Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes.
OBJECTIVE
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 gamma-GCS that encode glutathione-S-transferase-pi, glutathione-S-transferase-mu, glutathione-S-transferase-theta, and gamma-glutamylcysteine synthetase, respectively. Pearson's chi(2)-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.
Yang
Ping
P
Department of Health Sciences Research, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA. yang.ping@mayo.edu
Yokomizo
Akira
A
Tazelaar
Henry D
HD
Marks
Randolph S
RS
Lesnick
Timothy G
TG
Miller
Daniel L
DL
Sloan
Jeff A
JA
Edell
Eric S
ES
Meyer
Rebecca L
RL
Jett
James
J
Liu
Wanguo
W
D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005721:Glutamate-Cysteine Ligase / Q000235:genetics* / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000401:mortality*; D008297:Male; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D012907:Smoking; D015996:Survival Rate; D013997:Time Factors
D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase