Distribution and functional consequences of nucleotide polymorphisms in the 3 '-untranslated region of the human Sep15 gene

Selenium has been shown to prevent cancer in a variety of animal model syst ems. Both epidemiological studies and supplementation trials have supported its efficacy in humans. However, the mechanism by which selenium suppresse s tumor development remains unknown. Selenium is present in known human sel enoproteins as the amino acid selenocysteine (Sec), Sec is inserted cotrans lationally in response to UGA codons within selenoprotein mRNAs in a proces s requiring a sequence within the 3'-untranslated region (UTR), referred to as a Sec insertion sequence (SECIS) element. Recently, a human M-r 15,000 selenoprotein (Sep15) was identified that contains an in-frame UGA codon an d a SECIS element in the 3'-UTR, Examination of the available cDNA sequence s for this protein revealed two polymorphisms located at position 811 (C/T) and at position 1125 (G/A) located within the 3'-UTR, Here, we demonstrate significant differences in Sep15 allele frequencies by ethnicity and that the identity of the nucleotides at the polymorphic sites influences SECIS f unction in a selenium-dependent manner. This, together with genetic data in dicating loss of heterozygosity at the Sep15 locus in certain human tumor t ypes. suggests that Sep15 may be involved in cancer development. risk, or b oth.