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.
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.
Authors: S J Winawer; R H Fletcher; L Miller; F Godlee; M H Stolar; C D Mulrow; S H Woolf; S N Glick; T G Ganiats; J H Bond; L Rosen; J G Zapka; S J Olsen; F M Giardiello; J E Sisk; R Van Antwerp; C Brown-Davis; D A Marciniak; R J Mayer Journal: Gastroenterology Date: 1997-02 Impact factor: 22.682
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Authors: Diana Mandelker; Liying Zhang; Yelena Kemel; Zsofia K Stadler; Vijai Joseph; Ahmet Zehir; Nisha Pradhan; Angela Arnold; Michael F Walsh; Yirong Li; Anoop R Balakrishnan; Aijazuddin Syed; Meera Prasad; Khedoudja Nafa; Maria I Carlo; Karen A Cadoo; Meg Sheehan; Megan H Fleischut; Erin Salo-Mullen; Magan Trottier; Steven M Lipkin; Anne Lincoln; Semanti Mukherjee; Vignesh Ravichandran; Roy Cambria; Jesse Galle; Wassim Abida; Marcia E Arcila; Ryma Benayed; Ronak Shah; Kenneth Yu; Dean F Bajorin; Jonathan A Coleman; Steven D Leach; Maeve A Lowery; Julio Garcia-Aguilar; Philip W Kantoff; Charles L Sawyers; Maura N Dickler; Leonard Saltz; Robert J Motzer; Eileen M O'Reilly; Howard I Scher; Jose Baselga; David S Klimstra; David B Solit; David M Hyman; Michael F Berger; Marc Ladanyi; Mark E Robson; Kenneth Offit Journal: JAMA Date: 2017-09-05 Impact factor: 56.272
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Authors: Shirley A A Beresford; Karen C Johnson; Cheryl Ritenbaugh; Norman L Lasser; Linda G Snetselaar; Henry R Black; Garnet L Anderson; Annlouise R Assaf; Tamsen Bassford; Deborah Bowen; Robert L Brunner; Robert G Brzyski; Bette Caan; Rowan T Chlebowski; Margery Gass; Rosanne C Harrigan; Jennifer Hays; David Heber; Gerardo Heiss; Susan L Hendrix; Barbara V Howard; Judith Hsia; F Allan Hubbell; Rebecca D Jackson; Jane Morley Kotchen; Lewis H Kuller; Andrea Z LaCroix; Dorothy S Lane; Robert D Langer; Cora E Lewis; JoAnn E Manson; Karen L Margolis; Yasmin Mossavar-Rahmani; Judith K Ockene; Linda M Parker; Michael G Perri; Lawrence Phillips; Ross L Prentice; John Robbins; Jacques E Rossouw; Gloria E Sarto; Marcia L Stefanick; Linda Van Horn; Mara Z Vitolins; Jean Wactawski-Wende; Robert B Wallace; Evelyn Whitlock Journal: JAMA Date: 2006-02-08 Impact factor: 56.272
Authors: Ahmet Zehir; Jaclyn F Hechtman; Sumit Middha; Liying Zhang; Khedoudja Nafa; Gowtham Jayakumaran; Donna Wong; Hyunjae R Kim; Justyna Sadowska; Michael F Berger; Deborah F Delair; Jinru Shia; Zsofia Stadler; David S Klimstra; Marc Ladanyi Journal: JCO Precis Oncol Date: 2017-10-03
Authors: Marla Lipsyc-Sharf; Sui Zhang; Fang-Shu Ou; Chao Ma; Nadine Jackson McCleary; Donna Niedzwiecki; I-Wen Chang; Heinz-Josef Lenz; Charles D Blanke; Sorbarikor Piawah; Katherine Van Loon; Tiffany M Bainter; Alan P Venook; Robert J Mayer; Charles S Fuchs; Federico Innocenti; Andrew B Nixon; Richard Goldberg; Eileen M O'Reilly; Jeffrey A Meyerhardt; Kimmie Ng Journal: J Natl Cancer Inst Date: 2022-03-08 Impact factor: 11.816