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Clin Colon Rectal Surg
DOI: 10.1055/s-0044-1787883
Review Article

The Young: Early-Onset Colon Cancer

David Cohen
1   Department of Surgery, New York-Presbyterian/Columbia University Irving Medical Center, New York, New York
,
Caitlin Rogers
2   Herbert Irving Comprehensive Cancer Research Center, Columbia University, New York, New York
,
Joel Gabre
2   Herbert Irving Comprehensive Cancer Research Center, Columbia University, New York, New York
3   Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York
,
Beatrice Dionigi
4   Division of Colon and Rectal Surgery, New York-Presbyterian/Columbia University Medical Center, New York, New York
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Abstract

Early-onset colorectal cancer (EO-CRC), characterized by diagnosis before the age of 50 years, has emerged as a significant healthcare challenge with increasing global incidence. While traditional risk factors such as family history and inherited syndromes contribute to EO-CRC, a substantial proportion of cases remain sporadic, necessitating further investigation into additional etiological factors. Molecular studies reveal heterogeneity in EO-CRC, with distinct mutational profiles compared to late-onset CRC. Clinical management presents unique considerations, including challenges in early detection and treatment strategies tailored to younger patients. Addressing EO-CRC requires a multidisciplinary approach integrating epidemiological, molecular, and clinical insights to improve prevention, diagnosis, and therapeutic outcomes. Emerging research avenues explore novel biomarkers and therapeutic targets, offering promise for advancing understanding and management of this disease in contemporary oncology practice.

