Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review

Corso, Giovanni; Montagna, Giacomo; Figueiredo, Joana; Vecchia, Carlo La; Fumagalli, Uberto; Fernandes, Maria Sofia; Seixas, Susana; Roviello, Franco; Trovato, C.; Guerini-Rocco, Elena; Fusco, Nicola; Pravettoni, Gabriella; Petrocchi, Serena; Rotili, Anna; Massari, Giulia; Magnoni, Francesca; Lorenzi, Francesca De; Bottoni, Manuela; Galimberti, Viviana; Sanches, J. Miguel; Calvello, Mariarosaria; Seruca, Raquel; Bonanni, Bernardo

doi:10.3390/cancers12061598

Cited by 43 publications

(26 citation statements)

References 158 publications

(240 reference statements)

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“…Although environmental risk factors account for variations in incidence and mortality rates worldwide, family history is a major risk factor for gastric cancer [ 13 ]. A number of genetic loci have been associated with GC risk, which may directly impact disease progression or interact with environmental factors in the causal pathway [ 1 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review

Corso

Bellerba

et al. 2021

Cancers

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Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by CDH1 germline mutations. Nevertheless, current CDH1 genetic screening recommendations disregard an unbalanced worldwide distribution of CDH1 variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing CDH1 variants in gastric cancer patients originating from both high- and low-prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that CDH1 mutations are more frequently identified in gastric cancer low-incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of CDH1 alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high-incidence areas of gastric cancer, when compared with non-missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of CDH1 variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for CDH1 genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease.

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Section: Introductionmentioning

confidence: 99%

Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review

Corso

Bellerba

et al. 2021

Cancers

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“…With the widespread introduction of MultiGene Panel Testing (MGPT) in clinical practice, we are observing an increased rate of CDH1 germline mutations in apparently healthy individuals and without any correlation with the classic HDGC syndrome [ 8 ]. The identification of unexpected CDH1 germline mutations in the absence of specific clinical criteria suggests that HDGC syndrome may be a more complex syndrome than the one originally defined [ 9 ]. A cross-sectional prevalence study from the University of Southern California, Los Angeles, included all patients who underwent MGPT between 2012–2014.…”

Section: Future Perspectivesmentioning

confidence: 99%

E-Cadherin (CDH1 Gene) Germline Mutations in Gastric Cancer: Evolutions and Innovations

Corso

Bonanni

2020

Cancers

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“…[4] Lifetime BC risks associated with other BC predisposition genes vary from at least a 4-fold increase for the high-risk genes (CDH1, PALB2, PTEN, STK11, and TP53) to a 2-to 3-fold increase for the moderate-risk genes (ATM, CHEK2, NBN, and NF1). [4][5][6][7][8][9][10][11][12] Breast cancer associated with a hereditary predisposition may also be diagnosed at earlier ages; in particular, women with BRCA1/2 or TP53 PVs are often diagnosed with premenopausal BC. [4,13] Contralateral BC risks are influenced by multiple factors, including age at first BC diagnosis, family history of BC, previous treatments, and underlying genetic predisposition.…”

Section: Introductionmentioning

confidence: 99%

Timely Cancer Genetic Counseling and Testing for Young Women With Breast Cancer: Impact on Surgical Decision-making for Contralateral Risk-reducing Mastectomy

Dettwyler

Thull

McAuliffe

et al. 2022

Preprint

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PURPOSE: Genetic testing (GT) can identify individuals with pathogenic variants (PV) in breast cancer (BC) predisposition genes, who may consider contralateral risk-reducing mastectomy (CRRM). We report on CRRM rates in young women newly diagnosed with BC who received GT through a multidisciplinary clinic. METHODS: Clinical data was reviewed for patients seen between November 2014 and June 2019. Patients with non-metastatic, unilateral BC diagnosed at age ≤45 and completed GT prior to surgery were included. Associations between surgical intervention and age, BC stage, family history, and GT results were evaluated. RESULTS: Of the 194 patients, 30 (15.5%) had a PV in a BC predisposition gene (ATM , BRCA1, BRCA2, CHEK2, NBN, NF1), with 66.7% in BRCA1 or BRCA2. Of 164 (84.5%) uninformative results, 132 (68%) were negative and 32 (16.5%) were variants of uncertain significance (VUS). Overall, 67 (34.5%) had CRRM, including 25/30 (83.3%) PV carriers and 42/164 (25.6%) non-carriers. Only a positive test result was associated with CRRM (p < 0.01). For the 164 with uninformative results, CRRM was not associated with age (p = 0.23), a VUS, (p = 0.08), family history (p = 0.19), or BC stage (p = 0.10). CONCLUSION: In this cohort of young women with BC, the identification of a PV in a BC predisposition gene was the only factor associated with the decision to pursue CRRM. Thus, incorporation of genetic services in the initial evaluation of young patients with a new BC could contribute to the surgical decision-making process.

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Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review

Cited by 43 publications

References 158 publications

Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review

Geographical Distribution of E-cadherin Germline Mutations in the Context of Diffuse Gastric Cancer: A Systematic Review

E-Cadherin (CDH1 Gene) Germline Mutations in Gastric Cancer: Evolutions and Innovations

Timely Cancer Genetic Counseling and Testing for Young Women With Breast Cancer: Impact on Surgical Decision-making for Contralateral Risk-reducing Mastectomy

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