title: Differential roles of Angiotensinogen and Angiotensin Receptor type 1 polymorphisms in breast cancer risk.
abstract: While angiotensinogen (AGT) seems to have anti proliferative properties, angiotensin II (ATII) is a potent growth factor and it mediates its actions through the angiotensin type 1 receptor (AGTR1). In the AGT gene, the M235T polymorphism has been associated with the variation in angiotensinogen levels and in the AGTR1 gene; the C573T variant is associated with different pathologies. We aimed to evaluate the relationship of these two variants and the risk of breast cancer. These polymorphisms were genotyped in 3787 women participating the Rotterdam Study. We performed a logistic regression and a disease free survival analysis by genotype. The logistic regression yielded an odds ratio of 1.4 (95% CI: 1.1-1.9) for the MM genotype carriers versus the T allele carriers. The breast cancer free survival by AGT genotype was significantly reduced in MM genotype carriers compared to non-carriers (hazard ratio (HR) = 1.5; 95% CI: 1.1-2.2). We did not find any association of the AGTR1 polymorphism and breast cancer risk or disease free survival. Our results suggest that AGT plays a role in breast cancer risk in postmenopausal women, whereas the role of AGTR1 needs further studying.
authors.affiliation: Department of Epidemiology & Biostatistics, Erasmus University Medical Center, Postbus 1738, 3000 DR, Rotterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: González-Zuloeta Ladd
authors.forename: A
authors.initials: A
authors.lastname: Arias Vásquez
authors.forename: C
authors.initials: C
authors.lastname: Siemes
authors.forename: M
authors.initials: M
authors.lastname: Yazdanpanah
authors.forename: J W
authors.initials: JW
authors.lastname: Coebergh
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: B H Ch
authors.initials: BH
authors.lastname: Stricker
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000628:therapy; D016022:Case-Control Studies; D004247:DNA / Q000097:blood; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012307:Risk Factors
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D004247:DNA