Colorectal Cancer in the Young
- 782 Downloads
Purpose of Review
Colorectal cancer incidence has been rapidly rising in those under the age of 50 over the last 20 years. This paper will review the epidemiology, clinicopathologic, molecular features, proposed risk factors, and prevention/treatment approach for early onset CRC (EOCRC) patients.
EOCRC appears to have a different spectrum of clinical, pathologic, and molecular presentation compared to CRC diagnosed in older individuals. EOCRCs are disproportionately located in the distal colon; these patients tend to present with symptoms, and there is a longer interval between symptoms and diagnosis. There may be a distinct molecular signature, including progression through the microsatellite and chromosomal stable (MACS) pathway and LINE-1 hypomethylation for a subset of EOCRCs. The majority of EOCRCs are sporadic without clear risk factors that would have made the patient eligible for earlier screening.
There is an acute need for educational efforts aimed at both providers and patients to raise awareness about CRC in the young. Improving adherence to screening in young patients eligible for screening and emphasizing early evaluation of symptoms are important steps to decreasing the burden of CRC in younger patients. Modeling and empiric data are needed to determine whether our current screening approach should be modified and whether causation and treatment options may be different in a molecular subset EOCRCs.
KeywordsColorectal cancer Lynch syndrome Adenoma Colonoscopy LINE-1 hypomethylation CpG island methylation Chromosomal instability Microsatellite instability
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 2.•• Siegel RL, Fedewa SA, Anderson WF, et al. Colorectal cancer incidence patterns in the United States, 1974–2013. J Natl Cancer Inst 2017;109. This is the latest in a series of papers by Siegel and colleagues documenting the increasing incidence of CRC in those under age 50 and for the first time showed that CRC risk has been increasing in sequential birth cohorts since 1990. Based on this date they reasoned that screening initiation before age 50 years should be considered in the average risk population. Google Scholar
- 8.Stoffel EM, Mangu PB, Limburg PJ, American Society of Clinical Oncology, European Society for Medical Oncology. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology clinical practice guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology clinical practice guidelines. J Oncol Pract. 2015;11:e437–41.CrossRefPubMedGoogle Scholar
- 27.Murphy CC, Sanoff HK, Stitzenberg KB, et al. Patterns of sociodemographic and clinicopathologic characteristics of stages II and III colorectal cancer patients by age: examining potential mechanisms of young-onset disease. J Cancer Epidemiol. 2017;2017:4024580.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Chang DT, Pai RK, Rybicki LA, Dimaio MA, Limaye M, Jayachandran P, et al. Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features. Mod Pathol. 2012;25:1128–39.CrossRefPubMedGoogle Scholar
- 29.•• Pearlman R, Frankel WL, Swanson B, et al. Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol. 2017;3:464–71. The authors report the results of germline genetic testing using a cancer panel in a series 450 patients diagnosed with colorectal cancer younger than 50 years who were prospectively accrued from 51 hospitals. They found a 16% rate of a pathogenic germline mutations and only half were due to Lynch syndrome. The results support the notion that all patients with EOCRC should be offered genetic counseling and gene testing with a broad cancer panel CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Stoffel EM, Koeppe E, Everett J, Ulintz P, Kiel M, Osborne J, et al. Germline genetic features of young individuals with colorectal cancer. Gastroenterology. 2017;Google Scholar
- 34.NCCN. NCCN Clinical Practice Guidelines in Oncology: Colorectal Cancer Screening. Volume 2014. http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf, 2013.
- 37.Statistics NCfH. Health, United States, 2016: with Chartbook on long-term trends in health. Hyattsville, MD. 2017, 2016.Google Scholar
- 38.Zheng J, Zhao M, Li J, Lou G, Yuan Y, Bu S, Xi Y Obesity-associated digestive cancers: a review of mechanisms and interventions. Tumour Biol 2017;39:1010428317695020, 101042831769502.Google Scholar
- 47.Thompson AB, Mowery PD, Tebes JK, et al. Time trends in smoking onset by sex and race/ethnicity among adolescents and young adults: findings from the 2006-2013 National Survey on drug use and health. Nicotine Tob Res. 2017;Google Scholar
- 48.Hemminki K, Chen B. Familial risk for colorectal cancers are mainly due to heritable causes. Cancer Epidemiol Biomark Prev. 2004;13:1253–6.Google Scholar
- 65.Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.PubMedGoogle Scholar
- 74.NCCN. Genetic/Familial High-Risk Assessment: Colorectal. National Comprehensive Cancer Network. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp, 2016.
- 75.Claes E, Denayer L, Evers-Kiebooms G, Boogaerts A, Philippe K, Tejpar S, et al. Predictive testing for hereditary nonpolyposis colorectal cancer: subjective perception regarding colorectal and endometrial cancer, distress, and health-related behavior at one year post-test. Genet Test. 2005;9:54–65.CrossRefPubMedGoogle Scholar
- 81.Patel SG, Ahnen DJ, Kinney AY, Horick N, Finkelstein DM, Hill DA, et al. Knowledge and uptake of genetic counseling and colonoscopic screening among individuals at increased risk for lynch syndrome and their endoscopists from the family health promotion project. Am J Gastroenterol. 2016;111:285–93.CrossRefPubMedPubMedCentralGoogle Scholar
- 83.Evaluation of Genomic Applications in P, Prevention Working G. Recommendations from the EGAPP working group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from lynch syndrome in relatives. Genet Med. 2009;11:35–41.CrossRefGoogle Scholar
- 90.Akhtar S, Sinha S, McKenzie S, Sagar PM, Finan PJ, Burke D. Awareness of risk factors amongst first degree relative patients with colorectal cancer. Color Dis. 2008;10:887–90.Google Scholar