Insertion/deletion polymorphism of angiotensin I-converting enzyme gene is linked with chromophobe renal cell carcinoma.
To study the putative significance of angiotensin I-converting enzyme (ACE) in renal cell carcinoma (RCC). Recent evidence has suggested that a 287-base pair insertion (I)/deletion (D) polymorphism (rs4646994) of the angiotensin I-converting enzyme (ACE) might be associated with cancer risk and progression. The present case-control study accrued 383 subjects, including 210 with RCC and 173 age- and sex-matched healthy individuals without evidence or a history of cancer. Genomic DNA was extracted from the peripheral blood leukocytes. The ACE fragment containing the polymorphism was amplified using conventional polymerase chain reaction using specific primer pairs and subsequently genotyped using agarose gel electrophoresis. Overall, a DD genotype and D allele were more frequently noted in the patients with RCC than in the controls (P = .042 and P = .045, respectively), and resulted from a greater frequency of DD and D in chromophobe RCC (P = .023 and P = .020, respectively). In contrast, the genotype and allele distribution of the controls and patients with papillary or clear cell RCC was similar. The II genotype was not observed in any patient with chromophobe RCC. On multivariate logistic regression analysis, the ACE genotype was an independent risk factor for chromophobe RCC (P = .012). Neither the ACE genotypes or alleles were associated with the tumor stage or grade. The results of the present study have shown for the first time that the ACE insertion/deletion gene polymorphism rs4646994 might be linked with the development of chromophobe RCC. Neither the ACE genotypes nor the alleles were associated with RCC progression.