Gastroenterology

Gastroenterology

Volume 131, Issue 6, December 2006, Pages 1700-1705
Gastroenterology

Clinical–alimentary tract
Microsatellite Instability in Interval Colon Cancers

https://doi.org/10.1053/j.gastro.2006.10.022Get rights and content

Background & Aims: 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.

Section snippets

Selection of Study Subjects

All veterans with a diagnosis of cancer at the Minneapolis Veterans Affairs Medical Center are entered into a cancer registry and are monitored for lifetime follow-up. The registry currently has data on 34,738 patients with cancer and has consistently achieved >95% follow-up. We searched the cancer registry from January 1, 1989, to December 31, 2004, and identified all patients with incident colon cancer. We excluded those with familial adenomatous polyposis or inflammatory bowel disease.

Results

During the specified period, 993 patients with colon cancer were identified from the Minneapolis Veterans Affairs Medical Center cancer registry and met entry criteria for the study. Of these, 51 patients developed colon cancers within 5 years of their most recent colonoscopy and were termed interval cancers. These interval cancers accounted for 5.1% of all colon cancers diagnosed at our institution. During the same period, 112 patients with noninterval colon cancer were selected (as described

Discussion

We found evidence to support that interval cancers were more likely than noninterval cancers to represent tumors with a biological propensity for rapid growth. Interval cancers had nearly 4 times the odds of demonstrating MSI when compared with noninterval cancers, an association that was strongest for tumors located in the distal colon. Interval cancers were also more likely to be located in the proximal colon and were smaller in size than noninterval cancers. Unexpectedly, we found a trend

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    Supported in part by the VA Clinical Science R&D Service (grant 04S-CRCOE-001 to M.S.S. and T.S.R.) and a grant from the Minnesota Medical Foundation (Minneapolis, MN).

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