Keywords

colon cancer - rectal cancer - early-onset cancer


Publication History

Article published online:
02 July 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Bhandari A, Woodhouse M, Gupta S. Colorectal cancer is a leading cause of cancer incidence and mortality among adults younger than 50 years in the USA: a SEER-based analysis with comparison to other young-onset cancers. J Investig Med 2017; 65 (02) 311-315
    CrossrefPubMedGoogle Scholar
  • 2 Vuik FER, Nieuwenburg SAV, Bardou M. et al. Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years. Gut 2019; 68 (10) 1820-1826
    CrossrefPubMedGoogle Scholar
  • 3 Marx O, Mankarious M, Yochum G. Molecular genetics of early-onset colorectal cancer. World J Biol Chem 2023; 14 (02) 13-27
    CrossrefPubMedGoogle Scholar
  • 4 Siegel RL, Miller KD, Goding Sauer A. et al. Colorectal cancer statistics, 2020. CA Cancer J Clin 2020; 70 (03) 145-164
    CrossrefPubMedGoogle Scholar
  • 5 Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin 2023; 73 (03) 233-254
    CrossrefPubMedGoogle Scholar
  • 6 Mauri G, Sartore-Bianchi A, Russo AG, Marsoni S, Bardelli A, Siena S. Early-onset colorectal cancer in young individuals. Mol Oncol 2019; 13 (02) 109-131
    CrossrefPubMedGoogle Scholar
  • 7 Bailey CE, Hu CY, You YN. et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg 2015; 150 (01) 17-22
    CrossrefPubMedGoogle Scholar
  • 8 Anderson JC, Samadder JN. To screen or not to screen adults 45–49 years of age: That is the question. Am J Gastroenterol 2018; 113 (12) 1750-1753
    CrossrefPubMedGoogle Scholar
  • 9 Ullah F, Pillai AB, Omar N, Dima D, Harichand S. Early-onset colorectal cancer: current insights. Cancers (Basel) 2023; 15 (12) 3202
    CrossrefPubMedGoogle Scholar
  • 10 Stoffel EM, Koeppe E, Everett J. et al. Germline genetic features of young individuals with colorectal cancer. Gastroenterology 2018; 154 (04) 897-905.e1
    CrossrefPubMedGoogle Scholar
  • 11 Gausman V, Dornblaser D, Anand S. et al. Risk factors associated with early-onset colorectal cancer. Clin Gastroenterol Hepatol 2020; 18 (12) 2752-2759.e2
    CrossrefPubMedGoogle Scholar
  • 12 Siegel RL, Fedewa SA, Anderson WF. et al. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst 2017; 109 (08) djw322
    CrossrefPubMedGoogle Scholar
  • 13 Akimoto N, Ugai T, Zhong R. et al. Rising incidence of early-onset colorectal cancer - a call to action. Nat Rev Clin Oncol 2021; 18 (04) 230-243
    CrossrefPubMedGoogle Scholar
  • 14 Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol 2022; 7 (03) 262-274
    CrossrefPubMedGoogle Scholar
  • 15 O'Sullivan DE, Sutherland RL, Town S. et al. Risk factors for early-onset colorectal cancer: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2022; 20 (06) 1229-1240.e5
    CrossrefPubMedGoogle Scholar
  • 16 Li H, Boakye D, Chen X. et al Associations of body mass index at different ages with early-onset colorectal cancer. Gastroenterology 2022; 162 (04) 1088-1097.e3
    CrossrefPubMedGoogle Scholar
  • 17 Pearlman R, Frankel WL, Swanson B. et al; Ohio Colorectal Cancer Prevention Initiative Study Group. Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol 2017; 3 (04) 464-471
    CrossrefPubMedGoogle Scholar
  • 18 Strum WB, Boland CR. Clinical and genetic characteristics of colorectal cancer in persons under 50 years of age: a review. Dig Dis Sci 2019; 64 (11) 3059-3065
    CrossrefPubMedGoogle Scholar
  • 19 de la Chapelle A, Hampel H. Clinical relevance of microsatellite instability in colorectal cancer. J Clin Oncol 2010; 28 (20) 3380-3387
    CrossrefPubMedGoogle Scholar
  • 20 Yan HHN, Siu HC, Ho SL. et al. Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles. Gut 2020; 69 (12) 2165-2179
    CrossrefPubMedGoogle Scholar
  • 21 Willauer AN, Liu Y, Pereira AAL. et al. Clinical and molecular characterization of early-onset colorectal cancer. Cancer 2019; 125 (12) 2002-2010
    CrossrefPubMedGoogle Scholar
