Related Experiment Video

Updated: May 3, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.6K

Pharmacogenetics of DNA repair gene polymorphisms in non-small-cell lung carcinoma patients on platinum-based

L Zhang1, W Ma2, Y Li1

  • 1Department of General Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Genetics and Molecular Research : GMR
|January 22, 2014
PubMed

Insights

Genetic variations in XRCC1 and XPD influence non-small cell lung cancer (NSCLC) patient response to platinum chemotherapy. Specific XRCC1 polymorphisms improve outcomes, while certain XPD alleles are linked to poorer survival, aiding personalized NSCLC treatment strategies.

Area of Science:

  • Genetics
  • Oncology
  • Pharmacogenomics

Background:

  • Host-inherited factors, specifically gene polymorphisms, significantly impact individual differences in chemosensitivity and clinical outcomes for non-small cell lung carcinoma (NSCLC) patients.
  • Platinum-based chemotherapy is a cornerstone treatment for NSCLC, but patient responses vary considerably.

Purpose of the Study:

  • To investigate the impact of specific XRCC1 (Arg194Trp, Arg280His, Arg399Gln) and XPD (Arg156Arg, Asp312Asn, Asp711Asp, Lys751Gln) gene polymorphisms on the efficacy of platinum-based chemotherapy in NSCLC patients.
  • To evaluate the association between these gene polymorphisms and progression-free survival (PFS) and overall survival (OS) in NSCLC patients.

Main Methods:

  • Genotyping of XRCC1 and XPD gene polymorphisms was performed in 375 NSCLC patients undergoing platinum-based chemotherapy using duplex PCR.
  • Treatment response, progression-free survival (PFS), and overall survival (OS) were assessed.
  • Cox regression analysis was utilized to calculate adjusted hazard ratios (HR) for survival outcomes.

Main Results:

  • The XRCC1 Arg399Gln (399A/A) polymorphism was significantly associated with a better response to chemotherapy.
  • Patients with the XPD Asp711Asp and XPD Asp312Asn alleles exhibited poorer responses to chemotherapy compared to wild-type genotypes.
  • The XRCC1 399A/A polymorphism correlated with improved PFS (HR=0.61) and OS (HR=0.55).
  • Conversely, the XPD Asp711Asp allele was linked to worse PFS (HR=1.89) and OS (HR=1.90).
  • The XPD Asp312Asn allele showed a trend towards reduced survival (HR=1.73), though not statistically significant.

Conclusions:

  • Polymorphisms in the XRCC1 and XPD genes are demonstrably related to the efficacy of platinum-based chemotherapy in NSCLC patients.
  • These genetic markers can inform therapeutic decisions, paving the way for individualized treatment strategies in NSCLC management.
  • Pharmacogenetic profiling holds promise for optimizing NSCLC treatment outcomes.

More Related Videos

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays04:07

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Published on: February 24, 2023

2.5K
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer07:59

Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

1.8K

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...
81
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
159
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
138
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
94
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
194
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
121