Lepage Mathis, Uhrhammer Nancy, Privat Maud, Ponelle-Chachuat Flora, Kossai Myriam, Scanzi Julien, Ouedraogo Zangbéwendé Guy, Gay-Bellile Mathilde, Bidet Yannick, Cavaillé Mathias
Département d'Oncogénétique, Centre Jean Perrin, 63011 Clermont-Ferrand, France.
INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Université Clermont Auvergne, 63000 Clermont-Ferrand, France.
Genes (Basel). 2023 Aug 25;14(9):1677. doi: 10.3390/genes14091677.
Germline pathogenic variants in E-cadherin () confer high risk of developing lobular breast cancer and diffuse gastric cancer (DGC). The cumulative risk of DGC in carriers has been recently reassessed (from 40-83% by age 80 to 25-42%) and varies according to the presence and number of gastric cancers in the family. As there is no accurate estimate of the risk of gastric cancer in families without DGC, the International Gastric Cancer Linkage Consortium recommendation is not straightforward: prophylactic gastrectomy or endoscopic surveillance should be proposed for these families. The inclusion of in constitutional gene panels for hereditary breast and ovarian cancer and for gastrointestinal cancers, recommended by the French Genetic and Cancer Consortium in 2018 and 2020, leads to the identification of families with lobular cancer without DGC but also to incidental findings of pathogenic variants. Management of carriers in case of incidental findings is complex and causes dilemmas for both patients and providers. We report eleven families (47 carriers) from our oncogenetic department specialized in breast and ovarian cancer, including four incidental findings. We confirmed that six families did not have diffuse gastric cancer in their medical records. We discuss the management of the risk of diffuse gastric cancer in Hereditary Lobular Breast Cancer (HLBC) through a family of 11 carriers where foci were identified in endoscopic surveillance. We also report a new colon signet ring cancer case in a carrier, a rare aggressive cancer included in -related malignancies.
E-钙黏蛋白()的种系致病性变异会增加患小叶性乳腺癌和弥漫性胃癌(DGC)的风险。最近对携带该变异者患DGC的累积风险进行了重新评估(从80岁时的40%-83%降至25%-42%),且该风险因家族中胃癌的存在情况和数量而异。由于对于无DGC家族中患胃癌风险没有准确估计,国际胃癌连锁联盟的建议并不简单直接:对于这些家族应建议进行预防性胃切除术或内镜监测。法国遗传与癌症联盟在2018年和2020年推荐将该变异纳入遗传性乳腺癌和卵巢癌以及胃肠道癌的体质基因检测板中,这不仅能识别出无DGC的小叶癌家族,还能发现致病性变异的偶然发现。偶然发现情况下对携带该变异者的管理很复杂,给患者和医疗服务提供者都带来了困境。我们报告了来自我们专门诊治乳腺癌和卵巢癌的肿瘤遗传学部门的11个家族(47名携带该变异者),其中包括4例偶然发现。我们确认6个家族的病历中没有弥漫性胃癌。我们通过一个有11名携带该变异者的家族讨论了遗传性小叶性乳腺癌(HLBC)中弥漫性胃癌风险的管理,该家族在内镜监测中发现了病灶。我们还报告了1例携带该变异者患结肠印戒细胞癌的新病例,这是一种罕见的侵袭性癌症,属于与该变异相关的恶性肿瘤。
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