Early Onset Metastatic Colorectal Cancer: Current Insights and Clinical Management of a Rising Condition

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Jul 14

PMID 37444619

Authors

Bianca Medici

Beatrice Ricco

Eugenia Caffari

Silvia Zaniboni

Massimiliano Salati

Andrea Spallanzani

Ingrid Garajova

Stefania Benatti

Chiara Chiavelli

Massimo Dominici

Fabio Gelsomino

Affiliations

Soon will be listed here.

Abstract

Despite a recent overall decrease in colorectal cancer (CRC) incidence and mortality, there has been a significant rise in CRC diagnoses in young adults. Early onset colorectal cancer (EOCRC) is defined as CRC diagnosed before the age of 50. Possible predisposing conditions include not only genetic syndromes but also other risk factors, such as microbiome alteration, antibiotic exposure, obesity, diabetes mellitus, and inflammatory bowel disease. EOCRC tends to be diagnosed later than in the older counterpart because of a lack of awareness and the fact that screening for CRC usually starts at the age of 50. Furthermore, CRC in young adults seems to be related to unique molecular features and more aggressive clinical behavior. This paper aims to provide an in-depth review of this poorly understood subject, with a comprehensive review of the state of the art and considerations for future perspectives.

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References

Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C . Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo.... J Clin Oncol. 2007; 25(13):1670-6. DOI: 10.1200/JCO.2006.09.0928. View

Saad El Din K, Loree J, Sayre E, Gill S, Brown C, Dau H . Trends in the epidemiology of young-onset colorectal cancer: a worldwide systematic review. BMC Cancer. 2020; 20(1):288. PMC: 7137305. DOI: 10.1186/s12885-020-06766-9. View

Siegel R, Jakubowski C, Fedewa S, Davis A, Azad N . Colorectal Cancer in the Young: Epidemiology, Prevention, Management. Am Soc Clin Oncol Educ Book. 2020; 40:1-14. DOI: 10.1200/EDBK_279901. View

Higurashi T, Hosono K, Takahashi H, Komiya Y, Umezawa S, Sakai E . Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016; 17(4):475-483. DOI: 10.1016/S1470-2045(15)00565-3. View

Southey M, Jenkins M, Mead L, Whitty J, Trivett M, Tesoriero A . Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer. J Clin Oncol. 2005; 23(27):6524-32. DOI: 10.1200/JCO.2005.04.671. View

Tunca B, Tezcan G, Cecener G, Egeli U, Zorluoglu A, Yilmazlar T . Overexpression of CK20, MAP3K8 and EIF5A correlates with poor prognosis in early-onset colorectal cancer patients. J Cancer Res Clin Oncol. 2013; 139(4):691-702. DOI: 10.1007/s00432-013-1372-x. View

Siegel R, Torre L, Soerjomataram I, Hayes R, Bray F, Weber T . Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019; 68(12):2179-2185. DOI: 10.1136/gutjnl-2019-319511. View

Abou-Zeid A, Jumuah W, Ebied E, Abd El Samee Atia K, Ghamrini Y, Somaie D . Hereditary factors are unlikely behind unusual pattern of early - Onset colorectal cancer in Egyptians: A study of family history and pathology features in Egyptians with large bowel cancer (cross-sectional study). Int J Surg. 2017; 44:71-75. DOI: 10.1016/j.ijsu.2017.06.028. View

Herman J, Umar A, Polyak K, Graff J, Ahuja N, Issa J . Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A. 1998; 95(12):6870-5. PMC: 22665. DOI: 10.1073/pnas.95.12.6870. View

10.

Siddique S, Tariq K, Rafiq S, Raheem A, Ahmed R, Shabbir-Moosajee M . Sporadic Early Onset Colorectal Cancer in Pakistan: a Case- Control Analysis of Microsatellite Instability. Asian Pac J Cancer Prev. 2016; 17(5):2587-92. View

11.

Stoffel E, Murphy C . Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults. Gastroenterology. 2019; 158(2):341-353. PMC: 6957715. DOI: 10.1053/j.gastro.2019.07.055. View

12.

Siegel R, Miller K, Jemal A . Colorectal Cancer Mortality Rates in Adults Aged 20 to 54 Years in the United States, 1970-2014. JAMA. 2017; 318(6):572-574. PMC: 5817468. DOI: 10.1001/jama.2017.7630. View

13.

Venugopal A, Carethers J . Epidemiology and biology of early onset colorectal cancer. EXCLI J. 2022; 21:162-182. PMC: 8859644. DOI: 10.17179/excli2021-4456. View

14.

Siegel R, Fedewa S, Anderson W, Miller K, Ma J, Rosenberg P . Colorectal Cancer Incidence Patterns in the United States, 1974-2013. J Natl Cancer Inst. 2017; 109(8). PMC: 6059239. DOI: 10.1093/jnci/djw322. View

15.

Dozois E, Boardman L, Suwanthanma W, Limburg P, Cima R, Bakken J . Young-onset colorectal cancer in patients with no known genetic predisposition: can we increase early recognition and improve outcome?. Medicine (Baltimore). 2008; 87(5):259-263. PMC: 4437192. DOI: 10.1097/MD.0b013e3181881354. View

16.

Taieb J, Svrcek M, Cohen R, Basile D, Tougeron D, Phelip J . Deficient mismatch repair/microsatellite unstable colorectal cancer: Diagnosis, prognosis and treatment. Eur J Cancer. 2022; 175:136-157. DOI: 10.1016/j.ejca.2022.07.020. View

17.

Meester R, Mannalithara A, Lansdorp-Vogelaar I, Ladabaum U . Trends in Incidence and Stage at Diagnosis of Colorectal Cancer in Adults Aged 40 Through 49 Years, 1975-2015. JAMA. 2019; 321(19):1933-1934. PMC: 6537839. DOI: 10.1001/jama.2019.3076. View

18.

Lynch H, Lynch J, Lynch P, Attard T . Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer. 2007; 7(1):27-39. DOI: 10.1007/s10689-007-9165-5. View

19.

Chan T, Curtis L, Leung S, Farrington S, Ho J, Chan A . Early-onset colorectal cancer with stable microsatellite DNA and near-diploid chromosomes. Oncogene. 2001; 20(35):4871-6. DOI: 10.1038/sj.onc.1204653. View

20.

Karapetis C, Khambata-Ford S, Jonker D, OCallaghan C, Tu D, Tebbutt N . K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17):1757-65. DOI: 10.1056/NEJMoa0804385. View