Frequency and face validity of reported family history of cancer in first-degree relatives and genetic syndromes among children with cancer in Project:EveryChild: A report from the Children’s Oncology Group

Fuentes Bolanos NA, Lupo PJ, Tucker KM, Hawkins DS, Porter CC, Villani A, Spector LG. Frequency and face validity of reported family history of cancer in first-degree relatives and genetic syndromes among children with cancer in Project:EveryChild: A report from the Children’s Oncology Group. Cancer. 2026 Jan 1;132(1):e70231. doi: 10.1002/cncr.70231. PMID: 41457435; PMCID: PMC13242624.

Taking a family history of cancer (FH) is essential for identifying individuals with heritable cancer predisposition. Project:EveryChild (APEC14B1), the registration and biobanking protocol of the Children’s Oncology Group (COG), includes suggested questions about FH in first-degree relatives and personal history of genetic syndromes (GS) in pediatric oncology patients. The validity of these items is unclear; therefore, we assessed the data quality and face validity of the responses. We analysed case report forms regarding FH and GS of 30,157 participants (birth to 21 years) with newly diagnosed pediatric cancer enrolled in APEC14B1. FH and GS data were manually curated to interpret the responses and group them into categories, followed by face validity assessment—defined as the extent to which the information provided represented what it was intended to capture. Responses were provided for 65.7% of participants (n=19,810), with 6.1% reporting FH (n=1,204). Of those, 97.9% (n=1,178) included sufficient free-text detail to assess face validity, though 49.4% required manual interpretation. Among FH reports, 48.3% (n=595) were suggestive of heritable cancer risk. GS was reported in 4.3% of responders (n=863), with 93.3% (n=780) showing face validity after curation. Down syndrome (n=302) and neurofibromatosis type 1 (NF1, n=93) were the most frequently reported syndromes, with NF1 most common in CNS tumor cases. Despite limitations and the need for manual curation, FH and GS data collected via proposed questions were sufficient to identify known heritable cancer patterns. These findings support questionnaire-based data collection and highlight areas for improvement.