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Sökning: WFRF:(Grauholm Jonas) > Genetic regulation ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004544naa a2200505 4500
001oai:lup.lub.lu.se:26bf45a1-7b43-4015-9831-085fd805529e
003SwePub
008210917s2021 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/26bf45a1-7b43-4015-9831-085fd805529e2 URI
0247 a https://doi.org/10.1038/s41598-021-97069-x2 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Fadista, Joãou Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,University of Helsinki,Danish Serum Institute, Copenhagen4 aut0 (Swepub:lu)med-jft
2451 0a Genetic regulation of spermine oxidase activity and cancer risk : a Mendelian randomization study
264 c 2021-08-31
264 1b Springer Science and Business Media LLC,c 2021
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
7001 a Yakimov, Victoru Danish Serum Institute, Copenhagen4 aut
7001 a Võsa, Urmou University of Tartu4 aut
7001 a Hansen, Christine S.u Danish Serum Institute, Copenhagen4 aut
7001 a Kasela, Silvau University of Tartu4 aut
7001 a Skotte, Lineu Danish Serum Institute, Copenhagen4 aut
7001 a Geller, Franku Danish Serum Institute, Copenhagen4 aut
7001 a Courraud, Julieu Danish Serum Institute, Copenhagen4 aut
7001 a Esko, Tõnuu Broad Institute4 aut
7001 a Kukuškina, Viktorijau University of Tartu4 aut
7001 a Buil, Alfonsou Lundbeck Foundation Initiative for Integrative Psychiatric Research4 aut
7001 a Melbye, Madsu Stanford University,University of Copenhagen4 aut
7001 a Werge, Thomas M.u Lundbeck Foundation Initiative for Integrative Psychiatric Research4 aut
7001 a Hougaard, David M.u Danish Serum Institute, Copenhagen4 aut
7001 a Milani, Liliu University of Tartu4 aut
7001 a Bybjerg-Grauholm, Jonasu Danish Serum Institute, Copenhagen4 aut
7001 a Cohen, Arieh S.u Danish Serum Institute, Copenhagen4 aut
7001 a Feenstra, Bjarkeu Danish Serum Institute, Copenhagen4 aut
7102 a Translationell muskelforskningb Forskargrupper vid Lunds universitet4 org
7730 t Scientific Reportsd : Springer Science and Business Media LLCg 11:1q 11:1x 2045-2322
8564 u http://dx.doi.org/10.1038/s41598-021-97069-xx freey FULLTEXT
8564 u https://www.nature.com/articles/s41598-021-97069-x.pdf
8564 8u https://lup.lub.lu.se/record/26bf45a1-7b43-4015-9831-085fd805529e
8564 8u https://doi.org/10.1038/s41598-021-97069-x

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