Association of angiotensin-converting enzyme insertion/deletion polymorphism with serum level and development of pulmonary complications following esophagectomy.
BACKGROUND
Pulmonary complications remain the major cause of postoperative mortality in patients with esophageal cancer undergoing esophagectomy. It was unclear whether this dismal complication has a genetic predisposition. We therefore investigated the role of an angiotensin-converting enzyme (ACE) insertion/deletion polymorphism in developing these complications.


METHODS
We conducted a prospective study including 152 patients with esophageal cancer who underwent esophagectomy in National Taiwan University Hospital between 1996 and 2002. The ACE genotype was determined by polymerase chain reaction amplification of leukocyte DNA obtained before surgery. The serum ACE concentration was determined by enzyme-linked immunosorbent assay.


RESULTS
Thirty-five patients (23%) developed pulmonary complications following esophagectomy. As compared with patients with the I/I and I/D genotypes, those with the D/D genotype had a higher risk for pulmonary complications (adjusted odds ratio [OR], 3.12; 95% confidence interval [CI], 1.01-9.65). The risk was additively enhanced by combination of the ACE D/D genotype with other clinical risk factors (old age, hypoalbuminemia, and poor pulmonary function). The circulating ACE level was also dose-dependently with the presence of ACE D allele. As compared with the patients with circulating ACE less than 200 ng/mL, the patients with circulating ACE of 200 to 400 ng/mL and over 400 ng/mL had ORs (95% CI) of 2.75 (1.12-6.67) and 15.00 (4.3-52.34) to present with ACE D allele, respectively.


CONCLUSIONS
An ACE insertion/deletion polymorphism might modulate the function of ACE gene and play a role in affecting individual susceptibility to pulmonary injury following esophagectomy in patients of esophageal cancer.
Lee
Jang-Ming
JM
Department of Surgery, National Taiwan University Hospital, 7 Chung-Shang South Road, Taipei, Taiwan. mtuhlee@yahoo.com
Lo
An-Chi
AC
Yang
Shi-Yi
SY
Tsau
Huei-Shian
HS
Chen
Robert J
RJ
Lee
Yung-Chie
YC
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000601:surgery; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D016629:Esophagectomy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008171:Lung Diseases / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D016019:Survival Analysis
D007703:Peptidyl-Dipeptidase A