title: Genetic polymorphism in the manganese superoxide dismutase gene, antioxidant intake, and breast cancer risk: results from the Shanghai Breast Cancer Study.
abstract: BACKGROUND
  It has been suggested that oxidative stress and mitochondrial DNA damage play important roles in breast cancer carcinogenesis. Manganese superoxide dismutase (MnSOD) is a major enzyme that is responsible for the detoxification of reactive oxygen species in the mitochondria. A T --> C substitution in the MnSOD gene results in a Val --> Ala change at the -9 position of the mitochondrial targeting sequence (Val-9Ala), which alters the protein secondary structure and thus affects transport of MnSOD into the mitochondria.
  
  
  METHODS
  We evaluated this genetic polymorphism in association with breast cancer risk using data from the Shanghai Breast Cancer Study, a population-based case-control study conducted in urban Shanghai from 1996 to 1998. The MnSOD Val-9Ala polymorphism was examined in 1125 breast cancer cases and 1197 age-frequency-matched control individual.
  
  
  RESULTS
  Breast cancer risk was slightly elevated in women with Ala/Ala genotype (odds ratio [OR] 1.3, 95% confidence interval [CI] 0.7-2.3), particularly among premenopausal women (OR 1.8, 95% CI 0.9-3.7), as compared with those with Val/Val genotype. The increased risk with the Ala/Ala genotype was stronger among premenopausal women with a higher body mass index (OR 2.5, 95% CI 0.9-7.0) and more years of menstruation (OR 2.6, 95% CI 0.8-8.0). The risk among premenopausal women was further increased twofold to threefold among those with a low intake of fruits, vegetables, vitamin supplements, selenium, or antioxidant vitamins, including carotenes and vitamins A, C, and E. However, the frequency of the Ala allele was low (14%) in the study population, and most of the ORs provided above were not statistically significant.
  
  
  CONCLUSIONS
  The present study provides some evidence that genetic polymorphism in the MnSOD gene may be associated with increased risk of breast cancer among Chinese women with high levels of oxidative stress or low intake of antioxidants. Studies with a larger sample size are needed to confirm the findings.
authors.affiliation: Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA. qiuyin.cai@vanderbilt.edu
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Wanqing
authors.initials: W
authors.lastname: Wen
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Cheng
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000409:Alanine / Q000235:genetics; D000483:Alleles; D000975:Antioxidants / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D003043:Cocarcinogenesis; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D013482:Superoxide Dismutase / Q000235:genetics*; D014633:Valine / Q000235:genetics
chemical_list: D000975:Antioxidants; D013482:Superoxide Dismutase; D014633:Valine; D000409:Alanine