Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene.

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>A, rs12226937: G>A, and rs61761074: T>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>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>G substitution at nucleotide position 615 in the second intron of the KRAS gene (rs61761074) may represent a promising genetic marker of NSCLC.

Keywords

K-RAS, lung cancer, NF-Y binding, regulatory SNPs (rSNP)

Citation

Antontseva Elena V, Matveeva Marina Yu, Bondar Natalia P, Kashina Elena V, Leberfarb Elena Yu, Bryzgalov Leonid O, Gervas Polina A, Ponomareva Anastasia A, Cherdyntseva Nadezhda V, Orlov Yury L, Merkulova Tatiana I. Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene. 873-883.