

Milan, , Italy

L'Azienda Ospedaliera Fatebenefratelli e Oftalmico

Milan, , Italy

Ospedale Maggiore di Milano

Milan, , Italy

Ospedale San Carlo Borromeo

Milan, , Italy

Ospedale San Giuseppe

Milan, , Italy

Universita Degli Studi di Milano

Milan, , Italy

Azienda Ospedaliera Luigi Sacco

Milan, , Italy

Interfield

Milan, , Italy

Azienda Ospedaliera San Gerardo

Monza-Milano, , Italy

Policlinico San Matteo

Pavia, , Italy

Instituto Clinica Humanitas - ICH

Rozzano-Milan, , Italy

Azienda Ospedale di Circolo di Varese

Varese, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 27565901 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27468850 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27923066 (View on PubMed)

Other Identifiers

01-C-N211

Identifier Type: -

Identifier Source: secondary_id

999901211

Identifier Type: -

Identifier Source: org_study_id