Colorectal Cancer in Young Adults
- 42 Downloads
Purpose of review
Routine screening for colorectal cancer (CRC) in adults > 50 years of age has led to overall reductions in CRC incidence and CRC-related mortality. Yet CRC incidence among young adults age < 50 continues to increase without a clear explanation. This review examines the changing epidemiology of CRC and emerging evidence regarding the influence of genetic and lifestyle factors on risk for colorectal neoplasia.
Young-onset CRC (yCRC), defined as CRC diagnosed in individuals younger than age 50, is a heterogeneous disease. Approximately, one in every five individuals affected with yCRC carries a pathogenic germline variant in genes associated with predisposition to cancer. However, most have no clinically identifiable risk factors. Analyses of birth cohorts estimate CRC risk among millennials to be 2–4 times higher than their grandparents’, suggesting that changes in health behaviors and environmental factors are having an impact on CRC risk. Young individuals with CRC tend to be diagnosed at later stages and often present with metastatic disease. yCRC tumors arise predominantly in the distal colon and are more likely than older-onset tumors to exhibit microsatellite and chromosome stable (MACS) phenotypes. Although yCRC patients are more likely than their older counterparts to be treated with multimodality chemotherapy regimens, more aggressive treatments have not yielded measurable survival gains. Since one in ten new CRC diagnoses involve individuals age < 50, recent guidelines have proposed lowering the age for average risk CRC screening from 50 to 45; however, further studies are needed to evaluate testing strategies based on individuals’ age and risk.
Significant shifts in CRC epidemiology and diversity of tumor phenotypes support genetic and environmental factors as modifiers of cancer risk. Emerging data correlating tumor molecular features with outcomes justify further investigation into mechanisms of carcinogenesis to elucidate how specific factors (inherited and/or acquired) might stimulate young-onset colorectal neoplasia.
KeywordsColorectal cancer Screening Genetics
Compliance with Ethical Standards
Conflict of Interest
Anand Venugopal declares that he has no conflict of interest.
Elena Stoffel declares that she has 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.
References and Recommended Readings
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Cancer facts & figures 2018. Atlanta, Georgia: American Cancer Society2018. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-andstatistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf.
- 2.Colorectal cancer facts & figures 2017-2019. Atlanta, Georgia: American Cancer Society2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-andstatistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2017-2019.pdf.
- 5.• Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, et al. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst. 2017;109(8):djw322. https://doi.org/10.1093/jnci/djw322 This analysis highlights the significant differences in CRC incidence across age groups as well as annual percentage change in incidence by age.Google Scholar
- 6.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(2):311–5. https://doi.org/10.1136/jim-2016-000229.CrossRefGoogle Scholar
- 8.Yeo H, Betel D, Abelson JS, Zheng XE, Yantiss R, Shah MA. Early-onset colorectal cancer is distinct from traditional colorectal cancer. Clin Colorectal Cancer. 2017;16(4):293–9 e6. https://doi.org/10.1016/j.clcc.2017.06.002.
- 9.• Murphy CC, Lund JL, Sandler RS. Young-onset colorectal cancer: earlier diagnoses or increasing disease burden? Gastroenterology. 2017;152(8):1809–12 e3. https://doi.org/10.1053/j.gastro.2017.04.030 This study investigates the association between use of colonoscopy over the past two decades and its correlation with the increased incidence of yCRC. It finds that while initial rates of colonoscopy were increasing in parallel with the increasing incidence of yCRC, these two trends diverge around 2009 implying that increasing colonoscopy use does not explain the increasing yCRC incidence.CrossRefGoogle Scholar
- 10.Murphy CC, Sanoff HK, Stitzenberg KB, Baron JA, Lund JL, Sandler RS. 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;2017:4024580–10. https://doi.org/10.1155/2017/4024580.CrossRefGoogle Scholar
- 12.•• Wolf AMD, Fontham ETH, Church TR, Flowers CR, Guerra CE, LaMonte SJ, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250–81. https://doi.org/10.3322/caac.21457 This guideline recommended lowering the CRC screening age for asymptomatic average risk individuals from 50 to 45, generating debate.CrossRefGoogle Scholar
- 23.• Rho YS, Gilabert M, Polom K, Aladashvili A, Kopeckova K, Megdanova V, et al. Comparing clinical characteristics and outcomes of young-onset and late-onset colorectal cancer: an international collaborative study. Clin Colorectal Cancer. 2017;16(4):334–42. https://doi.org/10.1016/j.clcc.2017.03.008 This international, multicenter analysis looked at differences in use of adjuvant treatments for yCRC.CrossRefGoogle Scholar
- 24.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(8):1128–39. https://doi.org/10.1038/modpathol.2012.61.CrossRefGoogle Scholar
- 25.Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6:479–507. https://doi.org/10.1146/annurev-pathol-011110-130235.CrossRefGoogle Scholar
- 31.Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349(3):247–57. https://doi.org/10.1056/NEJMoa022289.CrossRefGoogle Scholar
- 33.Schellerer VS, Merkel S, Schumann SC, Schlabrakowski A, Fortsch T, Schildberg C, et al. Despite aggressive histopathology survival is not impaired in young patients with colorectal cancer : CRC in patients under 50 years of age. Int J Color Dis. 2012;27(1):71–9. https://doi.org/10.1007/s00384-011-1291-8.CrossRefGoogle Scholar
- 34.• Kneuertz PJ, Chang GJ, Hu CY, Rodriguez-Bigas MA, Eng C, Vilar E, et al. Overtreatment of young adults with colon cancer: more intense treatments with unmatched survival gains. JAMA Surg. 2015;150(5):402–9. https://doi.org/10.1001/jamasurg.2014.3572 Analysis of hospital system data found yCRC patients were significantly more likely to receive high intensity multimodality chemotherapy without associated surival gains.CrossRefGoogle Scholar
- 35.•• Manjelievskaia J, Brown D, Mc Glynn KA, Anderson W, Shriver CD, Zhu K. Chemotherapy use and survival among young and middle-aged patients with colon cancer. JAMA Surg. 2017;152(5):452–9. https://doi.org/10.1001/jamasurg.2016.5050 This study highlights differences in the treatment approaches for yCRC. It describes an increase in use of adjuvant chemotherapy for yCRC patients compared to oldercounterparts with no differences in outcomes. The authors propose a potential overuse of chemotherapy among young patients with CRC.CrossRefGoogle Scholar
- 36.Puccini A, Lenz HJ, Marshall JL, Arguello D, Raghavan D, Korn WM, Weinberg BA, Poorman K, Heeke AL, Philip PA, Shields AF, Goldberg RM, Salem ME Impact of patient age on molecular alterations of left-sided colorectal tumors. The Oncologist 2018. https://doi.org/10.1634/theoncologist.2018-0117, theoncologist.2018, theoncologist.0117.
- 39.Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. American College of Gastroenterology ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes. Am J Gastroenterol. 2015;110(2):223–62; quiz 63. https://doi.org/10.1038/ajg.2014.435.
- 40.Genetic/familial high-risk assessment: Colorectal. In: NCCN Clinical Practice Guidelines in Oncology. 2018. https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. Accessed 11/3/2018 2018.
- 41.•• Stoffel EM, Koeppe E, Everett J, Ulintz P, Kiel M, Osborne J, et al. Germline genetic features of young individuals with colorectal cancer. Gastroenterology. 2018;154(4):897–905 e1. https://doi.org/10.1053/j.gastro.2017.11.004 This analysis of outcomes of germline sequencing in patients referred to a cancer genetics clinic found 1 in 5 yCRC patients had pathogenic germline variants in common CRC genes, many of whom reported no family history of CRC.CrossRefGoogle Scholar
- 45.de Kort S, Masclee AAM, Sanduleanu S, Weijenberg MP, van Herk-Sukel MPP, Oldenhof NJJ, et al. Higher risk of colorectal cancer in patients with newly diagnosed diabetes mellitus before the age of colorectal cancer screening initiation. Sci Rep. 2017;7:46527. https://doi.org/10.1038/srep46527.CrossRefGoogle Scholar
- 51.Rex DK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. multi-society task force on colorectal cancer. Gastroenterology. 2017;153(1):307–23. https://doi.org/10.1053/j.gastro.2017.05.013.CrossRefGoogle Scholar
- 54.•• Peterse EFP, Meester RGS, Siegel RL, Chen JC, Dwyer A, Ahnen DJ, et al. The impact of the rising colorectal cancer incidence in young adults on the optimal age to start screening: microsimulation analysis I to inform the American Cancer Society colorectal cancer screening guideline. Cancer. 2018;124(14):2964–73. https://doi.org/10.1002/cncr.31543 This analysis incoorporates contemporary CRC incidence data to model outcomes of CRC screening to justify offering screening for CRC at an earlier age.CrossRefGoogle Scholar