Genetic determinants of lung cancer short-term survival

The role of glutathione-related genes

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

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)221-229
Number of pages9
JournalLung Cancer
Volume35
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Glutathione
Lung Neoplasms
Survival
Genes
Glutathione Transferase
Genotype
Survival Rate
Platinum Compounds
Glutamate-Cysteine Ligase
Kaplan-Meier Estimate
Enzymes
Proportional Hazards Models
Tobacco Products
Neoplasms
Therapeutics
Smoking
DNA
Pharmaceutical Preparations

Keywords

  • Chemotherapeutic
  • Glutathoine
  • Metabolism

ASJC Scopus subject areas

  • Oncology

Cite this

Genetic determinants of lung cancer short-term survival : The role of glutathione-related genes. / Yang, Ping; Yokomizo, Akira; Tazelaar, Henry D.; Marks, Randolph Stuart; Lesnick, Timothy G.; Miller, Daniel L.; Sloan, Jeff A; Edell, Eric; Meyer, Rebecca L.; Jett, James; Liu, Wanguo.

In: Lung Cancer, Vol. 35, No. 3, 2002, p. 221-229.

Research output: Contribution to journalArticle

Yang, Ping ; Yokomizo, Akira ; Tazelaar, Henry D. ; Marks, Randolph Stuart ; Lesnick, Timothy G. ; Miller, Daniel L. ; Sloan, Jeff A ; Edell, Eric ; Meyer, Rebecca L. ; Jett, James ; Liu, Wanguo. / Genetic determinants of lung cancer short-term survival : The role of glutathione-related genes. In: Lung Cancer. 2002 ; Vol. 35, No. 3. pp. 221-229.
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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.",
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T1 - Genetic determinants of lung cancer short-term survival

T2 - The role of glutathione-related genes

AU - Yang, Ping

AU - Yokomizo, Akira

AU - Tazelaar, Henry D.

AU - Marks, Randolph Stuart

AU - Lesnick, Timothy G.

AU - Miller, Daniel L.

AU - Sloan, Jeff A

AU - Edell, Eric

AU - Meyer, Rebecca L.

AU - Jett, James

AU - Liu, Wanguo

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

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KW - Metabolism

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