Chronic colitis is associated with a reduction of mucosal alkaline sphingomyelinase activity.
OBJECTIVE
The hydrolysis of sphingomyelin (SM) generates key molecules regulating cell growth. Animal cancer studies support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. The activity of a specific intestinal alkaline sphingomyelinase (SMase), which hydrolyzes SM, is reduced in colorectal tumors. In this study we measured alkaline SMase activity in patients with longstanding colitis and assessed if a reduction can be used as a marker in surveillance of high risk patients.


METHODS
Alkaline SMase activity was measured in 139 colonic biopsies from 34 patients with longstanding, extensive colitis and from 11 controls. Fifteen patients had earlier diagnosis of dysplasia or DNA aneuploidy. Alkaline SMase activity was related to histologic dysplasia and DNA aneuploidy assessed by flow cytometry, patient age, and duration of disease.


RESULTS
Alkaline SMase activity was significantly lower in the patient group with and without dysplasia compared with controls (p = 0.006). In biopsies, an association was not found between alkaline SMase activity, dysplasia, or DNA ploidy. However, alkaline SMase activity decreased with age both in patients and controls (p = 0.008).


CONCLUSIONS
Reduction of alkaline SMase activity seen in colorectal cancer and adenomas is also present in patients with chronic colitis. It is not complementary to dysplasia or DNA-aneuploidy in the identification of high risk patients. The age-associated decrease of alkaline SMase activity seems to be a general phenomenon indicating premature senescence of the mucosa in longstanding colitis.
Division of Gastroenterology, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. urban.sjoqvist@sos.sll.se
Urban
U
Sjöqvist
Erik
E
Hertervig
Ake
A
Nilsson
Rui-Dong
RD
Duan
Ake
A
Ost
Bernhard
B
Tribukait
Robert
R
Löfberg
D000236:Adenoma / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000473:pathology*; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011003:Ploidies; D013108:Sphingomyelin Phosphodiesterase / Q000032:analysis* / Q000494:pharmacology
D015415:Biomarkers; D013108:Sphingomyelin Phosphodiesterase