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Association between hereditary lobular breast cancer due to CDH1 variants and gastric cancer risk

JAMA Oct 18, 2021

Gamble LA, Rossi A, Fasaye GA, et al. - Findings showed high rates of occult signet ring cell gastric cancer in carriers of CDH1 pathogenic or likely pathogenic (P/LP) variants with no family history of gastric cancer. Regardless of family history, germline CDH1 P/LP variants seemed to have a highly penetrant gastric phenotype.

  • This is a cohort study of 283 patients with hereditary lobular breast cancer (HLBC) due to CDH1 P/LP variants.

  • Based on family history of breast and/or gastric cancer, patients were divided as: HLBC (15.5%), hereditary diffuse gastric cancer (HDGC) (16.2%), and mixed (68.2%).

  • There were 31 distinct families with 19 CDH1 variants in the HLBC group, 10 of those variants were also evident in the HDGC and mixed groups (52.6%).

  • Presence of occult signet ring cell gastric adenocarcinoma was evident in nearly all HLBC patients (93.8% [15 of 16 variants]) who elected for risk-reducing total gastrectomy due to their underlying CDH1 P/LP variant.

  • Among asymptomatic patients in the HDGC group, similar prevalence of occult gastric cancer was observed (94.7% [18 of 19 of variants]).

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