Peijian Ding1, Yang Yang2, Shuangjian Ding3, Baoxin Sun4. 1. The Third Department of General Surgery, the Affiliated Hospital of Chengde Medical College, China peijianding@163.com bxs19650116@163.com. 2. The Third Department of Orthopedics, the Affiliated Hospital of Chengde Medical College, China. 3. Party Committee Office, the Affiliated Hospital of Chengde Medical College, China. 4. The Third Department of General Surgery, the Affiliated Hospital of Chengde Medical College, China.
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. METHODS AND 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). CONCLUSION: 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.
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. METHODS AND 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). CONCLUSION: 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.