Related Experiment Video

Updated: Jul 1, 2026

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
06:08

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma

Published on: June 2, 2023

Association between polymorphisms in DNA base excision repair genes XRCC1, APE1, and ADPRT and differentiated thyroid

Feng-Yu Chiang1, Che-Wei Wu, Pi-Jung Hsiao

  • 1Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|September 10, 2008
PubMed
Abstract

Insights

Specific DNA repair gene variants, particularly in XRCC1, increase the risk of developing and progressing papillary thyroid cancer (DTC). These genetic markers, especially when combined with ADPRT variants, significantly elevate susceptibility to DTC and lymph node metastasis.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • The DNA base excision repair (BER) pathway is crucial for maintaining genomic stability and is implicated in carcinogenesis.
  • Polymorphisms in BER genes may influence an individual's susceptibility to cancer development and progression.

Purpose of the Study:

  • To investigate the association between functional polymorphisms in three key BER genes (XRCC1, APE1, and ADPRT) and the risk of papillary thyroid cancer (DTC) and its progression in a Chinese population.
  • To identify specific genetic variants that contribute to DTC development and lymph node metastasis.

Main Methods:

  • Genotyping of five common nonsynonymous single nucleotide polymorphisms (SNPs) in XRCC1, APE1, and ADPRT genes.
  • Case-control study design involving Chinese DTC patients and healthy controls.
  • Statistical analysis including odds ratios, confidence intervals, and haplotype analysis to assess genetic associations and interactions.

Main Results:

  • The XRCC1-194Trp/Trp genotype was significantly associated with an increased risk of DTC (OR=1.85, P=0.018).
  • This association was primarily driven by patients with lymph node (LN) metastasis (OR=4.54, P=0.0001).
  • Combined analysis revealed that XRCC1-194Trp and ADPRT-762Ala variants synergistically increased the risk of DTC (OR=3.18, P=0.046) and particularly DTC with LN metastasis (OR=9.25, P=0.004).

Conclusions:

  • XRCC1 gene polymorphisms, specifically the 194Trp allele, play a role in the development and progression of DTC.
  • The interaction between XRCC1-194Trp and ADPRT-762Ala variants significantly enhances susceptibility to DTC and regional lymph node metastasis.
  • Identification of these genetic risk factors offers insights into DTC pathogenesis and potential strategies for prevention and treatment.

More Related Videos

Spontaneous Murine Model of Anaplastic Thyroid Cancer05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

Related Concept Videos

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...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
Graves' Disease I: Introduction01:28

Graves' Disease I: Introduction

Graves' disease is an autoimmune disorder that causes hyperthyroidism, or overactivity of the thyroid gland. It results from autoantibodies called thyroid-stimulating immunoglobulins (TSIs), which bind to thyroid-stimulating hormone (TSH) receptors, leading to overstimulation of hormone production and a hypermetabolic state.EtiologyAlthough considered idiopathic, Graves’ disease has well-established contributing factors. There is a strong genetic component, with increased prevalence in...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Base Excision Repair01:54

Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...