  • 22 Xu T, Zhang Y, Zhang J. et al. Germline profiling and molecular characterization of early onset metastatic colorectal cancer. Front Oncol 2020; 10: 568911
    CrossrefPubMedGoogle Scholar
  • 23 Fodde R, Smits R, Clevers H. APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 2001; 1 (01) 55-67
    CrossrefPubMedGoogle Scholar
  • 24 Kirzin S, Marisa L, Guimbaud R. et al. Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study. PLoS One 2014; 9 (08) e103159
    CrossrefPubMedGoogle Scholar
  • 25 Guerrero RM, Labajos VA, Ballena SL. et al. Targeting BRAF V600E in metastatic colorectal cancer: where are we today?. Ecancermedicalscience 2022; 16: 1489
    PubMedGoogle Scholar
  • 26 Antelo M, Balaguer F, Shia J. et al. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer. PLoS One 2012; 7 (09) e45357
    CrossrefPubMedGoogle Scholar
  • 27 Guinney J, Dienstmann R, Wang X. et al. The consensus molecular subtypes of colorectal cancer. Nat Med 2015; 21 (11) 1350-1356
    CrossrefPubMedGoogle Scholar
  • 28 Wolf AMD, Fontham ETH, Church TR. et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin 2018; 68 (04) 250-281
    CrossrefPubMedGoogle Scholar
  • 29 Chung DC, Gray II DM, Singh H. et al. A cell-free DNA blood-based test for colorectal cancer screening. N Engl J Med 2024; 390 (11) 973-983
    CrossrefPubMedGoogle Scholar
  • 30 Fritz CDL, Otegbeye EE, Zong X. et al. Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer. J Natl Cancer Inst 2023; 115 (08) 909-916
    CrossrefPubMedGoogle Scholar
  • 31 Liang J, Kalady MF, Church J. Young age of onset colorectal cancers. Int J Colorectal Dis 2015; 30 (12) 1653-1657
    CrossrefPubMedGoogle Scholar
  • 32 Dozois EJ, Boardman LA, Suwanthanma W. et al. Young-onset colorectal cancer in patients with no known genetic predisposition: can we increase early recognition and improve outcome?. Medicine (Baltimore) 2008; 87 (05) 259-263
    CrossrefPubMedGoogle Scholar
  • 33 Frostberg E, Rahr HB. Clinical characteristics and a rising incidence of early-onset colorectal cancer in a nationwide cohort of 521 patients aged 18-40 years. Cancer Epidemiol 2020; 66: 101704
    CrossrefPubMedGoogle Scholar
  • 34 Shapley M, Mansell G, Jordan JL, Jordan KP. Positive predictive values of ≥5% in primary care for cancer: systematic review. Br J Gen Pract 2010; 60 (578) e366-e377
    CrossrefPubMedGoogle Scholar
  • 35 Hassab TH, Segev L, Kalady MF, Church JM. Distribution of colorectal cancer in young African Americans: implications for the choice of screening test. Int J Colorectal Dis 2019; 34 (08) 1477-1482
    CrossrefPubMedGoogle Scholar
  • 36 Gimeno Garcia AZ, Hernandez Alvarez Buylla N, Nicolas-Perez D, Quintero E. Public awareness of colorectal cancer screening: knowledge, attitudes, and interventions for increasing screening uptake. ISRN Oncol 2014; 2014: 425787
    PubMedGoogle Scholar
  • 37 Gimeno García AZ. Factors influencing colorectal cancer screening participation. Gastroenterol Res Pract 2012; 2012: 483417
    CrossrefPubMedGoogle Scholar
  • 38 Rattay KT, Henry LMG, Killingsworth RE. Colorectal cancer test use among Hispanic and non-Hispanic U.S. populations. Del J Public Health 2017; 3 (02) 52-56
    PubMedGoogle Scholar
  • 39 Gao XH, Li J, Liu LJ. et al. Trends, clinicopathological features, surgical treatment patterns and prognoses of early-onset versus late-onset colorectal cancer: a retrospective cohort study on 34067 patients managed from 2000 to 2021 in a Chinese tertiary center. Int J Surg 2022; 104: 106780
    CrossrefPubMedGoogle Scholar
  • 40 Holowatyj AN, Eng C, Lewis MA. Incorporating reproductive health in the clinical management of early-onset colorectal cancer. JCO Oncol Pract 2022; 18 (03) 169-172
    CrossrefPubMedGoogle Scholar
  • 41 NCCN Guidelines for Patients Survivorship Care for Cancer-Related Late and Long-Term Effects, National Comprehensive Cancer Network, Inc, 2021
    PubMed
