Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a retrospective study of 399 patients with ulcerative colitis, 27 patients had colitic arthritis, 17 had ankylosing spondylitis, and 20 had clubbing of the fingers. Colitic arthritis and ankylosing spondylitis were not related to severity, extent of involvement, or duration of colitis. A significant association between colitic arthropathy and other complications of ulcerative colitis, such as pseudopolyposis, perianal disease, eye lesions, skin eruptions, aphthous ulceration, and liver disease has been demonstrated. The outcome of the first referred attack of colitis in the presence of colitic arthritis and ankylosing spondylitis remained uninfluenced. Clubbing of fingers was related to severity, extent of involvement, and length of the history of colitis. A significant association between clubbing of the fingers and carcinoma of the colon, pseudopolyposis, toxic dilatation, and arthropathy has been shown. The frequency of surgical intervention in patients with clubbing was higher but the overall mortality was not significantly different from the patients without clubbing.
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PMID:Arthropathy, ankylosing spondylitis, and clubbing of fingers in ulcerative colitis. 547 6

HPGDand SLCO2A1 genes encode components of the prostaglandin catabolic pathway, with HPGD encoding the degradative enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and SLCO2A1 encoding the prostaglandin transporter PGT that brings substrate to 15-PGDH. HPGD-null mice show increased prostaglandin E2 (PGE2), marked susceptibility to developing colon tumors, and resistance to colon tumor prevention by nonsteroidal anti-inflammatory drugs (NSAID). But in humans, HPGD and SLCO2A1 mutations have only been associated with familial digital clubbing. We, here, characterize a family with digital clubbing and early-onset colon neoplasia. Whole-exome sequencing identified a heterozygous nonsense mutation (G104X) in the SLCO2A1 gene segregating in 3 males with digital clubbing. Two of these males further demonstrated notably early-onset colon neoplasia, 1 with an early-onset colon cancer and another with an early-onset sessile serrated colon adenoma. Two females also carried the mutation, and both these women developed sessile serrated colon adenomas without any digital clubbing. Males with clubbing also showed marked elevations in the levels of urinary prostaglandin E2 metabolite, PGE-M, whereas, female mutation carriers were in the normal range. Furthermore, in the male proband, urinary PGE-M remained markedly elevated during NSAID treatment with either celecoxib or sulindac. Thus, in this human kindred, a null SLCO2A1 allele mimics the phenotype of the related HPGD-null mouse, with increased prostaglandin levels that cannot be normalized by NSAID therapy, plus with increased colon neoplasia. The development of early-onset colon neoplasia in male and female human SLCO2A1 mutation carriers suggests that disordered prostaglandin catabolism can mediate inherited susceptibility to colon neoplasia in man.
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PMID:Inactivating mutation in the prostaglandin transporter gene, SLCO2A1, associated with familial digital clubbing, colon neoplasia, and NSAID resistance. 2483 73