Evidence map›Paper›PMID 26604137›Full record

ArticleHuman molecular genetics2016

Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.

Kristin A Rand, Nadin Rohland, Arti Tandon, Alex Stram, Xin Sheng, Ron Do, Bogdan Pasaniuc, Alex Allen, Dominique Quinque, Swapan Mallick and 11 more

Open access · bronzeAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020
    Pooled it
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  16. Inherited Predisposition to Prostate Cancer: From Gene Discovery to Clinical Impact.Transactions of the American Clinical and Climatological Association · 2017
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 8 institutions in 2 countries.

Kristin A RandDepartment of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
Nadin RohlandDepartment of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Arti TandonDepartment of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alex StramDepartment of Preventive Medicine, Keck School of Medicine.
Xin ShengDepartment of Preventive Medicine, Keck School of Medicine.
Ron DoDepartment of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bogdan PasaniucBioinformatics Interdepartmental Program, Department of Human Genetics, David Geffen School of Medicine, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Alex AllenDepartment of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Dominique QuinqueDepartment of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Swapan MallickDepartment of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Loic Le MarchandEpidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, HI 96813, USA.
Sam KaggwaDepartment of Surgery.
Alex LubwamaSchool of Public Health, Makerere University College of Health Sciences, Kampala, Uganda and.
African Ancestry Prostate Cancer GWAS Consortium
ELLIPSE/GAME-ON Consortium
Daniel O StramDepartment of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
Stephen WatyaSchool of Public Health, Makerere University College of Health Sciences, Kampala, Uganda and Uro Care, Kampala, Uganda.
Brian E HendersonDepartment of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
David V ContiDepartment of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
David ReichDepartment of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA, haiman@usc.edu.
Harvard University · USUniversity of Southern California · USKeck Graduate Institute · USMakerere University · UGBroad Institute · USCancer Center of Hawaii · USHoward Hughes Medical Institute · USUniversity of California, Los Angeles · US

Funding

SWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2M
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
SWOG NCORP Research BaseUG1CA189974 · NCI · THE HOPE FOUNDATION · PI CHARLES D. BLANKE, DAWN HERSHMAN · 2014 to 2026
$80.6M
Southern Community Cohort StudyR01CA092447 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLOT, WILLIAM J., ZHENG, WEI · 2001 to 2015
$74.0M
Understanding Population Differences in Cancer: The MEC StudyU01CA164973 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI HAIMAN, CHRISTOPHER ALAN, LE MARCHAND, LOIC · 2015 to 2025
$37.4M
GENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTSR01CA063464 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2001 to 2005
$23.2M
Multiethnic Cohort Study of Diet and CancerR37CA054281 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 2003 to 2012
$23.2M
CALIFORNIA'S PARTICIPATION IN THE NATIONAL CANCER PREVENTION AND CONTRO PROGRAMU58DP000807 · DP · PUBLIC HEALTH INSTITUTE · PI SNIPES, KURT P · 2007 to 2011
$22.5M
Pilot Project ProgramP30ES007784 · NIEHS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RICHIE, ELLEN R · 1996 to 2011
$16.4M
The Howard University SCORE Program Supplemental GrantS06GM008016 · NIGMS · HOWARD UNIVERSITY · PI ADEYEMO, ADEBOWALE A · 1989 to 2009
$16.1M
Understanding Ethnic Differences in Cancer: The Multiethnic Cohort StudyUM1CA164973 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI HENDERSON, BRIAN E, LE MARCHAND, LOIC · 2012 to 2014
$11.3M
Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3U01CA098758 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2003 to 2010
$11.0M
Cancer Research UK C5047/A8384Intramural NIH HHSNCCDPHP CDC HHS 1U58DP000807-3NCI NIH HHS CA056678NCI NIH HHS CA082664NCI NIH HHS CA092447NCI NIH HHS CA092579NCI NIH HHS CA127298NCI NIH HHS CA1326792NCI NIH HHS CA148085NCI NIH HHS CA148537NCI NIH HHS CA164973NCI NIH HHS CA37429NCI NIH HHS CA54281NCI NIH HHS CA63464NCI NIH HHS CA68485NCI NIH HHS CA68578NCI NIH HHS CA88164NCI NIH HHS R01 CA092447NCI NIH HHS R01 CA 165862NCI NIH HHS R01 CA165862NCI NIH HHS RC2 CA 148085NCI NIH HHS RC2 CA148085NCI NIH HHS U01 CA164973NCI NIH HHS U01-CA98216NCI NIH HHS U01-CA98233NCI NIH HHS U01-CA98710NCI NIH HHS U01-CA98758NCI NIH HHS U10 CA037429NCI NIH HHS UG1 CA189974NCI NIH HHS UM1 CA164973NCI NIH HHS UM1 CA182883NHGRI NIH HHS HG004726NIEHS NIH HHS ES007784NIEHS NIH HHS ES011126NIEHS NIH HHS R01 ES011126NIGMS NIH HHS S06GM08016
6 · The paper itself

Abstract

Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk.

Indexed as

Genetic Association StudiesGenetic Predisposition to DiseasePolymorphism, Single NucleotideSequence Analysis, DNAAdultAgedBlack or African AmericanBlack PeopleExomeHumansMaleMiddle AgedProstatic NeoplasmsRisk

Identifiers

PMID26604137
PMCPMC4865031
OpenAlexW2258353569

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.