Related Experiment Video

Updated: May 16, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

Significance of MDM2 and P14 ARF polymorphisms in susceptibility to differentiated thyroid carcinoma

Fenghua Zhang1, Li Xu, Qingyi Wei

  • 1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Surgery
|December 11, 2012
PubMed
Abstract

Insights

Genetic variations in MDM2 and p14ARF influence differentiated thyroid carcinoma (DTC) risk. Specific polymorphisms in MDM2 and p14ARF, particularly when combined, increase DTC susceptibility, especially in younger, healthier individuals.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Differentiated thyroid carcinoma (DTC) involves mutations in the MAPK pathway.
  • Murine double minute 2 (MDM2) oncoprotein and p14ARF tumor suppressor regulate p53 and MAPK pathway activity.
  • Functional polymorphisms in MDM2 and p14ARF promoter regions may influence individual susceptibility to DTC.

Purpose of the Study:

  • To investigate the association between specific genetic polymorphisms in MDM2 and p14ARF and the risk of developing DTC.
  • To determine if combined genotypes of MDM2 and p14ARF confer a differential risk for DTC.

Main Methods:

  • Genotyping of MDM2-rs2279744, MDM2-rs937283, p14ARF-rs3731217, and p14ARF-rs3088440 in 303 DTC patients and 511 controls.
  • Multivariate logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Main Results:

  • MDM2-rs2279744 (TT genotype) and p14ARF-rs3731217 (TG/GG genotype) were significantly associated with increased DTC risk (OR=1.5 and 1.7, respectively).
  • Individuals with 3-4 risk genotypes of MDM2 and p14ARF had a 2.2-fold increased risk of DTC.
  • The combined effect was more pronounced in younger individuals (≤45 years), nonsmokers, nondrinkers, and those with a family history of cancer.

Conclusions:

  • Polymorphisms in MDM2 and p14ARF contribute to interindividual differences in DTC susceptibility, acting either independently or jointly.
  • The findings suggest a potential genetic predisposition to DTC linked to these gene variants, particularly in specific demographic subgroups.
  • Further validation in independent populations is recommended to confirm these associations.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...