TITLE

Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma

AUTHOR(S)
Durno, C.; Aronson, M.; Bapat, B.; Cohen, Z.; Gallinger, S.
PUB. DATE
August 2005
SOURCE
Gut;Aug2005, Vol. 54 Issue 8, p1146
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Colorectal cancer is extremely rare in childhood. Published case series reporting children and adolescents with colorectal cancer have not focused on the underlying genetic aspects of the tumour or genetic susceptibility of the families. Aims: We examined a cohort of patients with early onset colorectal cancer to determine whether a specific genetic predisposition could be elucidated. In particular, we focused on whether DNA mismatch repair gene deficiency which causes hereditary non-polyposis colorectal cancer (HNPCC) could be elucidated. Methods: Patients with colorectal cancer ⩽ 24 years of age were identified from a database at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital, Toronto. Detailed pedigrees were ascertained from the proband or parents. Tumours were tested for microsatellite instability, a hallmark of HNPCC. Germline mismatch repair gene mutations (MSH2 and MLH1) were sought in some cases. Clinical data were obtained by chart audit. Results: Among 1382 probands in our registry, 16 (1%) colorectal cancer patients were 24 years or younger at the time of diagnosis. Microsatellite instability was identified in tumours from eight (73%) of 11 evaluated patients. Germline mutations in mismatch repair genes were identified in six of 12 patients, including MSH2 (n=3), MLH1 (n=2), and PMS2 (n= 1). Ten (63%) of 16 families met the Amsterdam criteria for HNPCC. Among these, six were screened for mismatch repair gene mutations and three were found to carry MSH2 or MLH1 germline mutations. Location of the colorectal cancers included rectum! sigmoid (n = 9), splenic flexure (n = 2), hepatic Hexure (n = 3), and caecum (n = 2). Forty four per cent (7/ 16) of these young cases developed additional malignancies (gastrointestinal (n = 8) and extraintestinal (n=4)) during follow up (mean 12.8 (SD 12.4) years (range 0.08-30)). Conclusions: Patients with early onset colorectal carcinoma often have an inherited predisposition to the disease. Tumours with high frequency microsatellite instability and germline mutations of mismatch repair genes are sufficiently common in this patient population that they should be considered, even though family histories may not satisfy the stringent Amsterdam criteria for HNPCC. Young colorectal cancer patients are at increased risk of developing second gastrointestinal and extraintestinal malignancies.
ACCESSION #
17814011

 

Related Articles

  • Claudin-7 expression induces mesenchymal to epithelial transformation (MET) to inhibit colon tumorigenesis. Bhat, A A; Pope, J L; Smith, J J; Ahmad, R; Chen, X; Washington, M K; Beauchamp, R D; Singh, A B; Dhawan, P // Oncogene;8/27/2015, Vol. 34 Issue 35, p4570 

    In normal colon, claudin-7 is one of the highly expressed claudin proteins and its knockdown in mice results in altered epithelial cell homeostasis and neonatal death. Notably, dysregulation of the epithelial homeostasis potentiates oncogenic transformation and growth. However, the role of...

  • BY THE NUMBERS.  // Hem/Onc Today;6/10/2012, Vol. 13 Issue 11, p1 

    A chart is presented that offers information on the increasing number of cardiac cases among survivors of childhood cancer who have undergone cardiotoxic therapy.

  • Retinoblastoma -- clinical and genetic aspects: a review. Cowell, J. K.; Hungerford, J.; Jay, M.; Rutland, P. // Journal of the Royal Society of Medicine;Apr1988, Vol. 81 Issue 4, p220 

    The article discusses the clinical and genetic aspects of retinoblastoma, a malignant ocular tumor involving the retinal cells. Most cases of retinoblastoma are apparently sporadic, but a significant proportion are familial and inheritance follows an autosomal dominant mode with high penetrance....

  • Colorectal Cancer in Young Adults. Inra, Jennifer; Syngal, Sapna // Digestive Diseases & Sciences;Mar2015, Vol. 60 Issue 3, p722 

    The incidence and mortality rates of colorectal cancer (CRC) have been decreasing in adults over 50 years of age, however, these rates have been increasing in adults under 50. The majority of CRC in young adults is sporadic, and is likely due to behavioral and environmental causes, however the...

  • Victory in cancer cure is not always as sweet as publicized. Coppes, Max J. // Hem/Onc Today;2/25/2014, Vol. 15 Issue 4, p30 

    The author offers insights on two studies which investigated ill effects of cancer in young patients, including one by Kevin R. Krull and colleagues that was published in the "Journal of Clinical Oncology," and another by Donghao Lu and colleagues that was featured in "Annals of Oncology" journal.

  • Interpretation of genome-wide infinium methylation data from ligated DNA in formalinfixed, paraffin-embedded paired tumor and normal tissue.  // BMC Research Notes;2012, Vol. 5 Issue 1, p117 

    The article presents information on a study which evaluates the accuracy of DNA methylation data obtained with a modified ligation-based DNA repair protocol by comparing paired fresh-frozen (FF) and FFPE colon tissue (normal and tumor) from colorectal cancer patients. The ligation-based DNA...

  • Childhood cancer incidence and survival in Spain. Peris-Bonet, R.; Salmer�n, D.; Mart�nez-Beneito, M. A.; Galceran, J.; Marcos-Gragera, R.; Felipe, S.; Gonz�lez, V.; S�nchez de Toledo Codina, J. // Annals of Oncology;May2010, Vol. 21 Issue suppl_3, piii103 

    Background: This article affords an overview of the patterns and time trends of childhood cancer incidence (1983�2002) and survival (1991�2002) in Spain.

  • Bone-mineral density deficits from childhood cancer and its therapy: A review of at-risk patient cohorts and available imaging methods. Kaste, Sue C. // Pediatric Radiology;May2004, Vol. 34 Issue 5, p373 

    The growing population of childhood cancer survivors—currently estimated at 1 in 900 young adults aged 15–45 years—underscores the importance of studying long-term complications of oncotherapy. While these patients are returning to the mainstream of life, they carry with...

  • SURVIVING THE CURE. SCUTTI, SUSAN // Newsweek Global;7/31/2015, Vol. 165 Issue 5, p132 

    The article reports that survivors of childhood cancer are at high risk for its long-term effects. Chemotherapy drugs and radiation destroy cancer cells but also damage the DNA of normal cells nearby. The resulting effects may include infertility, heart and cardiovascular problems,...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics