Angiotensin-converting enzyme gene insertion/deletion polymorphism and breast cancer risk.
BACKGROUND
The renin-angiotensin system plays an important role in homeostasis and lately, its main effector, angiotensin II, has been attributed with angiogenic and growth factor actions in the breast tissue. Previous studies have shown that the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene accounts for the variability of ACE plasma concentrations. The use of ACE inhibitors and the ACE I/D polymorphism may be linked to breast cancer risk. In this study, we evaluate the relationship of the ACE I/D polymorphism with breast cancer risk in Caucasian postmenopausal women.


METHODS
The ACE I/D polymorphism was genotyped in 4,117 women participants in the Rotterdam Study. Baseline information was obtained through a questionnaire. We conducted a logistic regression and survival analysis to assess the risk of breast cancer by the ACE genotype.


RESULTS
The DD carriers showed a significantly increased risk of developing breast cancer when compared with the II carriers (odds ratio, 1.86; 95% confidence interval, 1.06-3.27; P = 0.03). This association remained after adjusting for other risk factors, including body mass index, age at menarche, age at menopause, hormone replacement therapy, and hypertension. Our survival analysis showed that the cancer-free survival was significantly reduced in DD compared with II carriers (hazard ratio, 1.80; 95% confidence interval, 1.07-3.01; P = 0.03).


CONCLUSIONS
Our results suggest that the ACE I/D polymorphism plays an important role in breast cancer risk and disease-free survival in Caucasian postmenopausal women.
González-Zuloeta Ladd
Angela M
AM
Epidemiology and Biostatistics Department, Erasmus Medical Center, Rotterdam, the Netherlands.
Arias Vásquez
Alejandro
A
Sayed-Tabatabaei
Fakhredin A
FA
Coebergh
J W
JW
Hofman
Albert
A
Njajou
Omer
O
Stricker
Bruno
B
van Duijn
Cornelia
C
D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011379:Prognosis; D012083:Renin / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D016019:Survival Analysis
D012083:Renin