{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:20:09Z","timestamp":1789737609331,"version":"4.0.1"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,6,24]]},"abstract":"<jats:p>\n                    Most sporadic colon adenomas acquire mutations in the adenomatous polyposis  coli gene (\n                    <jats:italic>APC<\/jats:italic>\n                    ) and show defects in\n                    <jats:italic>APC<\/jats:italic>\n                    -dependent signaling.\n                    <jats:italic>APC<\/jats:italic>\n                    influences the expression of several genes, including the  c-\n                    <jats:italic>myc<\/jats:italic>\n                    oncogene and its antagonist\n                    <jats:italic>Mad1<\/jats:italic>\n                    . Ornithine  decarboxylase (ODC), the first enzyme in polyamine synthesis, is a  transcriptional target of c-\n                    <jats:italic>myc<\/jats:italic>\n                    and a modifier of\n                    <jats:italic>APC<\/jats:italic>\n                    -dependent tumorigenesis. A single-nucleotide polymorphism exists  in intron 1 of the human\n                    <jats:italic>ODC<\/jats:italic>\n                    gene, which lies between two\n                    <jats:italic>myc<\/jats:italic>\n                    -binding domains. This region is known to affect\n                    <jats:italic>ODC<\/jats:italic>\n                    transcription, but no data exist on the relationship of this polymorphism to  risk of colorectal neoplasia in humans. We show that individuals homozygous  for the minor\n                    <jats:italic>ODC<\/jats:italic>\n                    A-allele who reported using aspirin are \u22480.10  times as likely to have an adenoma recurrence as non-aspirin users homozygous  for the major G-allele.\n                    <jats:italic>Mad1<\/jats:italic>\n                    selectively suppressed the activity of  the\n                    <jats:italic>ODC<\/jats:italic>\n                    promoter containing the A-allele, but not the G-allele, in a  human colon cancer-derived cell line (HT29). Aspirin (\u226510 \u03bcM) did not  affect\n                    <jats:italic>ODC<\/jats:italic>\n                    allele-specific promoter activity but did activate  polyamine catabolism and lower polyamine content in HT29 cells. We propose  that the\n                    <jats:italic>ODC<\/jats:italic>\n                    polymorphism and aspirin act independently to reduce the  risk of adenoma recurrence by suppressing synthesis and activating catabolism,  respectively, of colonic mucosal polyamines. These findings confirm the  hypothesis that the\n                    <jats:italic>ODC<\/jats:italic>\n                    polymorphism is a genetic marker for colon  cancer risk, and support the use of ODC inhibitors and aspirin, or other  nonsteroidal antiinflammatory drugs (NSAIDs), in combination as a strategy for  colon cancer prevention.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1332465100","type":"journal-article","created":{"date-parts":[[2003,6,24]],"date-time":"2003-06-24T13:47:39Z","timestamp":1056462459000},"page":"7859-7864","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":160,"title":["Pronounced reduction in adenoma recurrence associated with aspirin use  and a polymorphism in the ornithine decarboxylase gene"],"prefix":"10.1073","volume":"100","author":[{"given":"Mar\u00eda Elena","family":"Mart\u00ednez","sequence":"first","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly E.","family":"Fultz","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen","family":"Babbar","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Yerushalmi","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Qu","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Guo","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Boorman","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Einspahr","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; and  Lankenau Institute for Medical Research,  Wynnewood, PA 19096"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Alberts","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center,  Mel and Enid Zuckerman College of Public  Health, Graduate Program in Biochemistry and  Molecular and Cellular Biology, Cancer Biology  Interdisciplinary Program, and Department of  Medicine, University of Arizona, Tucson, AZ 85724; 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