Evidence map›Paper›PMID 27102200›Full record

Trial reportBMC cancer2016

Alcohol-related breast cancer in postmenopausal women - effect of CYP19A1, PPARG and PPARGC1A polymorphisms on female sex-hormone levels and interaction with alcohol consumption and NSAID usage in a nested case-control study and a randomised controlled trial.

Tine Iskov Kopp, Ditte Marie Jensen, Gitte Ravn-Haren, Arieh Cohen, Helle Molgaard Sommer, Lars Ove Dragsted, Anne Tjonneland, David Michael Hougaard, Ulla Vogel

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02463383 (Alcohol-related Breast Cancer in Postmenopausal Women - Effect of PPARG2pro12ala Polymorphism on Female Sex-hormone Levels and Interaction With Alcohol Consumption and NSAID Usage), which is not on this map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.4field-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.

NCT02463383 early_phase1completednot on this map

Alcohol-related Breast Cancer in Postmenopausal Women - Effect of PPARG2pro12ala Polymorphism on Female Sex-hormone Levels and Interaction With Alcohol Consumption and NSAID Usage

TypeinterventionalSponsorProfessor Lars Ove DragstedRan2013 to 2015Enrolled25ConditionsBreast CancerArmsIbuprofen Tab 400 MG, Placebo tab
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Alcohol's Effects on Breast Cancer in Women.Alcohol research : current reviews · 2020
    Review
  7. Article
  8. Article
  9. Review
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

9 authors at 6 institutions in 1 country.

Tine Iskov KoppTechnical University of Denmark, National Food Institute, Søborg, Denmark. tine.iskov.kopp@regionh.dk.
Ditte Marie JensenDanish Cancer Society Research Center, Copenhagen, Denmark.
Gitte Ravn-HarenTechnical University of Denmark, National Food Institute, Søborg, Denmark.
Arieh CohenDepartment of Clinical Biochemistry and Immunology, Statens Serum Institute, Copenhagen, Denmark.
Helle Molgaard SommerTechnical University of Denmark, National Food Institute, Søborg, Denmark.
Lars Ove DragstedDepartment of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Anne TjonnelandDanish Cancer Society Research Center, Copenhagen, Denmark.
David Michael HougaardDepartment of Clinical Biochemistry and Immunology, Statens Serum Institute, Copenhagen, Denmark.
Ulla VogelNational Research Centre for the Working Environment, Copenhagen, Denmark.
Statens Serum Institut · DKTechnical University of Denmark · DKUniversity of Copenhagen · DKDanish Cancer Society · DKGlostrup Hospital · DKNational Research Centre for the Working Environment · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlcohol consumption is associated with increased risk of breast cancer (BC), and the underlying mechanism is thought to be sex-hormone driven. In vitro and observational studies suggest a mechanism involving peroxisome proliferator-activated receptor gamma (PPARγ) in a complex with peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and interaction with aromatase (encoded by CYP19A1). Use of non-steroidal anti-inflammatory drugs (NSAID) may also affect circulating sex-hormone levels by modifying PPARγ activity.

methodsIn the present study we assessed whether genetic variation in CYP19A1 is associated with risk of BC in a case-control study group nested within the Danish "Diet, Cancer and Health" cohort (ncases = 687 and ncontrols = 687) and searched for gene-gene interaction between CYP19A1 and PPARGC1A, and CYP19A1 and PPARG, and gene-alcohol and gene-NSAID interactions. Association between the CYP19A1 polymorphisms and hormone levels was also examined among 339 non-HRT users. Incidence rate ratios were calculated based on Cox' proportional hazards model. Furthermore, we performed a pilot randomised controlled trial to determine the effect of the PPARG Pro(12)Ala polymorphism and the PPARγ stimulator Ibuprofen on sex-hormone levels following alcohol intake in postmenopausal women (n = 25) using linear regression.

resultsGenetic variations in CYP19A1 were associated with hormone levels (estrone: P rs11070844 = 0.009, estrone sulphate: P rs11070844 = 0.01, P rs749292 = 0.004, P rs1062033 = 0.007 and P rs10519297 = 0.03, and sex hormone-binding globulin (SHBG): P rs3751591 = 0.03) and interacted with alcohol intake in relation to hormone levels (estrone sulphate: P interaction/rs2008691 = 0.02 and P interaction/rs1062033= 0.03, and SHBG: P interaction/rs11070844 = 0.03). CYP19A1/rs3751591 was both associated with SHBG levels (P = 0.03) and with risk of BC (Incidence Rate Ratio = 2.12; 95 % Confidence Interval: 1.02-4.43) such that homozygous variant allele carriers had increased levels of serum SHBG and were at increased risk of BC. Acute intake of alcohol decreased blood estrone (P = <0.0001), estrone sulphate (P = <0.0001), and SHBG (P = 0.009) levels, whereas Ibuprofen intake and PPARG Pro(12)Ala genotype had no effect on hormone levels.

conclusionsOur results suggest that genetically determined variation in CYP19A1 is associated with differences in sex hormone levels. However, the genetically determined differences in sex hormone levels were not convincingly associated with BC risk. The results therefore indicate that the genetically determined variation in CYP19A1 contributes little to BC risk and to alcohol-mediated BC risk.

trial registrationNCT02463383, June 3, 2015.

Indexed as

AdultAlcohol DrinkingAlcoholsAnti-Inflammatory Agents, Non-SteroidalAromataseBreast NeoplasmsFemaleGenetic Association StudiesGenotypeGonadal Steroid HormonesHumansIbuprofenMiddle AgedPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPolymorphism, Single NucleotidePostmenopauseAlcoholsAnti-Inflammatory Agents, Non-SteroidalAromataseCYP19A1 protein, humanGonadal Steroid HormonesIbuprofenPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPAR gammaAlcohol consumptionBreast cancerCYP19A1EpidemiologyFemale sex-hormonesNSAIDPolymorphismsPPARGProspective nested case-control studyRandomised controlled trial

Identifiers

PMID27102200
PMCPMC4839098
OpenAlexW2338264277

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.