Genetic determinants of lung cancer short-term survival: The role of glutathione-related genes

Ping Yang, Akira Yokomizo, Henry D. Tazelaar, Randolph S. Marks, Timothy G. Lesnick, Daniel L. Miller, Jeff A. Sloan, Eric S. Edell, Rebecca L. Meyer, James Jett, Wanguo Liu

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Purpose: Survival of lung cancer patients has been dismal. Glutathione enzymes are directly involved in the metabolism of platinum compounds, a group of important chemotherapeutic drugs in cancer treatment. We tested the hypothesis that genes encoding glutathione enzymes may predict lung cancer short-term survival. Methods: We studied DNA polymorphisms of 250 primary lung cancer patients at four glutathione-related loci: GSTP1, GSTM1, GSTT1 and γ-GCS that encode glutathione-S-transferase-π, glutathione-S-transferase-μ, glutathione-S-transferase-θ, and γ-glutamylcysteine synthetase, respectively. Pearson's χ2-square tests, Kaplan-Meier survival curves, log rank tests, and Cox regression models were applied in the analysis. Results: There were 150 (60%) men and 100 (40%) women in this study. Seventeen percent of the patients had never smoked cigarettes, and 61% had stopped smoking at least 6 months prior to their lung cancer diagnosis. Among never smokers, those with null (N) or low (L) genotype experienced a better 1-year-survival rate than those with a positive (P) or high (H) genotype. Patients with P or H at two loci (PP or PH) were compared with patients with N or L at one or both loci (other). Among never smokers, 1-year-survival rates were 60-78% for patients with PP or PH genotypes compared with 89-100% for other types. The survival advantage was greater among advanced-stage patients who were NL or NN than low-stage patients. Similar results were not observed among smokers. Conclusions: Glutathione-related genes may determine lung cancer survival. Our results, if confirmed, would suggest new directions to enhance cancer treatment, and provide easily measurable markers for clinicians to plan patient-specific therapy.

Original languageEnglish
Pages (from-to)221-229
Number of pages9
JournalLung Cancer
Volume35
Issue number3
DOIs
Publication statusPublished - Feb 28 2002

All Science Journal Classification (ASJC) codes

  • Oncology

Fingerprint Dive into the research topics of 'Genetic determinants of lung cancer short-term survival: The role of glutathione-related genes'. Together they form a unique fingerprint.

Cite this