Manganese superoxide dismutase and breast cancer recurrence: a Danish clinical registry-based case-control study, and a meta-analysis.
BACKGROUND
Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses.


METHODS
We conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non-metastatic breast cancer from 1990-2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95% confidence intervals (95% CI) of BCR. We used random-effects meta-analytic models to evaluate the association of SOD2 polymorphisms and BCR.


RESULTS
The frequency of the SOD2-Ala allele was 70% in cases versus 71% in controls; 40% versus 44% were heterozygotes, and 30% versus 25% were homozygotes, respectively. Heterozygote and homozygote carriers of the Ala allele had no increased rate of BCR (OR = 1.1, 95%CI = 0.65, 2.0, and OR = 0.87, 95%CI = 0.47, 1.6, respectively). Five studies informed the meta-analytic models; summary estimates associating BCR for homozygote, or any inheritance of the variant Ala allele were 1.18 (95%CI = 0.74, 1.88), and 1.18, (95%CI = 0.91, 1.54), respectively.


CONCLUSIONS
Our findings do not suggest that MnSOD enzymatic activity, as measured by SOD2 genotype, affects rates of BCR among patients treated with Cyclo.
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
Deirdre P
DP
Cronin-Fenton
Institute of Pathology, Aarhus University, Aarhus, Denmark.
Mariann
M
Christensen
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark ; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
Timothy L
TL
Lash
Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
Thomas P
TP
Ahern
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
Lars
L
Pedersen
Danish Breast Cancer Cooperative Group, Copenhagen, Denmark ; Department of Breast Surgery, Aalborg University Hospital, Aalborg, Denmark.
Jens Peter
JP
Garne
Danish Breast Cancer Cooperative Group, Copenhagen, Denmark ; Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Marianne
M
Ewertz
Institute of Public Health, Aarhus University, Aarhus, Denmark.
Herman
H
Autrup
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
Henrik T
HT
Sørensen
Institute of Pathology, Aarhus University, Aarhus, Denmark.
Stephen
S
Hamilton-Dutoit
D000483:Alleles; D019943:Amino Acid Substitution; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003718:Denmark; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020125:Mutation, Missense; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012042:Registries; D012189:Retrospective Studies; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2