Sökning: WFRF:(Grauholm Jonas) > Genetic regulation ...
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000 | 04544naa a2200505 4500 | |
001 | oai:lup.lub.lu.se:26bf45a1-7b43-4015-9831-085fd805529e | |
003 | SwePub | |
008 | 210917s2021 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/26bf45a1-7b43-4015-9831-085fd805529e2 URI |
024 | 7 | a https://doi.org/10.1038/s41598-021-97069-x2 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | 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 |
245 | 1 0 | a Genetic regulation of spermine oxidase activity and cancer risk : a Mendelian randomization study |
264 | c 2021-08-31 | |
264 | 1 | b 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 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
700 | 1 | a Yakimov, Victoru Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Võsa, Urmou University of Tartu4 aut |
700 | 1 | a Hansen, Christine S.u Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Kasela, Silvau University of Tartu4 aut |
700 | 1 | a Skotte, Lineu Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Geller, Franku Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Courraud, Julieu Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Esko, Tõnuu Broad Institute4 aut |
700 | 1 | a Kukuškina, Viktorijau University of Tartu4 aut |
700 | 1 | a Buil, Alfonsou Lundbeck Foundation Initiative for Integrative Psychiatric Research4 aut |
700 | 1 | a Melbye, Madsu Stanford University,University of Copenhagen4 aut |
700 | 1 | a Werge, Thomas M.u Lundbeck Foundation Initiative for Integrative Psychiatric Research4 aut |
700 | 1 | a Hougaard, David M.u Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Milani, Liliu University of Tartu4 aut |
700 | 1 | a Bybjerg-Grauholm, Jonasu Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Cohen, Arieh S.u Danish Serum Institute, Copenhagen4 aut |
700 | 1 | a Feenstra, Bjarkeu Danish Serum Institute, Copenhagen4 aut |
710 | 2 | a Translationell muskelforskningb Forskargrupper vid Lunds universitet4 org |
773 | 0 | t Scientific Reportsd : Springer Science and Business Media LLCg 11:1q 11:1x 2045-2322 |
856 | 4 | u http://dx.doi.org/10.1038/s41598-021-97069-xx freey FULLTEXT |
856 | 4 | u https://www.nature.com/articles/s41598-021-97069-x.pdf |
856 | 4 8 | u https://lup.lub.lu.se/record/26bf45a1-7b43-4015-9831-085fd805529e |
856 | 4 8 | u https://doi.org/10.1038/s41598-021-97069-x |
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