A Study of the Interaction Between Tumor Susceptibility Gene Glycine N-methyltransferase (GNMT) and Lung Cancer

A Study of the Interaction Between Tumor Susceptibility Gene GNMT and Lung Cancer

Environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs) were reviewed as the major risk factors for lung cancer development. In this proposal, the investigators collected fifteen kinds of major PAHs and the investigators would like to perform the following studies:

1. Study the gene expression and subcellular localization of GNMT in the normal-tumor tissue pairs of lung cancer patients.
2. Study the associations of the polymorphisms of GNMT in lung cancer patients and the susceptibility to lung cancer;
3. To assess the allelic loss at GNMT and determined the LOH rate of GNMT in the normal-tumor tissue pairs of lung cancer patients.
4. Study the associations of the copy number variation (CNV) of GNMT and the susceptibility to lung cancer;
5. Study the interaction between GNMT and polycyclic aromatic hydrocarbons (PAHs) in lung cancer cell lines.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer

Detailed Description

Multi-functional protein Glycine N-methyltransferase (GNMT, EC2.1.1.20, localized to chromosome 6p12), affects genetic stability by a) regulating the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocystine (SAH) and b) binding to folate. Based on the following observations, GNMT is classified as a tumor susceptibility gene: a) diminished GNMT expression levels in both human hepatocellular carcinoma (HCC) cell lines and tissues; b) genotypic analyses of several human GNMT gene polymorphisms showed a loss of heterozygosity in 36-47% of the genetic markers in HCC tissues and also related to the susceptibility of prostate cancer; c) GNMT binds to environmental carcinogens such as benzo(a)pyrene (BaP) and aflatoxin B1 (AFB1) and protect the liver cells by inhibiting DNA-adduct formation.

Environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs) were reviewed as the major risk factors for lung cancer development. In this proposal, the investigators collected fifteen kinds of major PAHs and would like to perform the following studies:

1. Study the gene expression and subcellular localization of GNMT in the normal-tumor tissue pairs of lung cancer patients.
2. Study the associations of the polymorphisms of GNMT in lung cancer patients and the susceptibility to lung cancer;
3. To assess the allelic loss at GNMT and determined the LOH rate of GNMT in the normal-tumor tissue pairs of lung cancer patients.
4. Study the associations of the copy number variation (CNV) of GNMT and the susceptibility to lung cancer;
5. Study the interaction between GNMT and polycyclic aromatic hydrocarbons (PAHs) in lung cancer cell lines.

So far, the investigators have analyzed the gene expression of GNMT in the normal-tumor tissue pairs of some lung cancer patients. The investigators also analyzed the interaction between the GNMT and some PAHs using lung cancer cell lines. These data are helpful to clarify the susceptibility of lung cancer patients with the gene expression in GNMT.

This study is helpful in elucidating the role of GNMT plays in the tumorigenesis of lung cancer which may have important implications in the development of strategies for the prevention, diagnosis and treatment of lung cancer and other types of cancer.

• Study Type: Observational
• Enrollment (Anticipated): 200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

primary care clinic

Description

Inclusion Criteria:

• Participant is a lung cancer patient.

Exclusion Criteria:

• Participant is under 18 years old.
• Participant is not a lung cancer patient.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Collaborators and Investigators

• Sponsor: China Medical University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: October 13, 2011
• First Submitted That Met QC Criteria: October 14, 2011
• First Posted (Estimate): October 17, 2011

Study Record Updates

• Last Update Posted (Estimate): October 17, 2011
• Last Update Submitted That Met QC Criteria: October 14, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: lung cancer; tumor susceptibility gene; glycine N-methyltransferase (GNMT); polycyclic aromatic hydrocarbons (PAHs)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease Attributes; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Disease Susceptibility
• Other Study ID Numbers: DMR99-IRB-196

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No