title: Synergistic association of six well-characterized polymorphisms in three genes of the renin-angiotensin system with breast cancer among Han Chinese women.
abstract: OBJECTIVE
  Breast cancer is the most common malignancy that is believed to be largely under genetic control. We therefore investigated both individual and interactive associations of six well-characterized polymorphisms in three genes of the renin-angiotensin system with breast cancer among Han Chinese women.
  
  
  RESULTS
  This was a hospital-based study involving 606 patients diagnosed with sporadic breast cancer and 633 age- and ethnicity-matched controls. There were significant differences in genotype and allele distributions of ACE gene rs4343 (pgentoype = 0.002 and pallele < 0.001) and AGTR1 gene rs5186 polymorphisms (pgentoype < 0.001 and pallele < 0.001), even with a Bonferroni-corrected alpha of 0.0042 (0.05/12). Allele combinations of T-T-T-G-C-A (alleles in order of rs5050, rs699, rs4291, rs4343, rs188018 and rs5186), G-C-T-G-C-A and T-C-T-G-C-C, respectively, had the age-adjusted odds of 2.21 (p = 0.021), 3.01 (p = 0.021) and 5.24 (p = 0.015) for breast cancer, whereas allele combination T-C-T-A-T-A was associated with a 76% (p = 0.008) reduced risk. Interaction analysis revealed an overall best two-locus model including rs4343 and rs4291 polymorphisms, and this model had the maximal testing accuracy of 0.6259 with a cross-validation consistency of 10 (p = 0.0015).
  
  
  CONCLUSIONS
  Our findings support a contributory role of the ACE gene, with its genetic polymorphisms acting synergistically, in predisposition to breast cancer among Han Chinese women.
authors: The Third Department of General Surgery, the Affiliated Hospital of Chengde Medical College, China peijianding@163.com bxs19650116@163.com.
authors: Peijian
authors: P
authors: Ding
authors: The Third Department of Orthopedics, the Affiliated Hospital of Chengde Medical College, China.
authors: Yang
authors: Y
authors: Yang
authors: Party Committee Office, the Affiliated Hospital of Chengde Medical College, China.
authors: Shuangjian
authors: S
authors: Ding
authors: The Third Department of General Surgery, the Affiliated Hospital of Chengde Medical College, China.
authors: Baoxin
authors: B
authors: Sun
mesh_terms: D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: Breast cancer; association study; gene; polymorphism; the renin-angiotensin system