a subgroup of breast cancer patients in whom radiation therapy makes a big difference

[Lani]

AND WHY!

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Association between Manganese Superoxide Dismutase Promoter Gene
Polymorphism and Breast Cancer Survival.
Breast Cancer Research 2006, 8:R45 doi:10.1186/bcr1532
Robert CG Martin MD (Robert.martin@louisville.edu)
Jiyoung Ahn PhD (ahnj@mail.nih.gov)
Susan A Nowell PhD (SusanNowell@msn.com)
David W Hein PhD (d.hein@louisville.edu)
Mark A Doll (Mark.Doll@louisville.edu)
Ben D Martini (Ben.Martini@louisville.edu)
Christine B Ambrosone PhD (Christine.Ambrosone@RoswellPark.org)
ISSN 1465-5411
Article type Research article
Submission date 20 April 2006
Acceptance date 11 July 2006
Publication date 19 July 2006
Article URL http://breast-cancer-research.com/content/8/4/R45
This peer-reviewed article was published immediately upon acceptance. It can be downloaded,
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Breast Cancer Research
© 2006 Martin et al., licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Martin et al -

1
1
Association between Manganese Superoxide Dismutase Promoter Gene Polymorphism and
Breast Cancer Survival

Robert C.G. Martin, MD1, Jiyoung Ahn, PhD2,5, Susan A. Nowell, PhD3, David W. Hein PhD4,
Mark A. Doll4, Benjamin D. Martini4, Christine B. Ambrosone PhD5

Departments of Surgery, 1Division of Surgical Oncology, 4Pharmacology and Toxicology, and
the James Graham Brown Cancer Center, University of Louisville School of Medicine,
Louisville, Ky
2
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National
Cancer Institute, NIH, DHHS, Bethesda, MD
Division of 3Molecular Epidemiology, National Center for Toxicological Research, Jefferson,
Arkansas
Department of 5Epidemiology, Roswell Park Cancer Institute, Buffalo New York












Martin et al -
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ABSTRACT:
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.
Materials and Methods: The relationship between 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 to patients with wild type
alleles (CC) (OR 0.65, (95% CI 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 MnSOD-102 genotype (RR 0.40 95% CI 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 (HR 0.42 95% CI 0.20-0.87).
Conclusion: 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.