Association between survival after treatment for breast cancer and glutathione S-transferase P1 Ile105Val polymorphism.
A glutathione S-transferase (GST) P1 polymorphism results in an amino acid substitution, Ile105Val; the Val-containing enzyme has reduced activity toward alkylating agents. Cancer patients with the variant enzyme may differ in removal of treatment agents and in outcomes of therapy. We evaluated survival according to GSTP1 genotype among women (n = 240) treated for breast cancer. Women with the low-activity Val/Val genotype had better survival. Compared with Ile/Ile, hazard ratios for overall survival were 0.8 (95% confidence interval, 0.5-1.3) for Ile/Val and 0.3 (95% confidence interval, 0.1-1.0) for Val/Val (P for trend = 0.04). Inherited metabolic variability may influence treatment outcomes.
Sweeney
C
C
National Center for Toxicological Research, Jefferson, Arkansas 72079, USA. sweeneycarol@exchange.uams.edu
McClure
G Y
GY
Fares
M Y
MY
Stone
A
A
Coles
B F
BF
Thompson
P A
PA
Korourian
S
S
Hutchins
L F
LF
Kadlubar
F F
FF
Ambrosone
C B
CB
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D007532:Isoleucine / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000502:physiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014633:Valine / Q000235:genetics
D007527:Isoenzymes; D011960:Receptors, Estrogen; D007532:Isoleucine; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D014633:Valine