The primary goal of Project 1 Is to characterize remediable failures of fecal immunochemical tests (FIT) to detect colorectal neoplasms, with the aim of optimizing FIT's effectiveness for community-based screening. FIT is recommended by all current national colorectal cancer (CRC) screening recommendations for screening persons at average risk for CRC. Potential advantages of FIT include that it is non-invasive, has greater sensitivity than older fecal blood tests, does not require a bowel preparation, does not require restrictions of diet or medications, has no direct associated risks, and can be used in mailed outreach programs;however, FIT may sometimes result in false negative and false positive test results. Kaiser Permanente in Northern and Southern California (KPNC/KPSC) has utilized FIT extensively to reach unscreened members;this multi-modality strategy increased screening rates among the KPNC/KPSC screening-eligible populations of >2 million members to 75%, In the top quartile of all US health plans. Despite widespread use, FIT's performance characteristics for population screening are not well characterized. A single FIT evaluation has a CRC sensitivity of 65%-80%;the effects of repeated screening have been modeled, but not reported from """"""""real life"""""""" populations. In addition, FIT performance characteristics may vary among patients, by use of anticoagulants and non-steroidal anti-inflammatory medications (which may increase tumor blood loss) and by temperature and weather conditions. In addition, DNA methylation increases as people age and this may accelerate the transformation of adenomas to carcinoma, decreasing the likelihood of detecting pre-invasive CRCs through screening. Finally, even with 100% adherence, FIT will fail to detect some cancers, although reasons for these failures have not been thoroughly explored. The current study proposes to use the large, diverse patient populations and electronic record systems of KPNC/KPSC to characterize patterns of FIT use and predictors of FIT failures, including: failures to screen, failures to detect (false negative) and failures to follow-up a positive FIT. Candidate predictors include age, sex, race/ethnicity, socioeconomic status and medical history, as well as environmental factors. A candidate next generation stool DNA test will Include a set of biomarkers (e.g. methylated vimentin, other methylation markers and k-ras) which are promising options for stool-based CRC screening. We will therefore measure these biomarkers among FIT negative vs. FIT positive cancers, to assess the potential magnitude by which a methylation marker panel might increase the detection of CRC beyond that detected by FIT alone.
Non-invasive screening with the FIT offers an important means of early detection of CRC and adenomas and is suitable for mass population screening. Understanding the magnitude and predictors of false negative FIT results, and examining alternative molecular markers for CRC detection are Important steps toward optimizing non-invasive CRC screening.
|Klabunde, Carrie N; Zheng, Yingye; Quinn, Virginia P et al. (2016) Influence of Age and Comorbidity on Colorectal Cancer Screening in the Elderly. Am J Prev Med 51:e67-75|
|Chubak, Jessica; Garcia, Michael P; Burnett-Hartman, Andrea N et al. (2016) Time to Colonoscopy after Positive Fecal Blood Test in Four U.S. Health Care Systems. Cancer Epidemiol Biomarkers Prev 25:344-50|
|Burnett-Hartman, Andrea N; Mehta, Shivan J; Zheng, Yingye et al. (2016) Racial/Ethnic Disparities in Colorectal Cancer Screening Across Healthcare Systems. Am J Prev Med 51:e107-15|
|McCarthy, Anne Marie; Kim, Jane J; Beaber, Elisabeth F et al. (2016) Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity. Am J Prev Med 51:507-12|
|Jensen, Christopher D; Corley, Douglas A; Quinn, Virginia P et al. (2016) Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening: A Retrospective Cohort Study. Ann Intern Med 164:456-63|
|Lee, Jeffrey K; Corley, Douglas A (2016) What makes a ""good"" colonoscopy quality indicator? Gastrointest Endosc 83:179-81|
|Lee, Alexander; Jensen, Christopher D; Marks, Amy R et al. (2016) Endoscopist Fatigue Estimates and Colonoscopic Adenoma Detection in a Large Community-Based Setting. Gastrointest Endosc :|
|Kim, Jane J; Tosteson, Anna Na; Zauber, Ann G et al. (2016) Cancer Models and Real-world Data: Better Together. J Natl Cancer Inst 108:|
|Tosteson, Anna N A; Beaber, Elisabeth F; Tiro, Jasmin et al. (2016) Variation in Screening Abnormality Rates and Follow-Up of Breast, Cervical and Colorectal Cancer Screening within the PROSPR Consortium. J Gen Intern Med 31:372-9|
|Meester, Reinier G S; Zauber, Ann G; Doubeni, Chyke A et al. (2016) Consequences of Increasing Time to Colonoscopy ExaminationÂ After Positive Result From Fecal Colorectal CancerÂ Screening Test. Clin Gastroenterol Hepatol 14:1445-1451.e8|
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