Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer.

Abstract

To date, the few studies of associations between a functional polymorphism in the oxidative stress-related gene manganese superoxide dismutase (SOD2) and breast cancer survival have been inconsistent. In a homogeneous patient population from a large cooperative group trial Southwest Oncology Group (SWOG) 8897, we evaluated this polymorphism in relation to both treatment-related toxicity and disease-free survival (DFS). Among 458 women who received cyclophosphamide-containing adjuvant chemotherapy, those with variant C alleles, related to higher antioxidant activity, experienced less grade 3-4 neutropenia (OR = 0.52, 95% CI = 0.29-0.92) but had worse DFS (HR = 1.59, 95% CI = 0.99-2.55) than women with TT genotypes. No associations were observed among 874 women who were followed without adjuvant therapy. Our results are consistent with the hypothesis that women with higher SOD2 antioxidant activity may experience less treatment-related toxicity but shorter time to disease recurrence or death after breast cancer adjuvant chemotherapy, supporting the modifying effects of oxidative stress-related enzymes on cancer treatment toxicity and efficacy.

• Authors: Song Yao, William E Barlow, Kathy S Albain, Ji-Yeob Choi, Hua Zhao, Robert B Livingston, Warren Davis, James M Rae, I-Tien Yeh, Laura F Hutchins, Peter M Ravdin, Silvana Martino, Alan P Lyss, C Kent Osborne, Martin D Abeloff, Gabriel N Hortobagyi, Daniel F Hayes, Christine B Ambrosone
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 124 Issue 2 Pg. 433-9 (Nov 2010) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 20309628 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Tamoxifen
• Doxorubicin
• Cyclophosphamide
• Superoxide Dismutase
• superoxide dismutase 2
• Fluorouracil
• Methotrexate

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, enzymology, genetics, mortality)
• Chemotherapy, Adjuvant
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Gene Frequency
• Genetic Predisposition to Disease
• Humans
• Logistic Models
• Methotrexate (administration & dosage)
• Middle Aged
• Neutropenia (chemically induced, enzymology, genetics)
• Odds Ratio
• Phenotype
• Polymorphism, Genetic
• Prospective Studies
• Risk Assessment
• Risk Factors
• Severity of Illness Index
• Southwestern United States
• Superoxide Dismutase (genetics, metabolism)
• Tamoxifen (administration & dosage)
• Time Factors
• Treatment Outcome