A Comprehensive Comparison of Early-Onset and Average-Onset Colorectal Cancers
Author:
Cercek Andrea1ORCID, Chatila Walid K234, Yaeger Rona1ORCID, Walch Henry2, Fernandes Gustavo Dos Santos1, Krishnan Asha1, Palmaira Lerie5, Maio Anna1, Kemel Yelena6ORCID, Srinivasan Preethi2, Bandlamudi Chaitanya2, Salo-Mullen Erin1, Tejada Prince R1, Belanfanti Kimeisha1, Galle Jesse1, Joseph Vijai1ORCID, Segal Neil1, Varghese Anna1, Reidy-Lagunes Diane1ORCID, Shia Jinru7ORCID, Vakiani Efsevia7, Mondaca Sebastian1, Mendelsohn Robin1, Lumish Melissa A1, Steinruecke Felix1ORCID, Kemeny Nancy1, Connell Louise1, Ganesh Karuna1, Markowitz Arnold1, Nash Garrett5, Guillem Jose5, Smith J Joshua5, Paty Phillip B5, Zhang Liying7, Mandelker Diana7ORCID, Birsoy Ozge7, Robson Mark1ORCID, Offit Kenneth1, Taylor Barry28, Berger Michael2, Solit David2, Weiser Martin5, Saltz Leonard B1ORCID, Aguilar Julio Garcia5, Schultz Nikolaus238, Diaz Luis A1, Stadler Zsofia K1
Affiliation:
1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA 2. Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 3. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA 4. Tri-Institutional Program in Computational Biology and Medicine, Weill Cornell Medical College, New York, NY, USA 5. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA 6. Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA 7. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 8. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Abstract
Abstract
Background
The causative factors for the recent increase in early-onset colorectal cancer (EO-CRC) incidence are unknown. We sought to determine if early-onset disease is clinically or genomically distinct from average-onset colorectal cancer (AO-CRC).
Methods
Clinical, histopathologic, and genomic characteristics of EO-CRC patients (2014-2019), divided into age 35 years and younger and 36-49 years at diagnosis, were compared with AO-CRC (50 years and older). Patients with mismatch repair deficient tumors, CRC-related hereditary syndromes, and inflammatory bowel disease were excluded from all but the germline analysis. All statistical tests were 2-sided.
Results
In total, 759 patients with EO-CRC (35 years, n = 151; 36-49 years, n = 608) and AO-CRC (n = 687) were included. Left-sided tumors (35 years and younger = 80.8%; 36-49 years = 83.7%; AO = 63.9%; P < .001 for both comparisons), rectal bleeding (35 years and younger = 41.1%; 36-49 years = 41.0%; AO = 25.9%; P = .001 and P < .001, respectively), and abdominal pain (35 years and younger = 37.1%; 36-49 years = 34.0%; AO = 26.8%; P = .01 and P = .005, respectively) were more common in EO-CRC. Among microsatellite stable tumors, we found no differences in histopathologic tumor characteristics. Initially, differences in TP53 and Receptor Tyrosine Kinase signaling pathway (RTK-RAS)alterations were noted by age. However, on multivariate analysis including somatic gene analysis and tumor sidedness, no statistically significant differences at the gene or pathway level were demonstrated. Among advanced microsatellite stable CRCs, chemotherapy response and survival were equivalent by age cohorts. Pathogenic germline variants were identified in 23.3% of patients 35 years and younger vs 14.1% of AO-CRC (P = .01).
Conclusions
EO-CRCs are more commonly left-sided and present with rectal bleeding and abdominal pain but are otherwise clinically and genomically indistinguishable from AO-CRCs. Aggressive treatment regimens based solely on the age at CRC diagnosis are not warranted.
Funder
National Cancer Institute National Institutes of Health Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research Marie-Josée and Henry R. Kravis Center for Molecular Oncology Precision, Interception and Prevention Program at MSK Romeo Milio Lynch Syndrome Foundation
Publisher
Oxford University Press (OUP)
Subject
Cancer Research,Oncology
Cited by
60 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|