Evidence map›Paper›PMID 32424261›Full record

ArticleProstate cancer and prostatic diseases2021

Association between metformin medication, genetic variation and prostate cancer risk.

Min Joon Lee, Viranda H Jayalath, Wei Xu, Lin Lu, Stephen J Freedland, Neil E Fleshner, Girish S Kulkarni, Antonio Finelli, Theodorus H van der Kwast, Robert J Hamilton

Abstract read
PubMed Publisher
In one paragraph

Article in Prostate cancer and prostatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
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  4. Review
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  7. Targeting of the tumor immune microenvironment by metformin.Journal of cell communication and signaling · 2022
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Metformin and Malignant Tumors: Not Over the Hill.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Min Joon LeeDivision of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-2722-8526
Viranda H JayalathDivision of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Wei XuDepartment of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Lin LuDepartment of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Stephen J FreedlandDivision of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Neil E FleshnerDivision of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Girish S KulkarniDivision of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Antonio FinelliDivision of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Theodorus H van der KwastDepartment of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-8640-5786
Robert J HamiltonDivision of Urology, Department of Surgery, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada. rob.hamilton@uhn.ca.
University Health Network · CACedars-Sinai Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe relationship between metformin use and prostate cancer risk remains controversial. Genetic variation in metformin metabolism pathways appears to modify metformin glycemic control and the protective association with some cancers. However, no studies to date have examined this pharmacogenetic interaction and prostate cancer chemoprevention.

methodsClinical data and germline DNA were collected from our prostate biopsy database between 1996 and 2014. In addition to a genome-wide association study (GWAS), 27 single nucleotide polymorphisms (SNPs) implicated in metformin metabolism were included on a custom SNP array. Associations between metformin use and risk of high-grade (Grade Group ≥ 2) and overall prostate cancer were explored using a case-control design. Interaction between the candidate/GWAS SNPs and the metformin-cancer association was explored using a case-only design.

resultsAmong 3481 men, 132 (4%) were taking metformin at diagnosis. Metformin users were older, more likely non-Caucasian, and had higher body mass index, Gleason score, and number of positive cores. Overall, 2061 (59%) were diagnosed with prostate cancer, of which 922 (45%) were high-grade. After adjusting for baseline characteristics, metformin use was associated with higher risk of high-grade prostate cancer (OR = 1.76, 95% CI 1.1-2.9, p = 0.02) and overall prostate cancer (OR = 1.77, 95% CI 1.1-2.9, p = 0.03). None of the 27 candidate SNPs in metformin metabolic pathways had significant interaction with the metformin-cancer association. Among the GWAS SNPs, one SNP (rs149137006) had genome-wide significant interaction with metformin for high-grade prostate cancer, and another, rs115071742, for overall prostate cancer. They were intronic and intergenic SNPs, respectively, with largely uncharacterized roles in prostate cancer chemoprevention.

conclusionsIn our cohort, metformin use was associated with increased risk of being diagnosed with prostate cancer. While SNPs involved in metformin metabolism did not have modifying effects on the association with disease risk, one intronic and one intergenic SNP from the GWAS study did, and these require further study.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single NucleotideAgedBiopsyCase-Control StudiesDNA, NeoplasmGenome-Wide Association StudyHumansHypoglycemic AgentsMaleMetforminMiddle AgedNeoplasm GradingProstatic NeoplasmsRetrospective StudiesRisk FactorsDNA, NeoplasmHypoglycemic AgentsMetformin

Identifiers

PMID32424261
OpenAlexW3024250410

What OpenQuestion holds

Textmetadata
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.