Association Between Hereditary Lobular Breast Cancer Due to <i>CDH1</i> Variants and Gastric Cancer Risk

Gamble, Lauren A.; Rossi, Antonello; Fasaye, Grace‐Ann; Kesserwan, Chimene; Hernandez, Jonathan M.; Blakely, Andrew M.; Davis, Jeremy L.

doi:10.1001/jamasurg.2021.5118

Cited by 19 publications

(30 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CDH1 is essential in the maintenance of cell morphology and regulation of cell adhesion (14). CDH1 gene encodes E-cadherin (E-cad), which participates in the inhibition of migration and invasion of tumor cells (15). Interestingly, our study did not observe any relationship between the CDH1 methylation and GC Lauren classification, which merits further investigation.…”

Section: Discussionmentioning

confidence: 50%

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis

Ma¹,

Wang²,

Pu³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: Although multiple gene promoter hypermethylation has been associated with gastric carcinogenesis, data on their specific relationship remains scant. We aimed to investigate the correlation between the status of multiple gene promoter methylation and gastric cancer (GC).Methods: We searched Pubmed, EMBASE, CNKI, Wanfang, Cqvip and Cochrane Library up to May 2021. We systematically assessed the association between methylation status of the CpG islands and the risk of GC. We compared the incidence of DNA methylation between tumor and non-tumor tissues, and evaluated the clinicopathological significance of the DNA methylation in gastric carcinoma. The data was presented by an odds ratio (OR) with an accompanying 95% confidence interval (CI). We then generated forest plots calculated by fixed-effects or random-effects model.Results: This study enrolled a total of 201 studies (140 papers). Our analysis showed a higher frequency of methylation of the CpG islands in GC tissues compared to non-neoplastic tissues. Besides, the data demonstrated that polygene's aberrant promoter methylation might be linked to the initial development and progression of GC.Discussion: The genes with altered DNA methylation might serve as epigenetic biomarkers, providing a promising molecular diagnostic and prognostic tool for human GC. However, our findings need further evaluation in large randomized controlled trials.

show abstract

Section: Discussionmentioning

confidence: 50%

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis

Ma¹,

Wang²,

Pu³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…Mutation rate detection in LBC is increasing 22,30,32 . It is interesting to note that the majority of the screened LBC families were not associated with the DGC spectrum.…”

Section: Lobular Breast Cancermentioning

confidence: 94%

“…Individuals with germline CDH1 non‐truncating mutations 29 and without a clear family history of GC seem to be associated with a lower penetrance of GC risk. Although some Authors stress to perform PTG also in germline CDH1 pathogenic mutation carriers with unclear family history for GC, 30 PTG should be considered only in case of a clear HDGC phenotype with a documented germline CDH1 pathogenic variant. Individuals with variants of unknown significance (VUS), and without a clear family history of GC are not eligible for PTG 4,31 …”

Section: Diffuse Gastric Cancermentioning

confidence: 99%

“…It has been postulated that in absence of family history for GC, in germline CDH1 mutation carriers GC risk could appear lower. Interestingly, very recently, Gamble et al identified occult gastric carcinoma in specimens from PTGs performed on HLBC patients 30 . When testing for CDH1 mutations, the authors did not adopt the specific clinical criteria established for the HLBC syndrome, including 44 LBC patients with just a positive family history of BC.…”

Section: Lobular Breast Cancermentioning

confidence: 99%

“…Mutation rate detection in LBC is increasing. 22,30,32 It is interesting to note that the majority of the screened LBC families were not associated with the DGC spectrum. The exact GC risk in HLBC, and, In the case of mixed HDGC syndrome, the risk of BC for females is 42% (95% CI, 23%-68%), in accord with the IGCLC criteria.…”

Section: Penetrance Riskmentioning

confidence: 99%

See 2 more Smart Citations

Pleiotropic cancer manifestations of germline CDH1 mutations: Risks and management

Corso

2022

Journal of Surgical Oncology

View full text Add to dashboard Cite

Germline CDH1 defects are related with the development of multiple cancers due its pleiotropic nature. These several conditions are associated with various risks of penetrance and with different clinical management strategies. In this clinical review, we described the penetrance risks of gastric, breast, prostate, and colorectal cancers, in CDH1 carriers, within as well as outside the familial setting, and the best approaches to manage each risk, using either prophylactic surgery or surveillance.

show abstract

Germline CDH1 Variants and Lifetime Cancer Risk

Ryan,

Fasaye,

Gallanis

et al. 2024

JAMA

View full text Add to dashboard Cite

ImportanceApproximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants.ObjectiveTo describe gastric and breast cancer risk estimates for individuals with CDH1 variants.Design, Setting, and ParticipantsMulticenter, retrospective cohort and modeling study of 213 families from North America with a CDH1 pathogenic or likely pathogenic (P/LP) variant in 1 or more family members conducted between January 2021 and August 2022.Main Outcomes and MeasuresHazard ratios (HRs), defined as risk in variant carriers relative to noncarriers, were estimated for each cancer type and used to calculate cumulative risks and risks per decade of life up to age 80 years.ResultsA total of 7323 individuals from 213 families were studied, including 883 with a CDH1 P/LP variant (median proband age, 53 years [IQR, 42-62]; 4% Asian; 4% Hispanic; 85% non-Hispanic White; 50% female). In individuals with a CDH1 P/LP variant, the prevalence of gastric cancer was 13.9% (123/883) and the prevalence of breast cancer among female carriers was 26.3% (144/547). The estimated HR for advanced gastric cancer was 33.5 (95% CI, 9.8-112) at age 30 years and 3.5 (95% CI, 0.4-30.3) at age 70 years. The lifetime cumulative risk of advanced gastric cancer in male and female carriers was 10.3% (95% CI, 6%-23.6%) and 6.5% (95% CI, 3.8%-15.1%), respectively. Gastric cancer risk estimates based on family history indicated that a carrier with 3 affected first-degree relatives had a penetrance of approximately 38% (95% CI, 25%-64%). The HR for breast cancer among female carriers was 5.7 (95% CI, 2.5-13.2) at age 30 years and 3.9 (95% CI, 1.1-13.7) at age 70 years. The lifetime cumulative risk of breast cancer among female carriers was 36.8% (95% CI, 25.7%-62.9%).Conclusions and RelevanceAmong families from North America with germline CDH1 P/LP variants, the cumulative risk of gastric cancer was 7% to 10%, which was lower than previously described, and the cumulative risk of breast cancer among female carriers was 37%, which was similar to prior estimates. These findings inform current management of individuals with germline CDH1 variants.

show abstract

Association Between Hereditary Lobular Breast Cancer Due to CDH1 Variants and Gastric Cancer Risk

Cited by 19 publications

References 12 publications

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis

Pleiotropic cancer manifestations of germline CDH1 mutations: Risks and management

Germline CDH1 Variants and Lifetime Cancer Risk

Contact Info

Product

Resources

About