{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:29:46Z","timestamp":1788236986757,"version":"build-2803163510"},"reference-count":42,"publisher":"BMJ","issue":"10","funder":[{"name":"Intramural Research Program of the National Institutes of Health, National Cancer Institute","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,6,6]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diagnosis of a hereditary cancer syndrome may impact family planning, particularly in reproductive age individuals. Factors influencing reproductive decision-making are understudied in individuals with germline <jats:italic>CDH1<\/jats:italic> pathogenic or likely pathogenic (P\/LP) variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We characterised reproductive decision-making and perinatal outcomes in 121 individuals aged 18\u201349 with hereditary diffuse gastric and lobular breast cancer syndrome due to a germline <jats:italic>CDH1<\/jats:italic> P\/LP variant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Half of individuals (50%, 60\/121) reported their <jats:italic>CDH1<\/jats:italic> diagnosis impacted family planning. Psychosocial and economic barriers to reproduction were encountered by 47% (56\/119) of patients. Additionally, 12% (15\/121) of individuals delayed pregnancy to prioritise personal cancer risk management with either endoscopic surveillance, prophylactic total gastrectomy (PTG) or mastectomy. Women were more likely to experience guilt about passing their <jats:italic>CDH1<\/jats:italic> variant to offspring compared with men. Perinatal and fetal outcomes were investigated in six women who gave birth at a median time of 24 months (IQR 20\u201344) after PTG. Maternal micronutrient deficiencies were not uncommon in pregnant women after PTG despite compliance with a bariatric, prenatal multivitamin. Majority of women who became pregnant after PTG reported worsening post-gastrectomy syndromes. Most infants (90%, 9\/10) born after PTG were full-term and no fetal complications were reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Reproductive decision-making is complex in individuals with germline <jats:italic>CDH1<\/jats:italic> variants, who often encounter psychosocial and physical challenges during family planning and pregnancy. However, successful pregnancy is possible after PTG with the guidance of a multidisciplinary team including maternal fetal medicine specialists and a registered dietitian.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03030404\">NCT03030404<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2025-110857","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T13:21:04Z","timestamp":1750425664000},"page":"609-616","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Reproductive decision-making and pregnancy in germline <i>CDH1<\/i> variant carriers"],"prefix":"10.1136","volume":"62","clinical-trial-number":[{"clinical-trial-number":"nct03030404","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03030404","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03030404","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0194-5375","authenticated-orcid":false,"given":"Amber Famiglietti","family":"Gallanis","sequence":"first","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassidy","family":"Bowden","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Lopez","sequence":"additional","affiliation":[{"name":"Nutrition Department, National Institutes of Health Clinical Center, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Turner","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace-Ann","family":"Fasaye","sequence":"additional","affiliation":[{"name":"Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi Reddy","family":"Perati","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Blakely","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6334-6936","authenticated-orcid":false,"given":"Jeremy L","family":"Davis","sequence":"additional","affiliation":[{"name":"Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA"},{"name":"Division of Surgical Oncology, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"2025100511174387000_62.10.609.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-070119-114727"},{"key":"2025100511174387000_62.10.609.2","doi-asserted-by":"publisher","DOI":"10.1038\/32918"},{"key":"2025100511174387000_62.10.609.3","doi-asserted-by":"crossref","first-page":"4313","DOI":"10.3390\/cancers15174313","article-title":"Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer","volume":"15","author":"Guerra","year":"2023","journal-title":"Cancers (Basel)"},{"key":"2025100511174387000_62.10.609.4","unstructured":"Ryan CE , Fasaye G-A , Gallanis AF , et al . Penetrance of Germline CDH1 Variants With Implications For Management: A North American Cohort Study. JAMA 2024."},{"key":"2025100511174387000_62.10.609.5","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1001\/jamaoncol.2019.1208","article-title":"Comparison of CDH1 Penetrance Estimates in Clinically Ascertained Families vs Families Ascertained for Multiple Gastric Cancers","volume":"5","author":"Roberts","year":"2019","journal-title":"JAMA Oncol"},{"key":"2025100511174387000_62.10.609.6","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30219-9"},{"key":"2025100511174387000_62.10.609.7","unstructured":"Network NCC . NCCN clinical practice guidelines in oncology (NCCN guidelines): gastric cancer. 2024. 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