Evidence map›Paper›PMID 31246991›Full record

ArticlePloS one2019

Post genome-wide gene-environment interaction study: The effect of genetically driven insulin resistance on breast cancer risk using Mendelian randomization.

Su Yon Jung, Nicholas Mancuso, Jeanette Papp, Eric Sobel, Zuo-Feng Zhang

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

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 3 pooled it
1.3field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 3 syntheses or guidelines pooled it, 12 citations in OpenAlex.

  1. Linking Physical Activity to Breast Cancer Risk via the Insulin/Insulin-like Growth Factor Signaling System, Part 2: The Effect of Insulin/Insulin-like Growth Factor Signaling on Breast Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022
    Pooled it
  2. Pooled it
  3. Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020
    Pooled it
  4. Effect of Metformin on Breast Density in Overweight/Obese Premenopausal Women.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021
    Trial
  5. Article
  6. Article
  7. Insulin Resistance and Cancer: In Search for a Causal Link.International journal of molecular sciences · 2021
    Review
  8. Article
  9. Article
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

5 authors at 1 institution in 1 country.

Su Yon JungTranslational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, Los Angeles, CA, United States of America.ORCID 0000-0002-0513-1830
Nicholas MancusoDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States of America.
Jeanette PappDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States of America.
Eric SobelDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States of America.
Zuo-Feng ZhangDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States of America.
University of California, Los Angeles · US

Funding

Insulin-Resistance Genetic and Epigenetic Variants and Their Interactions with Lifestyle Factors in Postmenopausal Breast CancerK01NR017852 · NINR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JUNG, SU YON · 2019 to 2021
$289k
NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100046CNIA NIH HHS HHSN271201100004CNINR NIH HHS K01 NR017852WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004C
6 · The paper itself

Abstract

purposeThe role of insulin resistance (IR) in developing postmenopausal breast cancer has not been thoroughly resolved and may be confounded by lifestyle factors such as obesity. We examined whether genetically determined IR is causally associated with breast cancer risk.

methodsWe conducted Mendelian randomization (MR) analyses using individual-level data from our previous meta-analysis of a genome-wide association study (GWAS) (n = 11,109 non-Hispanic white postmenopausal women). Four single-nucleotide polymorphisms were associated with fasting glucose (FG), 2 with fasting insulin (FI), and 6 with homeostatic model assessment-IR (HOMA-IR) but were not associated with obesity. We used this GWAS to employ hazard ratios (HRs) for breast cancer risk by adjusting for potential confounding factors.

resultsNo direct association was observed between comprising 12 IR genetic instruments and breast cancer risk (HR = 0.93, 95% CI: 0.76-1.14). In phenotype-specific analysis, genetically elevated FG was associated with reduced risk for breast cancer (main contributor of this MR-effect estimate: G6PC2 rs13431652; HR = 0.59, 95% CI: 0.35-0.99). Genetically driven FI and HOMA-IR were not significantly associated. Stratification analyses by body mass index, exercise, and dietary fat intake with combined phenotypes showed that genetically elevated IR was associated with greater breast cancer risk in overall obesity and inactive subgroups (single contributor: MTRR/LOC729506 rs13188458; HR = 2.21, 95% CI: 1.03-4.75).

conclusionsWe found complex evidence for causal association between IR and risk of breast cancer, which may support the potential value of intervention trials to lower IR and reduce breast cancer risk.

Indexed as

Gene-Environment InteractionBreast NeoplasmsFemaleGenome-Wide Association StudyHumansInsulin ResistanceMendelian Randomization AnalysisObesityPolymorphism, Single NucleotidePostmenopauseRisk Factors

Identifiers

PMID31246991
PMCPMC6597082
OpenAlexW2954635194

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.