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

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Management of Hereditary Colorectal Cancer

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Abstract

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.

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Author information

Authors and Affiliations

  1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Carlton, VIC, Australia

    Aung K. Win

  2. University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Melbourne, VIC, Australia

    Aung K. Win

  3. Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, Australia

    Aung K. Win

  4. Department of Surgery, Mike O’Callaghan Federal Medical Center, Las Vegas, NV, USA

    Garrett Friedman

  5. Department of Surgery, University of Las Vegas- Nevada School of Medicine, Las Vegas, NV, USA

    Garrett Friedman

  6. Gastrointestinal Surgery, University of North Carolina, Chapel Hill, NC, USA

    Jose G. Guillem

Authors
  1. Aung K. Win
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  2. Garrett Friedman
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  3. Jose G. Guillem
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Correspondence to Jose G. Guillem .

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Editors and Affiliations

  1. Gastrointestinal Surgery, University of North Carolina, Chapel Hill, NC, USA

    Jose G. Guillem

  2. Department of Surgery, Mike O’Callaghan Federal Medical Center, Las Vegas, NV, USA

    Garrett Friedman

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Win, A.K., Friedman, G., Guillem, J.G. (2020). Early-Age-of-Onset Colorectal Carcinoma: An Emerging Public Health Issue. In: Guillem, J., Friedman, G. (eds) Management of Hereditary Colorectal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-26234-1_1

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  • DOI: https://doi.org/10.1007/978-3-030-26234-1_1

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  • Online ISBN: 978-3-030-26234-1

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