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Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage

18 Years
Open (Enrolling)
Inflammation, Cancer, Cardiomyopathy

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Trial Information

Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage

This research study will investigate the role of SNPs in p53 and p53 response elements on
the inflammatory response to DNA damage. A total of 210 healthy participants aged 18 years
and older carrying one of the seven SNPs of interest and wild-type controls will be
identified and recruited from the Environmental Polymorphism Registry (EPR). The EPR is a
long-term project to collect and store up to 15,000 DNA samples for use in research studies
from individuals in the greater North Carolina Triangle Region.

This observational gene association study will recruit participants on the basis of genotype
and then observe the phenotype of each participant. The SNPs of interest are p53, as well
as four of its downstream target genes including FLT1, MDM2, TLR8 and RRM1. A maximum of
150 mLs of blood will be obtained from each participant during one visit lasting
approximately one hour. Cells from the donated blood samples will be examined for their
response to exposed environmental stress ex vivo.

The primary objective is to determine the association between seven SNPs and p53 target gene
expression after exposure to Nutlin or doxorubicin (chemotherapeutic agents) with outcome
measured by RT-PCR. The seven SNPs are p53 rs1042522, p53 rs1800371, MDM2 rs2279744, MDM2
rs769412, FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952. The secondary objectives are to:
(1) to determine the p53 promoter occupancy measured by ChIP analysis for the following
SNPs: FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952; (2) to measure apoptosis by Annexin
V-PI assay for SNPs p53 rs1042522 and p53 rs1800371; (3) to examine the cell cycle profile
analysis (FACS) by cytofluorometry for SNPs p53 rs1042522 and p53 rs1800371; and (4) to
determine DNA repair using Pulse Field Electrophoresis Gel (TAFE gels) for the following
SNPs p53 rs1042522 and p53 rs1800371.

We hope the results of this study lead to discovery of important information regarding the
role of SNPs located in p53 and p53 response elements in human disease, potentially
identifying new targets for future studies.

Inclusion Criteria


- Male or female 18 years of age or older

- Participants must be able to understand and provide written informed consent to
participate in the study

- Participants must be able to travel to the CRU

- Healthy participants as defined by the International Red Cross guidelines (Healthy
means that an individual feels well and can perform normal activities. If the
individual has a chronic condition such as diabetes or high blood pressure, healthy
also means that they are being treated and the condition is under control).


- Use of immunosuppressants or other immune-modifying drugs [e.g., Rituxan, Humira,
Enbrel, Cyclosporin (Neoral, Sandimmune, and SangCya), Azathioprine (Imuran)],
Monoclonal antibodies [e.g., infliximab (Remicade)], Corticosteroids (e.g.,
prednisone, prednisolone and dexamethasone)

- History of being treated for cancer by chemotherapy or radiation

- Confirmed or suspected immunosuppressive or immunodeficient condition

- Body weight < 50 kg (< 110 lbs)

- Temperature > 37.6 C; blood pressure < 90/50 mm Hg or blood pressure > 170/95 mm
Hg; pulse rate < 50 or > 100 beats/minute

- Participants carrying SNPs TLR8 and FLT1 who are currently taking hormonal
contraception (e.g. oral contraceptives, IUDs with hormones, contraceptive patches)
or hormone replacement therapy will be excluded from the study unless the participant
has been off of the hormone treatment for 1 month or longer.

Type of Study:


Study Design:


Principal Investigator

Michael A Resnick, Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute of Environmental Health Sciences (NIEHS)


United States: Federal Government

Study ID:




Start Date:

May 2010

Completion Date:

Related Keywords:

  • Inflammation
  • Cancer
  • Cardiomyopathy
  • p53
  • Inflammatory Response
  • Gene Association
  • Nutlin
  • Doxorubicin
  • Healthy Volunteer
  • HV
  • Inflammation
  • Cardiomyopathies



NIEHS Clinical Research Unit (CRU) Research Triangle Park, North Carolina