title: Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene.
abstract: There are two regulatory single nucleotide polymorphisms (rSNPs) at the beginning of the second intron of the mouse K-ras gene that are strongly associated with lung cancer susceptibility. We performed functional analysis of three SNPs (rs12228277: T greater than A, rs12226937: G greater than A, and rs61761074: T greater than G) located in the same region of human KRAS. We found that rs12228277 and rs61761074 result in differential binding patterns of lung nuclear proteins to oligonucleotide probes corresponding two alternative alleles; in both cases, the transcription factor NF-Y is involved. G greater than A substitution (rs12226937) had no effect on the binding of lung nuclear proteins. However, all the nucleotide substitutions under study showed functional effects in a luciferase reporter assay. Among them, rs61761074 demonstrated a significant correlation with allele frequency in non-small-cell lung cancer (NSCLC). Taken together, the results of our study suggest that a T greater than G substitution at nucleotide position 615 in the second intron of the KRAS gene (rs61761074) may represent a promising genetic marker of NSCLC.
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Lavrentieva avenue 10, Novosibirsk 630090, Russian Federation.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Antontseva
authors.forename: Marina Yu
authors.initials: MY
authors.lastname: Matveeva
authors.forename: Natalia P
authors.initials: NP
authors.lastname: Bondar
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kashina
authors.forename: Elena Yu
authors.initials: EY
authors.lastname: Leberfarb
authors.forename: Leonid O
authors.initials: LO
authors.lastname: Bryzgalov
authors.forename: Polina A
authors.initials: PA
authors.lastname: Gervas
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Ponomareva
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Cherdyntseva
authors.forename: Yury L
authors.initials: YL
authors.lastname: Orlov
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Merkulova
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D016022:Case-Control Studies; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005787:Gene Frequency; D011905:Genes, ras; D005819:Genetic Markers; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics*; D018307:Neoplasms, Squamous Cell / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012800:Siberia; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; D050993:GATA6 Transcription Factor; D005819:Genetic Markers; D018631:ras Proteins