  • 42 Survivorship Care for Cancer-Related Late and Long-Term Effects. 2021
    PubMedGoogle Scholar
  • 43 Carter J, Lacchetti C, Andersen BL. et al. Interventions to address sexual problems in people with cancer: American society of clinical oncology clinical practice guideline adaptation of cancer care Ontario guideline. J Clin Oncol 2018; 36 (05) 492-511
    CrossrefPubMedGoogle Scholar
  • 44 Stal J, Yi SY, Cohen-Cutler S. et al. Sexual dysfunction among early-onset colorectal cancer survivors: sex-specific correlates of sexual health discussions between patients and providers. Cancer Causes Control 2024; 35 (01) 111-120
    CrossrefPubMedGoogle Scholar
  • 45 Levi M, Shalgi R, Brenner B. et al. The impact of oxaliplatin on the gonads: from bedside to the bench. Mol Hum Reprod 2015; 21 (12) 885-893
    CrossrefPubMedGoogle Scholar
  • 46 Cercek A, Siegel CL, Capanu M, Reidy-Lagunes D, Saltz LB. Incidence of chemotherapy-induced amenorrhea in premenopausal women treated with adjuvant FOLFOX for colorectal cancer. Clin Colorectal Cancer 2013; 12 (03) 163-167
    CrossrefPubMedGoogle Scholar
  • 47 Kort JD, Eisenberg ML, Millheiser LS, Westphal LM. Fertility issues in cancer survivorship. CA Cancer J Clin 2014; 64 (02) 118-134
    CrossrefPubMedGoogle Scholar
  • 48 Maltaris T, Seufert R, Fischl F. et al. The effect of cancer treatment on female fertility and strategies for preserving fertility. Eur J Obstet Gynecol Reprod Biol 2007; 130 (02) 148-155
    CrossrefPubMedGoogle Scholar
  • 49 Shandley LM, McKenzie LJ. Recent advances in fertility preservation and counseling for reproductive-aged women with colorectal cancer: a systematic review. Dis Colon Rectum 2019; 62 (06) 762-771
    CrossrefPubMedGoogle Scholar
  • 50 Gubbala K, Laios A, Gallos I, Pathiraja P, Haldar K, Ind T. Outcomes of ovarian transposition in gynaecological cancers; a systematic review and meta-analysis. J Ovarian Res 2014; 7 (01) 69
    CrossrefPubMedGoogle Scholar
  • 51 Moawad NS, Santamaria E, Rhoton-Vlasak A, Lightsey JL. Laparoscopic ovarian transposition before pelvic cancer treatment: ovarian function and fertility preservation. J Minim Invasive Gynecol 2017; 24 (01) 28-35
    CrossrefPubMedGoogle Scholar
  • 52 Ribeiro R, Baiocchi G, Moretti-Marques R, Linhares JC, Costa CN, Pareja R. Uterine transposition for fertility and ovarian function preservation after radiotherapy. Int J Gynecol Cancer 2023; 33 (12) 1837-1842
    CrossrefPubMedGoogle Scholar
  • 53 Hanna NN, Cohen AM. Ovarian neoplasms in patients with colorectal cancer: understanding the role of prophylactic oophorectomy. Clin Colorectal Cancer 2004; 3 (04) 215-222
    CrossrefPubMedGoogle Scholar
  • 54 Demopoulos RI, Touger L, Dubin N. Secondary ovarian carcinoma: a clinical and pathological evaluation. Int J Gynecol Pathol 1987; 6 (02) 166-175
    CrossrefPubMedGoogle Scholar
  • 55 Banerjee S, Kapur S, Moran BJ. The role of prophylactic oophorectomy in women undergoing surgery for colorectal cancer. Colorectal Dis 2005; 7 (03) 214-217
    CrossrefPubMedGoogle Scholar
  • 56 Does the ACA require infertility treatment to be covered by health insurance? | healthinsurance.org. Accessed February 5, 2024 at: https://www.healthinsurance.org/faqs/does-the-aca-require-infertility-treatment-to-be-covered-by-health-insurance/
    PubMedGoogle Scholar
  • 57 Ugai T, Väyrynen JP, Lau MC. et al. Immune cell profiles in the tumor microenvironment of early-onset, intermediate-onset, and later-onset colorectal cancer. Cancer Immunol Immunother 2022; 71 (04) 933-942
    CrossrefPubMedGoogle Scholar
  • 58 Gardner IH, Siddharthan R, Watson K. et al. A distinct innate immune signature of early onset colorectal cancer. Immunohorizons 2021; 5 (06) 489-499
    CrossrefPubMedGoogle Scholar
  • 59 Sina C, Kemper C, Derer S. The intestinal complement system in inflammatory bowel disease: shaping intestinal barrier function. Semin Immunol 2018; 37: 66-73
    CrossrefPubMedGoogle Scholar