Differences in Prostate Cancer Transcriptomes by Age at Diagnosis: Are Primary Tumors from Older Men Inherently Different?

Autor: Zhou CD; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Pettersson A; Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden., Plym A; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Urology, Brigham and Women's Hospital, Boston, Massachusetts., Tyekucheva S; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Penney KL; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Sesso HD; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Division of Preventative Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Kantoff PW; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Convergent Therapeutics Inc., Cambridge, Massachusetts., Mucci LA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Stopsack KH; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Jazyk: angličtina
Zdroj: Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2022 Dec 01; Vol. 15 (12), pp. 815-825.
DOI: 10.1158/1940-6207.CAPR-22-0212
Abstrakt: Older age at diagnosis is consistently associated with worse clinical outcomes in prostate cancer. We sought to characterize gene expression profiles of prostate tumor tissue by age at diagnosis. We conducted a discovery analysis in The Cancer Genome Atlas prostate cancer dataset (n = 320; 29% of men >65 years at diagnosis), using linear regressions of age at diagnosis and mRNA expression and adjusting for TMPRSS2:ERG fusion status and race. This analysis identified 13 age-related candidate genes at FDR < 0.1, six of which were also found in an analysis additionally adjusted for Gleason score. We then validated the 13 age-related genes in a transcriptome study nested in the Health Professionals Follow-up Study and Physicians' Health Study (n = 374; 53% of men >65 years). Gene expression differences by age in the 13 candidate genes were directionally consistent, and age at diagnosis was weakly associated with the 13-gene score. However, the age-related genes were not consistently associated with risk of metastases and prostate cancer-specific death. Collectively, these findings argue against tumor genomic differences as a main explanation for age-related differences in prostate cancer prognosis.
Prevention Relevance: Older age at diagnosis is consistently associated with worse clinical outcomes in prostate cancer. This study with independent discovery and validation sets and long-term follow-up suggests that prevention of lethal prostate cancer should focus on implementing appropriate screening, staging, and treatment among older men without expecting fundamentally different tumor biology.
(©2022 American Association for Cancer Research.)
Databáze: MEDLINE