Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Genetic regulation of spermine oxidase activity and cancer risk: a Mendelian randomization study

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Detection of biological signals from a live mammalian muscle using an early stage diamond quantum sensor

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Infants with congenital heart defects have reduced brain volumes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Interindividual variability of electric fields during transcranial temporal interference stimulation (tTIS)

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Using machine learning for predicting intensive care unit resource use during the COVID-19 pandemic in Denmark

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Identifying dominant-negative actions of a dopamine transporter variant in patients with parkinsonism and neuropsychiatric disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Translating polygenic risk scores for clinical use by estimating the confidence bounds of risk prediction

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genetic, Clinical, and Sociodemographic Factors Associated With Stimulant Treatment Outcomes in ADHD

    Research output: Contribution to journalJournal articleResearchpeer-review

  • João Fadista
  • Victor Yakimov
  • Urmo Võsa
  • Christine S Hansen
  • Silva Kasela
  • Line Skotte
  • Frank Geller
  • Julie Courraud
  • Tõnu Esko
  • Viktorija Kukuškina
  • Alfonso Buil
  • Mads Melbye
  • Thomas M Werge
  • David M Hougaard
  • Lili Milani
  • Jonas Bybjerg-Grauholm
  • Arieh S Cohen
  • Bjarke Feenstra
View graph of relations

Spermine oxidase (SMOX) catalyzes the oxidation of spermine to spermidine. Observational studies have reported SMOX as a source of reactive oxygen species associated with cancer, implying that inhibition of SMOX could be a target for chemoprevention. Here we test causality of SMOX levels with cancer risk using a Mendelian randomization analysis. We performed a GWAS of spermidine/spermine ratio to identify genetic variants associated with regulation of SMOX activity. Replication analysis was performed in two datasets of SMOX gene expression. We then did a Mendelian randomization analysis by testing the association between the SMOX genetic instrument and neuroblastoma, gastric, lung, breast, prostate, and colorectal cancers using GWAS summary statistics. GWAS of spermidine/spermine ratio identified SMOX locus (P = 1.34 × 10-49) explaining 32% of the variance. The lead SNP rs1741315 was also associated with SMOX gene expression in newborns (P = 8.48 × 10-28) and adults (P = 2.748 × 10-8) explaining 37% and 6% of the variance, respectively. Genetically determined SMOX activity was not associated with neuroblastoma, gastric, lung, breast, prostate nor colorectal cancer (P > 0.05). A PheWAS of rs1741315 did not reveal any relevant associations. Common genetic variation in the SMOX gene was strongly associated with SMOX activity in newborns, and less strongly in adults. Genetic down-regulation of SMOX was not significantly associated with lower odds of neuroblastoma, gastric, lung, breast, prostate and colorectal cancer. These results may inform studies of SMOX inhibition as a target for chemoprevention.

Original languageEnglish
Article number17463
JournalScientific Reports
Volume11
Issue number1
Pages (from-to)17463
ISSN2045-2322
DOIs
Publication statusPublished - 31 Aug 2021

ID: 67621249