Endometrial carcinoma is one of the most common gynecological malignancies. Most cases are diagnosed in older patients with diabetes, hypertension, or obesity. The renin-angiotensin system (RAS) has a central role controlling blood pressure and sodium homeostasis. RAS polymorphisms have been reported as genetic determinants of essential hypertension. The objective of this study was to analyze angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. The presence of an angiotensin converting enzyme (ACE) polymorphism was analyzed by polymerase chain reaction in DNA isolated from peripheral blood samples of 171 women: 70 cases with endometrial cancer (age, 63.6 +/- 9.5 years) and 101 normal control women (age, 61.3 +/- 6.4 years). We detected DD genotype in 47.5%, ID genotype in 44.3%, and II genotype in 8.2% of cases. The allele frequency was 0.69 for D allele and 0.30 for I allele. In normotensives, we found that the presence of I allele (genotypes ID and II) is significantly associated to an earlier age (56.0 +/- 10.1 versus 65.8 +/- 9.9) of onset of endometrial carcinoma (P=0.029). We observed that normotensive women carriers of an allele I have a higher risk of development of endometrial cancer under the age of 63 years (odds ratio=3.60, 95% confidence interval=1.03-12.56; P=0.037). Our findings suggest that ACE polymorphism may be associated with the development of endometrial carcinoma and with the onset of this tumor in younger women. The definition of a pharmacogenomic profile of human neoplasia may help to identify targets for the development of therapeutic or chemoprevention strategies.