Association between TP53 R249S mutation and polymorphisms in TP53 intron 1 in hepatocellular carcinoma

作者：Ortiz Cuaran Sandra; Cox David; Villar Stephanie; Friesen Marlin D; Durand Geoffroy; Chabrier Amelie; Khuhaprema Thiravud; Sangrajrang Sulee****; Ognjanovic Simona; Groopman John D; Hainaut Pierre^*; Le Calvez Kelm Florence

来源：Genes, Chromosomes and Cancer, 2013, 52(10): 912-919.

DOI：10.1002/gcc.22086

Over 100 single nucleotide polymorphisms (SNP) are validated in the TP53 tumor suppressor gene. They define haplotypes, which may differ in their activities. Therefore, mutation in cancer may occur at different rates depending upon haplotypes. However, these associations may be masked by differences in mutations types and causes of mutagenesis. We have analyzed the associations between 19 SNPs spanning the TP53 locus and a single specific aflatoxin-induced TP53 mutation (R249S) in 85 in hepatocellular carcinoma cases and 132 controls from Thailand. An association with R249S mutation (P=0.007) was observed for a combination of two SNPs (rs17882227 and rs8064946) in a linkage disequilibrium block extending from upstream of exon 1 to the first half of intron 1. This domain contains two coding sequences overlapping with TP53 (WRAP53 and Hp53int1) suggesting that sequences in TP53 intron 1 encode transcripts that may modulate R249S mutation rate in HCC.

• 出版日期2013-10