Familial Cancer

, Volume 9, Issue 2, pp 99–107 | Cite as

Evaluating Lynch syndrome in very early onset colorectal cancer probands without apparent polyposis

  • Kory W. Jasperson
  • Thuy M. Vu
  • Angela L. Schwab
  • Deborah W. Neklason
  • Miguel A. Rodriguez-Bigas
  • Randall W. Burt
  • Jeffrey N. Weitzel


To characterize the frequency of germline mutations associated with Lynch syndrome and review the potential expanded differential diagnoses in very early onset colorectal cancer (CRC) cases without apparent polyposis. Retrospectively reviewed medical records of 96 probands with CRC diagnosed prior to age 36 from three cancer centers. Determined the frequency of germline mutations in probands meeting different clinical criteria used to identify Lynch syndrome. Three of 46 (6.5%) single case indicators (probands without additional personal or family history suspicious for Lynch syndrome) were identified to carry a deleterious or suspected deleterious mismatch repair (MMR) mutation compared with 10 of 19 (52.6%) in the cases meeting at least one additional revised Bethesda guideline, and 11 of 15 (73.3%) in the cases meeting Amsterdam criteria. Two families without MMR mutations were documented to have a germline APC or TP53 mutation after additional clinical features were identified. Our results suggest that single cases of CRC (those without additional personal or family history suspicious of Lynch syndrome) diagnosed prior to age 36 infrequently have identifiable MMR mutations, especially when compared to cases meeting additional criteria. Careful attention to evolving or additional clinical features is warranted and may lead to an alternate genetic diagnosis in families with early onset CRC.


Attenuated familial adenomatous polyposis Early onset colorectal cancer HNPCC Genetic testing Li-Fraumeni syndrome Lynch syndrome Mismatch repair genes 



Amsterdam criteria


Attenuated familial adenomatous polyposis


Colorectal cancer




MYH associated polyposis


Mismatch repair


Microsatellite instability


Utah Population Database



We would like to thank the expert input from Katrina Lowstuter MS, CGC regarding this manuscript. This research was supported in part by a General Clinical Research Center grant from NIH (M01 RR00043) and by the National Cancer Institute, Grant No. R25 CA85771.


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Kory W. Jasperson
    • 1
    • 2
  • Thuy M. Vu
    • 3
  • Angela L. Schwab
    • 2
  • Deborah W. Neklason
    • 2
  • Miguel A. Rodriguez-Bigas
    • 3
  • Randall W. Burt
    • 2
  • Jeffrey N. Weitzel
    • 1
  1. 1.Cancer Screening & Prevention ProgramCity of Hope Cancer CenterDuarteUSA
  2. 2.Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  3. 3.Department of Clinical Cancer GeneticsUniversity of Texas MD Anderson Cancer CenterHoustonUSA

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