TY - JOUR
T1 - Is it all Lynch syndrome?
T2 - An assessment of family history in individuals with mismatch repair-deficient tumors
AU - Dempsey, Katherine M.
AU - Broaddus, Russell
AU - You, Y. Nancy
AU - Noblin, Sarah Jane
AU - Mork, Maureen
AU - Fellman, Bryan
AU - Urbauer, Diana
AU - Daniels, Molly
AU - Lu, Karen
N1 - Publisher Copyright:
© 2015 American College of Medical Genetics and Genomics.
PY - 2015/6/4
Y1 - 2015/6/4
N2 - 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 or BRAF mutation). Family histories were analyzed utilizing MMRpro and PREMM 1,2,6. 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, PREMM 1,2,6 = 7.3) than did LS individuals (MMRpro = 89.8, PREMM 1,2,6 = 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.
AB - 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 or BRAF mutation). Family histories were analyzed utilizing MMRpro and PREMM 1,2,6. 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, PREMM 1,2,6 = 7.3) than did LS individuals (MMRpro = 89.8, PREMM 1,2,6 = 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.
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U2 - 10.1038/gim.2014.131
DO - 10.1038/gim.2014.131
M3 - Article
C2 - 25341111
AN - SCOPUS:84930332689
SN - 1098-3600
VL - 17
SP - 476
EP - 484
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 6
ER -