TY - JOUR
T1 - Prospective statewide study of universal screening for hereditary colorectal cancer
T2 - The ohio colorectal cancer prevention initiative
AU - Pearlman, Rachel
AU - Frankel, Wendy L.
AU - Swanson, Benjamin J.
AU - Jones, Dan
AU - Zhao, Weiqiang
AU - Yilmaz, Ahmet
AU - Miller, Kristin
AU - Bacher, Jason
AU - Bigley, Christopher
AU - Nelsen, Lori
AU - Goodfellow, Paul J.
AU - Goldberg, Richard M.
AU - Paskett, Electra
AU - Shields, Peter G.
AU - Freudenheim, Jo L.
AU - Stanich, Peter P.
AU - Lattimer, Ilene
AU - Arnold, Mark
AU - Prior, Thomas W.
AU - Haut, Mitchell
AU - Kalady, Matthew F.
AU - Heald, Brandie
AU - Paquette, Ian
AU - Draper, David J.
AU - Brell, Joanna M.
AU - Mahesh, Sameer
AU - Weeman, Kisa
AU - Bastola, Shyamal
AU - Zangmeister, Jeffrey
AU - Gowda, Aruna
AU - Kencana, Filix
AU - Malcolm, Albert
AU - Liu, Yinong
AU - Cole, Sharon
AU - Bane, Charles
AU - Li, Chaoyang
AU - Rehmus, Esther
AU - Pritchard, Colin C.
AU - Shirts, Brian H.
AU - Jacobson, Angela
AU - Cummings, Shelly A.
AU - De la Chapelle, Albert
AU - Hampel, Heather
N1 - Publisher Copyright:
© 2021 American Society of Clinical Oncology. All rights reserved.
PY - 2021
Y1 - 2021
N2 - PURPOSE Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement. METHODS Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed , 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer. RESULTS Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred fortytwo (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional MLH1 hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets. CONCLUSION UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.
AB - PURPOSE Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement. METHODS Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed , 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer. RESULTS Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred fortytwo (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional MLH1 hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets. CONCLUSION UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.
UR - https://www.scopus.com/pages/publications/85109002956
U2 - 10.1200/PO.20.00525
DO - 10.1200/PO.20.00525
M3 - Article
AN - SCOPUS:85109002956
SN - 2473-4284
VL - 5
SP - 779
EP - 791
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -