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Impact of Family History and Germline Genetic Risk Single Nucleotide Polymorphisms on Long-Term Outcomes of Favorable-Risk Prostate Cancer.
Rumpf, Florian; Plym, Anna; Vaselkiv, Jane B; Penney, Kathryn L; Preston, Mark A; Kibel, Adam S; Mucci, Lorelei A; Salari, Keyan.
Afiliação
  • Rumpf F; Department of Urology, Massachusetts General Hospital, Boston, Massachusetts.
  • Plym A; Department of Anesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.
  • Vaselkiv JB; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • Penney KL; Division of Urology, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
  • Preston MA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Kibel AS; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • Mucci LA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
  • Salari K; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
J Urol ; 211(6): 754-764, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38598641
ABSTRACT

PURPOSE:

Family history and germline genetic risk single nucleotide polymorphisms (SNPs) have been separately shown to stratify lifetime risk of prostate cancer. Here, we evaluate the combined prognostic value of family history of prostate and other related cancers and germline risk SNPs among patients with favorable-risk prostate cancer. MATERIALS AND

METHODS:

A total of 1367 participants from the prospective Health Professionals Follow-up Study diagnosed with low- or favorable intermediate-risk prostate cancer from 1986 to 2017 underwent genome-wide SNP genotyping. Multivariable Cox regression was used to estimate the association between family history, specific germline risk variants, and a 269 SNP polygenic risk score with prostate cancer‒specific death.

RESULTS:

Family history of prostate, breast, and/or pancreatic cancer was observed in 489 (36%) participants. With median follow-up from diagnosis of 14.9 years, participants with favorable-risk prostate cancer with a positive family history had a significantly higher risk of prostate cancer‒specific death (HR 1.95, 95% CI 1.15-3.32, P = .014) compared to those without any family history. The rs2735839 (19q13) risk allele was associated with prostate cancer‒specific death (HR 1.81 per risk allele, 95% CI 1.04-3.17, P = .037), whereas the polygenic risk score was not. Combined family history and rs2735839 risk allele were each associated with an additive risk of prostate cancer‒specific death (HR 1.78 per risk factor, 95% CI 1.25-2.53, P = .001).

CONCLUSIONS:

Family history of prostate, breast, or pancreatic cancer and/or a 19q13 germline risk allele are associated with an elevated risk of prostate cancer‒specific death among favorable-risk patients. These findings have implications for how family history and germline genetic risk SNPs should be factored into clinical decision-making around favorable-risk prostate cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Mutação em Linhagem Germinativa / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único Limite: Aged / Humans / Male / Middle aged Idioma: En Revista: J Urol / J. urol. (Baltimore) / Journal of urology Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Mutação em Linhagem Germinativa / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único Limite: Aged / Humans / Male / Middle aged Idioma: En Revista: J Urol / J. urol. (Baltimore) / Journal of urology Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos