@article{9d1730502a2f439bb3e827d2feaf9855,
title = "Clinical and Genomic Characterization of Interval Colorectal Cancer in 3 Prospective Cohorts",
abstract = "Background & Aims: Interval colorectal cancers (CRCs), cancers diagnosed after a screening/surveillance examination in which no cancer is detected, and before the date of next recommended examination, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutational characteristics of interval CRCs in comparison with screen detected CRCs. Methods: We included 1175 CRCs documented in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and 3661 CRCs in the Nurses{\textquoteright} Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Multivariable Cox models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of death risk. Whole exome sequencing was conducted in 147 PLCO cases and 796 NHS/HPFS cases. Results: A total of 619 deaths (312 CRC-specific) and 2404 deaths (1904 CRC-specific) were confirmed during follow-up of PLCO and NHS/HPFS, respectively. Compared with screen detected CRCs, interval CRCs had a multivariate-adjusted HR (95% CI) of 1.47 (1.21–1.78) for CRC-specific mortality and 1.27 (1.09–1.47) for overall mortality (meta-analysis combining all 3 cohorts). However, we did not observe significant differences in mutational features between interval and screen detected CRCs (false discovery rate adjusted P > .05). Conclusion: Interval CRCs had a significantly increased risk of death compared with screen detected CRCs that were not explained by established clinical prognostic factors, including stage at diagnosis. The survival disadvantage of interval CRCs did not appear to be explained by differences in the genomic landscape of tumors characterized by whole exome sequencing.",
keywords = "Colonoscopy, Interval Colorectal Cancer, Screening, Whole Exome Sequencing",
author = "Keming Yang and Yin Cao and Carino Gurjao and Yang Liu and Guo, {Chuan Guo} and Lo, {Chun Han} and Xiaoyu Zong and David Drew and Connor Geraghty and Elizabeth Prezioso and Matt Moore and Craig Williams and Tom Riley and Melissa Saul and Shuji Ogino and Marios Giannakis and Adam Bass and Schoen, {Robert E.} and Chan, {Andrew T.}",
note = "Funding Information: Funding This work is supported by National Institutes of Health grants UM1 CA186107, P01 CA87969, R01 CA49449, U01 CA167552, U01CA182367, R35 CA197735, and R35CA253185, and by the Project P Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Andrew T. Chan is the Stuart and Suzanne Steele MGH Research Scholar and an American Cancer Society Clinical Research Professor. Funding Information: The authors acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention{\textquoteright}s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute{\textquoteright}s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, and Wyoming. The data of this study are available on reasonable request. Further information including the procedures to obtain and access data from the Nurses{\textquoteright} Health Studies and Health Professionals Follow-up Study is described at https://www.nurseshealthstudy.org/researchers (contact email: nhsaccess@channing.harvard.edu ) and https://sites.sph.harvard.edu/hpfs/for-collaborators/ . Funding Information: Conflict of Interest Marios Giannakis received research funding from Servier and Janssen unrelated to this study. Robert E. Schoen receives research support from Freenome, Exact Sciences, and Immunovia. Andrew T. Chan received research funding from Zoe Ltd and Freenome, research and consulting funds from Pfizer Inc, consulting funds from Boehringer Ingelheim , and consulting funds from Bayer Pharma AG – all for studies unrelated to the present manuscript. The remaining authors disclose no conflicts. Publisher Copyright: {\textcopyright} 2022 AGA Institute",
year = "2022",
month = dec,
doi = "10.1053/j.gastro.2022.08.020",
language = "English",
volume = "163",
pages = "1522--1530.e5",
journal = "Gastroenterology",
issn = "0016-5085",
number = "6",
}