TY - JOUR
T1 - CDH1 germline variants are enriched in patients with colorectal cancer, gastric cancer, and breast cancer
AU - Adib, Elio
AU - El Zarif, Talal
AU - Nassar, Amin H.
AU - Akl, Elie W.
AU - Abou Alaiwi, Sarah
AU - Mouhieddine, Tarek H.
AU - Esplin, Edward D.
AU - Hatchell, Kathryn
AU - Nielsen, Sarah M.
AU - Rana, Huma Q.
AU - Choueiri, Toni K.
AU - Kwiatkowski, David J.
AU - Sonpavde, Guru
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2022/3/23
Y1 - 2022/3/23
N2 - Background and aims: CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities. Methods: We evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3). Results: CDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3. Conclusion: We report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings.
AB - Background and aims: CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities. Methods: We evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3). Results: CDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3. Conclusion: We report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings.
UR - http://www.scopus.com/inward/record.url?scp=85121584725&partnerID=8YFLogxK
U2 - 10.1038/s41416-021-01673-7
DO - 10.1038/s41416-021-01673-7
M3 - Article
C2 - 34949788
AN - SCOPUS:85121584725
SN - 0007-0920
VL - 126
SP - 797
EP - 803
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -