Manganese superoxide dismutase Ala-9Val polymorphism and risk of breast cancer in a population-based case-control study of African Americans and whites.
BACKGROUND
A polymorphism in the manganese superoxide dismutase (MnSOD) gene, Ala-9Val, has been examined in association with breast cancer risk in several epidemiologic studies. Results suggest that the Ala allele increases the risk of breast cancer and modifies the effects of environmental exposures that produce oxidative damage to DNA.


METHODS
We examined the role of the MnSOD Ala-9Val polymorphism in a population-based case-control study of invasive and in situ breast cancer in North Carolina. Genotypes were evaluated for 2025 cases (760 African Americans and 1265 whites) and for 1812 controls (677 African Americans and 1135 whites).


RESULTS
The odds ratio for MnSOD Ala/Ala versus any MnSOD Val genotypes was not elevated in African Americans (odds ratio = 0.9, 95% confidence interval = 0.7-1.2) or in whites (odds ratio = 1.0, 95% confidence interval = 0.8-1.2). Greater than additive joint effects were observed for the Ala/Ala genotype and smoking, radiation to the chest, and occupational exposure to ionizing radiation. Antagonism was observed between the Ala/Ala genotype and the use of nonsteroidal anti-inflammatory drugs.


CONCLUSIONS
The MnSOD genotype may contribute to an increased risk of breast cancer in the presence of specific environmental exposures. These results provide further evidence for the importance of reactive oxygen species and of oxidative DNA damage in the etiology of breast cancer.
Millikan
Robert C
RC
Department of Epidemiology, School of Public Health, and Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. bob_millikan@unc.edu
Player
Jon
J
de Cotret
Allan René
AR
Moorman
Patricia
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Pittman
Gary
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Vannappagari
Vani
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Tse
Chiu-Kit J
CK
Keku
Temitope
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D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000409:Alanine / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D017720:Molecular Epidemiology / Q000379:methods / Q000706:statistics & numerical data; D009657:North Carolina; D011110:Polymorphism, Genetic / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods*; D013482:Superoxide Dismutase / Q000235:genetics*; D014633:Valine / Q000235:genetics*; D044465:White People / Q000235:genetics*
D013482:Superoxide Dismutase; D014633:Valine; D000409:Alanine