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  • Fadista, JoãoLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Danish Serum Institute, Copenhagen (författare)

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

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-08-31
  • Springer Science and Business Media LLC,2021

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:26bf45a1-7b43-4015-9831-085fd805529e
  • https://lup.lub.lu.se/record/26bf45a1-7b43-4015-9831-085fd805529eURI
  • https://doi.org/10.1038/s41598-021-97069-xDOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Yakimov, VictorDanish Serum Institute, Copenhagen (författare)
  • Võsa, UrmoUniversity of Tartu (författare)
  • Hansen, Christine S.Danish Serum Institute, Copenhagen (författare)
  • Kasela, SilvaUniversity of Tartu (författare)
  • Skotte, LineDanish Serum Institute, Copenhagen (författare)
  • Geller, FrankDanish Serum Institute, Copenhagen (författare)
  • Courraud, JulieDanish Serum Institute, Copenhagen (författare)
  • Esko, TõnuBroad Institute (författare)
  • Kukuškina, ViktorijaUniversity of Tartu (författare)
  • Buil, AlfonsoLundbeck Foundation Initiative for Integrative Psychiatric Research (författare)
  • Melbye, MadsStanford University,University of Copenhagen (författare)
  • Werge, Thomas M.Lundbeck Foundation Initiative for Integrative Psychiatric Research (författare)
  • Hougaard, David M.Danish Serum Institute, Copenhagen (författare)
  • Milani, LiliUniversity of Tartu (författare)
  • Bybjerg-Grauholm, JonasDanish Serum Institute, Copenhagen (författare)
  • Cohen, Arieh S.Danish Serum Institute, Copenhagen (författare)
  • Feenstra, BjarkeDanish Serum Institute, Copenhagen (författare)
  • Translationell muskelforskningForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Scientific Reports: Springer Science and Business Media LLC11:12045-2322

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