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Journal Articles European Urology Year : 2020

A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry

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Jeannette T Bensen
  • Function : Author
Sue A Ingles
  • Function : Author
Benjamin A Rybicki
  • Function : Author
Barbara Nemesure
  • Function : Author
Esther M John
  • Function : Author
Jay H Fowke
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Victoria L Stevens
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Sonja I Berndt
  • Function : Author
Chad D Huff
  • Function : Author
Sara S Strom
  • Function : Author
Jong y Park
  • Function : Author
Wei Zheng
Elaine A Ostrander
  • Function : Author
Patrick C Walsh
  • Function : Author
Shiv Srivastava
  • Function : Author
John Carpten
  • Function : Author
Thomas A Sellers
  • Function : Author
Kosj Yamoah
  • Function : Author
Adam B Murphy
  • Function : Author
Maureen Sanderson
  • Function : Author
Dana C Crawford
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Susan M Gapstur
  • Function : Author
William S Bush
  • Function : Author
Melinda C Aldrich
  • Function : Author
Meredith Yeager
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Gyorgy Petrovics
  • Function : Author
Jennifer Cullen
  • Function : Author
Christine Neslund-Dudas
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Rick A Kittles
  • Function : Author
Jianfeng Xu
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Mariana C Stern
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Zsofia Kote-Jarai
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Koveela Govindasami
  • Function : Author
Anand P Chokkalingam
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Marie-Elise Parent
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Geraldine Cancel-Tassin
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Adam S Kibel
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Eric A Klein
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Phyllis J Goodman
  • Function : Author
Bettina F Drake
  • Function : Author
Jennifer J Hu
  • Function : Author
Peter E Clark
  • Function : Author
Graham Casey
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Anselm J M Hennis
  • Function : Author
Alexander Lubwama
  • Function : Author
Ian M Thompson Jr
  • Function : Author
Robin Leach
  • Function : Author
Susan M Gundell
  • Function : Author
Loreall Pooler
  • Function : Author
Lucy Xia
  • Function : Author
James L Mohler
  • Function : Author
Elizabeth T H Fontham
  • Function : Author
Gary J Smith
  • Function : Author
Jack A Taylor
  • Function : Author
Rosalind A Eeles
  • Function : Author
Laurent Brureau
  • Function : Author
Stephen J Chanock
  • Function : Author
Stephen Watya
  • Function : Author
Janet L Stanford
  • Function : Author
Diptasri Mandal
  • Function : Author
William B Isaacs
  • Function : Author
Kathleen Cooney
  • Function : Author
William J Blot
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Abstract

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.
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Dates and versions

hal-02860251 , version 1 (29-09-2020)

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Cite

Burcu F Darst, Peggy Wan, Xin Sheng, Jeannette T Bensen, Sue A Ingles, et al.. A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry. European Urology, 2020, 78 (3), pp.316-320. ⟨10.1016/j.eururo.2020.04.060⟩. ⟨hal-02860251⟩
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