Early-Age-of-Onset Colorectal Carcinoma: An Emerging Public Health Issue



The etiology of colorectal cancer (CRC) is complex and appears to involve a combination of underlying genetic susceptibility, somatic alterations, and environmental exposures which people experience since conception. Young age at diagnosis is a hallmark of hereditary cancer syndromes as discussed in the chapters that follow. Currently known genetic predispositions to CRC include Lynch syndrome (caused by germline mutations in DNA mismatch repair genes), familial adenomatous polyposis (due to APC mutations), MUTYH-associated polyposis (due to mutations in both alleles of MUTYH gene), and germline mutations in other genes such as SMAD4, BRCA1, TP53, POLE, and POLD1. However, only 20–30% of CRC diagnosed under age 50 are attributable to these known hereditary syndromes. The remaining majority of young adult CRC may be associated with other genetic predispositions which have yet to be identified, polygenic factors such as single-nucleotide polymorphisms (SNPs), and/or environmental and lifestyle factors of the person. An analysis of 450 patients diagnosed with CRC under the age of 50 detected 75 gene mutations in 72 patients for a mutation rate of 16%. Of note, 33% of the patients that had a gene mutation did not meet current guidelines for genetic testing. The high frequency and wide spectrum of mutations noted in this study support the argument for more routine multigene testing. In addition, these results are consistent with older studies demonstrating that the frequency of HNPCC (previous name for clinical diagnosis of Lynch syndrome) in CRC patients 40–45 years of age ranges between 15 and 20%, which is greater than a fourfold increase in the rate of HNPCC noted in non-age-stratified CRC.


Obesity Type 2 diabetes Colonoscopy Screening Immunohistochemical fecal occult blood test (iFOBT) Rectal bleeding Abdominal pain 


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global HealthCarltonAustralia
  2. 2.University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer CentreMelbourneAustralia
  3. 3.Faculty of Medicine, Dentistry and Health Sciences, The University of MelbourneParkvilleAustralia
  4. 4.Department of SurgeryMike O’Callaghan Federal Medical CenterLas VegasUSA
  5. 5.Department of SurgeryUniversity of Las Vegas- Nevada School of MedicineLas VegasUSA
  6. 6.Gastrointestinal Surgery, University of North CarolinaChapel HillUSA

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