DNA Repair, p53 and Apoptosis Phenotypes in Lung Cancer

Trial Information

DNA Repair, p53 and Apoptosis Phenotypes in Lung Cancer

The Laboratory of Human Carcinogenesis is conducting an observational lung cancer
case-control study in Baltimore, MD. This molecular epidemiology study has been specifically
developed to test the reliability and validity of the mutagen sensitivity assay, where a
case-control study is needed to assess the possibility of case bias (i.e., results vary due
to the concurrent presence of lung cancer rather than risk). Importantly, this protocol
establishes a resource that allows for the validation of these assays and also for the study
of other biomarkers and gene-environment interactions. In 2010, IRB approval was received
to include this study in a multi-institution genome-wide association study (GWAS) of lung
cancer in African Americans. The target accrual number is 4000 total subjects, consisting of
360 cases of each gender in African Americans and 640 cases for each gender in Caucasians.
An equal number of controls will be selected for each category of cases based on the
combination of gender and race. Upon recruitment, cases and controls receive a structured,
in person interview assessing prior medical and cancer history, tobacco use, alcohol use,
current medications, occupational history, family medical history, menstrual history and
estrogen use, recent nutritional supplements and caffeine intake, and socioeconomic status.
Specimen collection consists of a one-time blood sample and/or mouthwash to collect cheek
cells (oral cells) and a one-time urine sample. In addition, cancer and surrounding
non-cancer tissue that was surgically removed and not needed for diagnosis may be obtained
for cases, as well as current medical information from medical records. The phenotypic
markers to be studied will assess proficiency of DNA repair by using lymphocyte cultures
exposed in vitro to radiation, bleomycin, benzo(a)pyrene-diol-expoxide and then measuring
induction of chromosomal aberrations, p53 induction and apoptosis. DNA from buffy coats or
cheek cells will be used for analysis of genetic polymorphism in the form of Single
Nucleotide Polymorphisms (SNPs) in genes involved in DNA repair, innate immunity, cell cycle
control, angiogenesis, apoptosis, cytokines, nicotine addiction, inflammation, hormone
metabolism and microRNA. Tumors from cases will be evaluated for estrogen and progesterone
receptors. Urine, plasma and serum samples will be analyzed using an untargeted metabolomics
approach.

PRIMARY OBJECTIVES:

- To determine if mutagen sensitivity, p53 induction, and apoptosis in cultured
lymphocytes are predictive of lung cancer risk.

- To investigate and develop phenotypic or predictive markers of lung cancer risk and
survival, based on mutagen sensitivity, polymorphic markers, gene expression, and
metabolomics.

- To determine the relationship between sex-steroid metabolism, estrogen exposure, and
lung cancer risk.

ELIGIBILITY:

- Meets one of the following criteria:

- Histologically confirmed non-small cell lung cancer (case), diagnosed within the past 6
months.

- Frequency matched to cases according to age (5-year intervals), gender, and race
(population-based control).

- Resides in the state of Maryland.

- Subject Characteristics:

- Speaks English well enough to be interviewed

- Born in the United States

- Physically and mentally capable of performing the interview (i.e., must be able to hear
the interviewer, mentally comprehend the interviewers questions, and verbally respond)

- Has never been interviewed as a control for this study

- Does not currently reside in an institution such as a prison, nursing home, or shelter

- No history of cancer other than nonmelanoma skin cancer or carcinoma in situ of the
cervix (population-based control)

- Has a residential working phone within the home (population-based control)