Beyond First-Degree Relatives: Unlocking the Genetic Insights from Extended Family History

Abstract

In oncology, a thorough family history is a cornerstone of genetic risk assessment, yet it is often limited to first-degree relatives—parents, siblings, and children—thereby missing crucial hereditary patterns. This article highlights the importance of including extended family members, such as second- and third-degree relatives, in risk assessment to uncover hereditary cancer syndromes that might otherwise go undetected. This case exemplifies how extended family history can transform patient care by enabling accurate diagnoses, personalized treatment, and preventive strategies. Despite time constraints in clinical settings, tools such as targeted questioning, standardized questionnaires, and digital pedigree platforms can streamline the collection of a three-generation pedigree. Current guidelines from the American College of Medical Genetics and Genomics and National Comprehensive Cancer Network recommend such comprehensive histories, underscoring their clinical value. Incorporating extended family history should become standard practice in oncology to align with the principles of precision medicine and improve outcomes for patients and their families.

Keywords

genetic screening - extended family history - oncology - precision medicine - hereditary cancer syndromes - three-generation pedigree

Authors' Contributions

Study conception and design: A.R. and R.S. Manuscript writing: A.R. and A.K. Critical review of manuscript: A.K. and R.S. Approval of final article: All authors. Accountability for all aspects of the work: All authors.

Patient Consent

Patient consent is not applicable as no patient data, clinical details, or identifiable information are included in this report.

Publication History

Article published online:
25 September 2025

• References

• 1 Guttmacher AE, Collins FS, Carmona RH. The family history--more important than ever. N Engl J Med 2004; 351 (22) 2333-2336
• 2 Wattendorf DJ, Hadley DW. Family history: the three-generation pedigree. Am Fam Physician 2005; 72 (03) 441-448
• 3 Holter S, Hall MJ, Hampel H. et al. Risk assessment and genetic counseling for Lynch syndrome - practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer. J Genet Couns 2022; 31 (03) 568-583
• 4 Daly MB, Pal T, Berry MP. et al; CGC, CGC, LCGC, CGC, CGC. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2021; 19 (01) 77-102
• 5 Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL. Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med 2015; 17 (01) 70-87
• 6 National Comprehensive Cancer Network. . NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2. 2024 ; and Colorectal, Version 1. 2023. Accessed 2025 at: https://www.nccn.org
• 7 Qureshi N, Carroll JC, Wilson B. et al. The current state of cancer family history collection tools in primary care: a systematic review. Genet Med 2009; 11 (07) 495-506
• 8 Bucheit L, Johansen Taber K, Ready K. Validation of a digital identification tool for individuals at risk for hereditary cancer syndromes. Hered Cancer Clin Pract 2019; 17: 2