Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status
Hereditary diffuse gastric cancer (HDGC) is an inherited cancer susceptibility syndrome characterized by an elevated risk for diffuse gastric cancer (DGC) and lobular breast cancer (LBC). Some patients fulfilling the clinical testing criteria harbor a pathogenic <i>CDH1</i> or <i>C...
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MDPI AG
2020-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/12/3726 |
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| author | Tim Marwitz Robert Hüneburg Isabel Spier Jan-Frederic Lau Glen Kristiansen Philipp Lingohr Jörg C. Kalff Stefan Aretz Jacob Nattermann Christian P. Strassburg |
| author_facet | Tim Marwitz Robert Hüneburg Isabel Spier Jan-Frederic Lau Glen Kristiansen Philipp Lingohr Jörg C. Kalff Stefan Aretz Jacob Nattermann Christian P. Strassburg |
| author_sort | Tim Marwitz |
| collection | DOAJ |
| description | Hereditary diffuse gastric cancer (HDGC) is an inherited cancer susceptibility syndrome characterized by an elevated risk for diffuse gastric cancer (DGC) and lobular breast cancer (LBC). Some patients fulfilling the clinical testing criteria harbor a pathogenic <i>CDH1</i> or <i>CTNNA1</i> germline variant. However, the underlying mechanism for around 80% of the patients with a family or personal history of DGC and LBC has so far not been elucidated. In this cohort study, patients meeting the 2015 HDGC clinical testing criteria were included, and subsequently, <i>CDH1</i> sequencing was performed. Of the 207 patients (161 families) in this study, we detected 21 pathogenic or likely pathogenic <i>CDH1</i> variants (PV) in 60 patients (28 families) and one <i>CTNNA1</i> PV in two patients from one family. Sixty-eight percent (<i>n</i> = 141) of patients were female. The overall PV detection rate was 18% (29/161 families). Criterion 1 and 3 of the 2015 HDGC testing criteria yielded the highest detection rate of <i>CDH1/CTNNA1</i> PVs (21% and 28%). PV carriers and patients without proven PV were compared. Risk of gastric cancer (GC) (38/62 61% vs. 102/140 73%) and age at diagnosis (40 ± 13 years vs. 44 ± 12 years) were similar between the two groups. However, GC was more advanced in gastrectomy specimens of patients without PV (81% vs. 26%). LBC prevalence in female carriers of a PV was 20% (<i>n</i> = 8/40). Clinical phenotypes differed strongly between families with the same PV. Emphasis should be on detecting more causative genes predisposing for HDGC and improve the management of patients without a proven pathogenic germline variant. |
| first_indexed | 2024-03-10T14:09:08Z |
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| id | doaj.art-baa5fa0e71824edea3291e7f76a74dc1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:09:08Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-baa5fa0e71824edea3291e7f76a74dc12023-11-21T00:26:09ZengMDPI AGCancers2072-66942020-12-011212372610.3390/cancers12123726Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant StatusTim Marwitz0Robert Hüneburg1Isabel Spier2Jan-Frederic Lau3Glen Kristiansen4Philipp Lingohr5Jörg C. Kalff6Stefan Aretz7Jacob Nattermann8Christian P. Strassburg9Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Internal Medicine I, University Hospital Bonn, 53127 Bonn, GermanyNational Center for Hereditary Tumor Syndromes, University Hospital Bonn, 53127 Bonn, GermanyNational Center for Hereditary Tumor Syndromes, University Hospital Bonn, 53127 Bonn, GermanyNational Center for Hereditary Tumor Syndromes, University Hospital Bonn, 53127 Bonn, GermanyNational Center for Hereditary Tumor Syndromes, University Hospital Bonn, 53127 Bonn, GermanyNational Center for Hereditary Tumor Syndromes, University Hospital Bonn, 53127 Bonn, GermanyNational Center for Hereditary Tumor Syndromes, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Internal Medicine I, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Internal Medicine I, University Hospital Bonn, 53127 Bonn, GermanyHereditary diffuse gastric cancer (HDGC) is an inherited cancer susceptibility syndrome characterized by an elevated risk for diffuse gastric cancer (DGC) and lobular breast cancer (LBC). Some patients fulfilling the clinical testing criteria harbor a pathogenic <i>CDH1</i> or <i>CTNNA1</i> germline variant. However, the underlying mechanism for around 80% of the patients with a family or personal history of DGC and LBC has so far not been elucidated. In this cohort study, patients meeting the 2015 HDGC clinical testing criteria were included, and subsequently, <i>CDH1</i> sequencing was performed. Of the 207 patients (161 families) in this study, we detected 21 pathogenic or likely pathogenic <i>CDH1</i> variants (PV) in 60 patients (28 families) and one <i>CTNNA1</i> PV in two patients from one family. Sixty-eight percent (<i>n</i> = 141) of patients were female. The overall PV detection rate was 18% (29/161 families). Criterion 1 and 3 of the 2015 HDGC testing criteria yielded the highest detection rate of <i>CDH1/CTNNA1</i> PVs (21% and 28%). PV carriers and patients without proven PV were compared. Risk of gastric cancer (GC) (38/62 61% vs. 102/140 73%) and age at diagnosis (40 ± 13 years vs. 44 ± 12 years) were similar between the two groups. However, GC was more advanced in gastrectomy specimens of patients without PV (81% vs. 26%). LBC prevalence in female carriers of a PV was 20% (<i>n</i> = 8/40). Clinical phenotypes differed strongly between families with the same PV. Emphasis should be on detecting more causative genes predisposing for HDGC and improve the management of patients without a proven pathogenic germline variant.https://www.mdpi.com/2072-6694/12/12/3726hereditary cancergastric cancer<i>CDH1</i><i>CTNNA1</i>HDGC |
| spellingShingle | Tim Marwitz Robert Hüneburg Isabel Spier Jan-Frederic Lau Glen Kristiansen Philipp Lingohr Jörg C. Kalff Stefan Aretz Jacob Nattermann Christian P. Strassburg Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status Cancers hereditary cancer gastric cancer <i>CDH1</i> <i>CTNNA1</i> HDGC |
| title | Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status |
| title_full | Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status |
| title_fullStr | Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status |
| title_full_unstemmed | Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status |
| title_short | Hereditary Diffuse Gastric Cancer: A Comparative Cohort Study According to Pathogenic Variant Status |
| title_sort | hereditary diffuse gastric cancer a comparative cohort study according to pathogenic variant status |
| topic | hereditary cancer gastric cancer <i>CDH1</i> <i>CTNNA1</i> HDGC |
| url | https://www.mdpi.com/2072-6694/12/12/3726 |
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