Stool DNA and Occult Blood Testing for Screen Detection of Colorectal Neoplasia

Abstract

Background Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting. Objective To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm). Design Blinded, multicenter, cross-sectional study. Setting Communities surrounding 22 participating academic and regional health care systems in the United States. Participants 4482 average-risk adults. Measurements Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy. Results Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030). Limitations Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers. Conclusion Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.

Advances in epigenetic biomarker research in colorectal cancer

“…Since then, many studies have been devoted to vimentin methylation. Follow-up studies have obtained similar results and thus have reinforced the utility of vimentin as a standalone biomarker [47,54,55,59,61] . This has led to the commercialization of a single-gene stool kit for CRC detection based on vimentin methylation.…”

Effect of Verification Bias on the Sensitivity of Fecal Occult Blood Testing: a Meta-Analysis

“…The studies that attempted to reduce verification bias are listed in Table 2. [51][52][53][54][55][56][57][58][59][60] These 10 studies included 185 subjects with colorectal cancer and 31,804 controls. Seven studies reduced verification bias by performing colonoscopy on all of the potential subjects 51,54-56,58-60 while 3 studies used longitudinal follow-up for at least 2 years.…”

A case‐control study of colorectal cancer detection by quantification of DNA isolated from directly collected exfoliated colonocytes

“…9,[11][12][13][14][15][16][17][18] The reliability of DNA amplification shown by our QRTPCR assay indicates that DNA isolated from material obtained with the new collection technique is of much higher quality than widely used DNA extracted from stool.…”

“…Purification of human DNA from stool is difficult, [14][15][16] and there is no unique molecular signature reliably indicating cancer presence. The latter difficulty resulted in the use of multimarker assays, 3,9,[11][12][13][14][15][16][17][18] making the cost-effectiveness of the approach a major issue. 9,[19][20][21] It has been suggested that exfoliated colonocytes collected directly from the surface of colonic mucosa could serve for diagnostic and research applications better than stool-derived material.…”

“…3,7 In many countries FOBT remains the most popular mass screening method due to its low cost, noninvasiveness and simplicity, however this test often produces both false-negative and false-positive results. [3][4][5][6][8][9][10] Stool DNA analysis targeting molecular markers in exfoliated colonocytes excreted with faeces is being actively developed, [12][13][14][15][16][17][18] but its suitability for CRC screening is still questioned. Purification of human DNA from stool is difficult, [14][15][16] and there is no unique molecular signature reliably indicating cancer presence.…”