Abstract Taller height has been associated with increased risk of incident and fatal prostate cancer, potentially through hormonal and growth factor activity during early life. We investigated this association by integrating early-life diet, germline genetics, and tumor biology. We included 49,370 men in the Health Professionals Follow-up Study who were cancer-free at study enrollment in 1986 and were followed through 2020. Cox models with age as the time scale estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for height and total and fatal prostate cancer, adjusting for demographics, BMI, smoking, and PSA screening. To decompose height into its determinants, we derived two residual height measures: genetic residual height from regressing observed height on the height polygenic risk score, and dietary residual height from regressing height on teenage dairy intake to isolate early-life dietary influences. To assess prostate tissue-specific effects of height, transcriptomic profiling was performed on prostate tumor (n = 418) and adjacent normal tissue (n = 209) using Affymetrix GeneChip arrays, and on stromal tissue (n = 272 tumor-adjacent, n = 120 tumor-distant) using RNA sequencing. Differential gene expression was analyzed with limma, and pathway enrichment with CAMERA using Gene Ontology Biological Process annotations. At enrollment, median age was 54 years (IQR 46-62) and median height was 70 inches (IQR 68-72). Over a median of 28 years of follow-up, 8326 prostate cancer cases were diagnosed, including 1189 fatal cases. Taller height was associated with increased risk of fatal (HR per 5 cm: 1.06, 95% CI 1.01-1.11) but not total prostate cancer (HR 1.00, 95% CI 0.98-1.01). The association for genetic residual height with fatal disease was null (HR ≈ 1), suggesting germline genetics largely explains the observed association. Associations using dietary residual height were similar to those for observed height, indicating minimal contribution from early-life diet. Transcriptomic analysis identified 82 height-associated pathways in tumor and 77 in adjacent normal tissue (FDR 0.05), with top pathways enriched for mRNA splicing regulation and fatty acid metabolism. In stromal tissue, 63 and 15 pathways were identified in tumor-adjacent and tumor-distant stroma, enriched for cytoplasmic translation and sensory perception/stimuli detection. Taller height was associated with increased risk of fatal prostate cancer during up to 34 years of follow-up. The attenuated association after accounting for genetic determinants of height suggests shared genetics between height and prostate cancer, while early-life dairy intake showed minimal impact. Transcriptomic evidence revealed differentially enriched pathways in the tumor and stroma, suggesting potential height-associated downstream biological processes in prostate cancer development. Citation Format: Anqi Wang, McKayla J. Ro, Megan R. Shanahan, Dian Fu, Hannah E. Guard, Jane Bailey Vaselkiv, Stephanie A. Smith-Warner, Konrad H. Stopsack, Devin Baynes, Massimo Loda, Andreas Pettersson, Edward L. Giovannucci, Siobhan Sutcliffe, Svitlana Tyekucheva, Burcu F. Darst, Lorelei A. Mucci. Adult height and prostate cancer in the Health Professionals Follow-Up Study: Integrating epidemiologic, genetic, and transcriptomic evidence abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6812.
Wang et al. (Fri,) studied this question.