Characterization of Novel and Uncharacterized p53 SNPs in the Chinese Population – Intron 2 SNP Co-Segregates with the Common Codon 72 Polymorphism

Abstract

Multiple single nucleotide polymorphisms (SNPs) have been identified in the tumor suppressor gene p53, though the relevance of many of them is unclear. Some of them are also differentially distributed in various ethnic populations, suggesting selective functionality. We have therefore sequenced all exons and flanking regions of p53 from the Singaporean Chinese population and report here the characterization of some novel and uncharacterized SNPs - four in intron 1 (nucleotide positions 8759/10361/10506/11130), three in intron 3 (11968/11969/11974) and two in the 3′UTR (19168/19514). Allelic frequencies were determined for all these and some known SNPs, and were compared in a limited scale to leukemia and lung cancer patient samples. Intron 2 (11827) and 7 (14181/14201) SNPs were found to have a high minor allele frequency of between 26–47%, in contrast to the lower frequencies found in the US population, but similar in trend to the codon 72 polymorphism (SNP12139) that shows a distribution pattern correlative with latitude. Several of the SNPs were linked, such as those in introns 1, 3 and 7. Most interestingly, we noticed the co-segregation of the intron 2 and the codon 72 SNPs, the latter which has been shown to be expressed in an allele-specific manner, suggesting possible regulatory cross-talk. Association analysis indicated that the T/G alleles in both the co-segregating intron 7 SNPs and a 4tagSNP haplotype was strongly associated increased susceptibility to lung cancer in non-smoker females [OR: 1.97 (1.32, 3.394)]. These data together demonstrate high SNP diversity in p53 gene between different populations, highlighting ethnicity-based differences, and their association with cancer risk.

Biosafety evaluation of culture-expanded human chondrocytes with growth factor cocktail: a preclinical study

“…Three samples (50% of subjects) exhibited single nucleotide polymorphisms (SNPs) in the intron 7- the area between the exon 7 and exon 8. The polymorphisms were at two positions: 18442 where C was substituted with T, and 18462 where T was substituted with G. These SNPs have been previously reported as minor alleles related to ethnicity-based variations 58 .…”

Recommendations for Analyzing and ReportingTP53Gene Variants in the High-Throughput Sequencing Era

“…In the human population, hundreds of dbSNP entries describe variants in the TP53 gene or in its vicinity and several haplotype blocks have also been identified [Mechanic et al, 2007;Phang et al, 2011;Ortiz-Cuaran et al, 2013]. A large number of studies have focused on the association between common TP53 germ line variants and cancer risk (reviewed in [Whibley et al, 2009]).…”

p53: Point Mutations, SNPs and Cancer

“…Importantly, additionnal SNPs that appear specific to Chinese populations were recently reported, but their impact on cancer risk remains to be evaluated in large cohorts (Phang et al, 2011). SNPs that could influence cancer risk need to be precisely evaluated in other p53 family members as well.…”