Evidence map›Paper›PMID 33213418›Full record

ArticleBMC medical genetics2020

Mediation by differential DNA methylation of known associations between single nucleotide polymorphisms and bladder cancer risk.

Kristina M Jordahl, Amanda I Phipps, Timothy W Randolph, Lesley F Tinker, Rami Nassir, Lifang Hou, Garnet L Anderson, Karl T Kelsey, Emily White, Parveen Bhatti

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medical genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

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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

10 authors at 5 institutions in 1 country.

Kristina M JordahlDepartment of Epidemiology, School of Public Health, University of Washington, Box 357236, Seattle, WA, 98195, USA. kjordahl@fredhutch.org.ORCID 0000-0001-5165-5769
Amanda I PhippsDepartment of Epidemiology, School of Public Health, University of Washington, Box 357236, Seattle, WA, 98195, USA.
Timothy W RandolphDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lesley F TinkerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Rami NassirDepartment of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA.
Lifang HouDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Garnet L AndersonDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Karl T KelseyDepartments of Epidemiology and Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
Emily WhiteDepartment of Epidemiology, School of Public Health, University of Washington, Box 357236, Seattle, WA, 98195, USA.
Parveen BhattiDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Fred Hutch Cancer Center · USUniversity of Washington · USBrown University · USNorthwestern University · USUniversity of California, Davis · US

Funding

Cancer Prevention Trng-Nutrition, Exercise &GeneticsR25CA094880 · NCI · UNIVERSITY OF WASHINGTON · PI WHITE, EMILY · 2002 to 2016
$7.3M
Contributing Factors and Consequences of Cancer Health DisparitiesT32CA094880 · NCI · UNIVERSITY OF WASHINGTON · PI Christopher I Li, AMANDA IRENE PHIPPS · 2017 to 2026
$3.7M
American Cancer Society 125299-RSG-13-100-01-CCENCI NIH HHS R25 CA094880NCI NIH HHS T32 CA094880NHLBI NIH HHS HHSN268201600001CNHLBI NIH HHS HHSN268201600002CNHLBI NIH HHS HHSN268201600003CNHLBI NIH HHS HHSN268201600004CNHLBI NIH HHS HHSN268201600018C
6 · The paper itself

Abstract

backgroundThough bladder cancer has been the subject of many well-powered genome-wide association studies, the mechanisms involving bladder-cancer-associated single nucleotide polymorphisms (SNPs) remain largely unknown. This study focuses on rs798766, rs401681, rs2294008, and rs8102137, which have been associated with bladder cancer and are also cis-acting methylation quantitative loci (mQTL).

methodsAmong 412 bladder cancer cases and 424 controls from the Women's Health Initiative (WHI), we assessed whether the effects of these SNPs on bladder cancer are mediated through proximal DNA methylation changes in pre-diagnostic blood at mQTL-associated CpG sites, which we refer to as natural indirect effects (NIEs). We used a multiple-mediator mediation model for each of the four mQTL adjusted for matching variables and potential confounders, including race/ethnicity, smoking status, and pack-years of smoking.

resultsWhile not statistically significant, our results suggest that substantial proportions of the modest effects of rs401681 (OR

conclusionsThough larger studies are necessary, the methylation changes associated with rs401681 and rs2294008 at mQTL-associated CpG sites may be relevant for bladder carcinogenesis, and this study demonstrates how multi-omic data can be integrated to help understand the downstream effects of genetics variants.

Indexed as

Polymorphism, Single NucleotideAdultAgedAged, 80 and overAntigens, LyCarcinogenesisCarcinoma, Transitional CellCase-Control StudiesCigarette SmokingCpG IslandsDNA MethylationDNA, NeoplasmFemaleHumansMiddle AgedQuantitative Trait LociAntigens, LyDNA, NeoplasmReceptors, NicotinicBladder cancerBladder cancer risk SNPsDNA methylationMediation analysis

Identifiers

PMID33213418
PMCPMC7678190
OpenAlexW3102249834

What OpenQuestion holds

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LicenceCC BY
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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.