Microsatellite instability in interval colon cancers.
OBJECTIVE
Colon cancers that develop after a complete colonoscopy may be the result of "failure of colonoscopy" or rapid tumor growth. Tumors that develop via the mismatch repair gene pathway demonstrate rapid tumor growth. The aim of this study was to determine if interval colon cancers were more likely than noninterval cancers to result from the loss of function of mismatch repair genes and hence demonstrate microsatellite instability (MSI).


METHODS
We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with noninterval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for MSI.


RESULTS
Of the 993 colon cancers diagnosed during the study period, 51 (5.1%) were identified as an interval cancer, and 112 subjects with noninterval cancer served as a comparison group. Study subjects were almost all men. MSI was found in 30.4% of interval cancers compared with 10.3% of noninterval cancers (P = .003). After adjusting for age, interval cancers were 3.7 times more likely to show MSI than noninterval cancers (95% confidence interval, 1.5-9.1). This association was strongest for tumors located in the distal colon (odds ratio, 17.5; P = .008). No difference in TNM stage at diagnosis, histologic type or grade, or 5-year survival was found between groups.


CONCLUSIONS
Interval colon cancers were almost 4 times as likely as noninterval colon cancers to be associated with mismatch repair gene dysfunction.
Sawhney
Mandeep S
MS
Section of Gastroenterology, Minneapolis VA Medical Center, Minneapolis, Minnesota 55417, USA. sawhn001@umn.edu
Farrar
William D
WD
Gudiseva
Srivani
S
Nelson
Douglas B
DB
Lederle
Frank A
FA
Rector
Thomas S
TS
Bond
John H
JH
D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D003113:Colonoscopy; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D013997:Time Factors
D004273:DNA, Neoplasm