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

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 5; pp. 2307 - 2310
• Main Authors: YA JUN HU, KOROTKOV, Konstantin V, DOLAN, M. Eileen, GLADYSHEV, Vadim N, DIAMOND, Alan M, MEHTA, Rajeshwari, HATFIELD, Dolph L, ROTIMI, Charles N, LUKE, Amy, PREWITT, T. Elaine, COOPER, Richard S, STOCK, Wendy, VOKES, Everett E
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.2001
• Subjects: 3' Untranslated Regions - genetics; Adult; African Continental Ancestry Group - genetics; Biological and medical sciences; DNA - blood; DNA - genetics; DNA, Neoplasm - genetics; European Continental Ancestry Group - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Humans; Loss of Heterozygosity; Male; Medical sciences; Neoplasms - genetics; Polymorphism, Single Nucleotide - physiology; Proteins - genetics; Selenoproteins; Sep15 gene; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; American; Tumoral tissue; Non coding sequence; Carcinogenesis; Epidemiology; Insertion mutation; Intestinal disease; Genetics; Colon; Selenium; Human; Nucleotide sequence; 3' terminal-Sequence; Genotype; Malignant tumor; In vitro; African; Colonic disease; Allele; DNA; Risk factor; Loss of heterozygosity; Digestive diseases; Mutation; Lymphocyte; Polymorphism
• ISSN: 0008-5472

Selenium has been shown to prevent cancer in a variety of animal model systems. Both epidemiological studies and supplementation trials have supported its efficacy in humans. However, the mechanism by which selenium suppresses tumor development remains unknown. Selenium is present in known human selenoproteins as the amino acid selenocysteine (Sec). Sec is inserted cotranslationally in response to UGA codons within selenoprotein mRNAs in a process requiring a sequence within the 3'-untranslated region (UTR), referred to as a Sec insertion sequence (SECIS) element. Recently, a human Mr 15,000 selenoprotein (Sep15) was identified that contains an in-frame UGA codon and a SECIS element in the 3'-UTR. Examination of the available cDNA sequences 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 function in a selenium-dependent manner. This, together with genetic data indicating loss of heterozygosity at the Sep15 locus in certain human tumor types, suggests that Sep15 may be involved in cancer development, risk, or both.