lunes, 3 de noviembre de 2014

Is it all Lynch syndrome?: An assessment of family history in individuals with mismatch repair-deficient tumors : Genetics in Medicine : Nature Publishing Group

Is it all Lynch syndrome?: An assessment of family history in individuals with mismatch repair-deficient tumors : Genetics in Medicine : Nature Publishing Group



Is it all Lynch syndrome?: An assessment of family history in individuals with mismatch repair–deficient tumors

Genetics in Medicine
 
(2014)
 
doi:10.1038/gim.2014.131
Received
 
Accepted
 
Published online 

Abstract

Purpose:

Mismatch repair-deficient (MMRD) colorectal cancer (CRC) and endometrial cancer (EC) may be suggestive of Lynch syndrome (LS). LS can be confirmed only by positive germ-line testing. It is unclear if individuals with MMRD tumors but no identifiable cause (MMRD+/germ-line−) have LS. Because LS is hereditary, individuals with LS are expected to have family histories of LS-related tumors. Our study compared the family histories of MMRD+/germ-line− CRC and/or EC patients with LS CRC and/or EC patients.

Methods:

A total of 253 individuals with an MMRD CRC or EC from one institution were included for analysis in one of four groups: LS; MMRD+/germ-line−; MMRD tumor with variant of uncertain significance (MMRD+/VUS); and sporadic MSI-H (MMRD tumor with MLH1 promoter hypermethylation orBRAF mutation). Family histories were analyzed utilizing MMRpro and PREMM1,2,6. Kruskal–Wallis tests were used to compare family history scores.

Results:

MMRD+/germ-line− individuals had significantly lower median family history scores (MMRpro = 8.1, PREMM1,2,6 = 7.3) than did LS individuals (MMRpro = 89.8, PREMM1,2,6 = 26.1, P < 0.0001).

Conclusion:

MMRD+/germ-line− individuals have less suggestive family histories of LS than individuals with LS. These results imply that MMRD+/germ-line− individuals may not all have LS. This finding highlights the need to determine other causes of MMRD tumors so that these patients and their families can be accurately counseled regarding screening and management.
Genet Med advance online publication 23 October 2014

Keywords:

 
genetic testing; Lynch syndrome; mismatch repair–deficient tumor; tumor studies

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Author information

Affiliations

  1. Department of Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    • Katherine M. Dempsey,
    •  
    • Maureen Mork,
    •  
    • Molly Daniels &
    •  
    • Karen Lu
  2. Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    • Katherine M. Dempsey &
    •  
    • Molly Daniels
  3. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA

    • Katherine M. Dempsey,
    •  
    • Russell Broaddus,
    •  
    • Sarah Jane Noblin,
    •  
    • Molly Daniels &
    •  
    • Karen Lu
  4. Department of Pathology Administration, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    • Russell Broaddus
  5. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    • Y. Nancy You &
    •  
    • Maureen Mork
  6. Department of Obstetrics and Gynecology, The University of Texas Health Science Center at Houston, Houston, Texas, USA

    • Sarah Jane Noblin
  7. Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas, USA

    • Sarah Jane Noblin &
    •  
    • Molly Daniels
  8. Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    • Bryan Fellman &
    •  
    • Diana Urbauer

Corresponding author

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