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Record W3023665721 · doi:10.1016/j.eururo.2020.04.060

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

2020· article· en· W3023665721 on OpenAlexaff
Burcu F. Darst, Peggy Wan, Xin Sheng, Jeannette T. Bensen, Sue A. Ingles, Benjamin A. Rybicki, Barbara Nemesure, Esther M. John, Jay H. Fowke, Victoria L. Stevens, Sonja I. Berndt, Chad D. Huff, Sara S. Strom, Jong Y. Park, Wei Zheng, Elaine A. Ostrander, Patrick C. Walsh, Shiv Srivastava, John D. Carpten, Thomas A. Sellers, Kosj Yamoah, Adam B. Murphy, Maureen Sanderson, Dana C. Crawford, Susan M. Gapstur, William S. Bush, Melinda C. Aldrich, Olivier Cussenot, Meredith Yeager, György Petrovics, Jennifer Cullen, Christine Neslund‐Dudas, Rick A. Kittles, Jianfeng Xu, Mariana C. Stern, Zsofia Kote‐Jarai, Koveela Govindasami, Anand P. Chokkalingam, Luc Multigner, Marie‐Elise Parent, F. Ménégaux, Géraldine Cancel‐Tassin, Adam S. Kibel, Eric A. Klein, Phyllis J. Goodman, Bettina F. Drake, Jennifer J. Hu, Peter E. Clark, Pascal Blanchet, Graham Casey, Anselm Hennis, Alexander Lubwama, Ian M. Thompson, Robin J. Leach, Susan Gundell, Loreall Pooler, Lucy Xia, James L. Mohler, Elizabeth T. H. Fontham, Gary J. Smith, Jack A. Taylor, Rosalind A. Eeles, L. Brureau, Stephen J. Chanock, Stephen Watya, Janet L. Stanford, Diptasri Mandal, William B. Isaacs, Kathleen A. Cooney, William J. Blot, David V. Conti, Christopher A. Haiman

Bibliographic record

VenueEuropean Urology · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer-related molecular mechanisms research
Canadian institutionsInstitut National de la Recherche Scientifique
FundersNational Institute of Environmental Health SciencesNational Cancer InstituteAchievement Rewards for College Scientists Foundation
KeywordsMedicineGermlineProstate cancerGermline mutationCancerProstate diseaseOncologyProstateGynecologyGeneticsInternal medicineMutationGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.068
Threshold uncertainty score0.566

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.269
Teacher spread0.253 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations51
Published2020
Admission routes1
Has abstractyes

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