Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival.
BACKGROUND
Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk and survival in breast cancer. This base pair transition (-9 T > C) leads to a valine to alanine amino acid change in the mitochondrial targeting sequence. A polymorphism has also been identified in the proximal region of the promoter (-102 C>T) that alters the recognition sequence of the AP-2 transcription factor, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the -102 C>T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study.


METHODS
The relationship between the MnSOD -102 C>T polymorphism and survival was examined in a cohort of 291 women who received chemotherapy and/or radiotherapy for incident breast cancer. The MnSOD -102 C>T genotype was determined using a TaqMan allele discrimination assay. Patient survival was evaluated according to the MnSOD genotype using Kaplan-Meier survival functions. Hazard ratios were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided.


RESULTS
In an evaluation of all women, there was a borderline significant reduction in recurrence-free survival with either one or both variant alleles (CT + TT) when compared with patients with wild-type alleles (CC) (odds ratio, 0.65; 95% confidence interval, 0.42-1.01). When the analysis was restricted to patients receiving radiation therapy, there was a significant reduction in relapse-free survival in women who were heterozygous for the MnSOD -102 genotype (relative risk, 0.40; 95% confidence interval, 0.18-0.86). Similarly, when the homozygous and heterozygous variant genotypes were combined, there remained a significant reduction in relapse-free survival in this group (hazard ratio, 0.42; 95% confidence interval, 0.20-0.87).


CONCLUSIONS
The MnSOD -102 variant allele appears to be associated with an improved recurrence-free survival in all patients, and more dramatically in subjects who received adjuvant radiation therapy.
Martin
Robert C G
RC
Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA. Robert.martin@louisville.edu
Ahn
Jiyoung
J
Nowell
Susan A
SA
Hein
David W
DW
Doll
Mark A
MA
Martini
Benjamin D
BD
Ambrosone
Christine B
CB
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D016019:Survival Analysis
D013482:Superoxide Dismutase