Meta‐analysis of the association between P53 codon 72 polymorphisms and gastric cancer

Zhang, Qi; Ma, Yingyu; Wang, Hui-Ju; Shao, Changming; Zhang, Jun; Ye, Zai-yuan

doi:10.1002/jso.23233

Cited by 15 publications

(15 citation statements)

References 61 publications

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“…Our data are consistent with the findings published by Katkoori et al demonstrating that the P/P genotype is a significant risk factor for colon cancer in African Americans (42). Zhang et al, likewise found that the Pro allele and P/P genotype were enriched in Asian gastric cancer patients compared to non-cancer control individuals (43). Sullivan et al reported that Pro72 cells primarily enter a G1-arrest with minimal apoptosis at chemotherapeutic doses that result in a strong apoptotic response in Arg72 cells (14).…”

Section: Discussionmentioning

confidence: 98%

Transcriptomes and shRNA Suppressors in a TP53 Allele–Specific Model of Early-Onset Colon Cancer in African Americans

Weige¹,

Birtwistle

Mallick

et al. 2014

Molecular Cancer Research

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African Americans are disproportionately affected by early-onset, high-grade malignancies. A fraction of this cancer health disparity can be explained by genetic differences between individuals of African or European descent. Here the wild-type Pro/Pro genotype at the TP53Pro72Arg (P72R) polymorphism (SNP: rs1042522) is more frequent in African Americans with cancer than in African Americans without cancer (51% vs 37%), and is associated with a significant increase in the rates of cancer diagnosis in African Americans. To test the hypothesis that p53 allele-specific gene expression may contribute to African American cancer disparities, p53 hemizygous knockout variants were generated and characterized in the RKO colon carcinoma cell line, which is wild-type for p53 and heterozygous at the TP53Pro72Arg locus. Transcriptome profiling, using RNAseq, in response to the DNA-damaging agent etoposide revealed a large number of p53-regulated transcripts, but also a subset of transcripts that were TP53Pro72Arg allele specific. In addition, a shRNA-library suppressor screen for p53 allele-specific escape from p53-induced arrest was performed. Several novel RNAi suppressors of p53 were identified, one of which, PRDM1β (BLIMP-1), was confirmed to be an Arg-specific transcript. PRDM1β silences target genes by recruiting H3K9 trimethyl (H3K9me3) repressive chromatin marks, and is necessary for stem cell differentiation. These results reveal a novel model for African American cancer disparity, in which the TP53 codon 72 allele influences lifetime cancer risk by driving damaged cells to differentiation through an epigenetic mechanism involving gene silencing. Implications TP53 P72R polymorphism significantly contributes to increased African American cancer disparity.

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Section: Discussionmentioning

confidence: 98%

Transcriptomes and shRNA Suppressors in a TP53 Allele–Specific Model of Early-Onset Colon Cancer in African Americans

Weige¹,

Birtwistle

Mallick

et al. 2014

Molecular Cancer Research

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“…Allele frequencies of rs1042522G>C differ notably among populations with values for the rs1042522C (Pro) variant ranging from ~63% in African Blacks to ~41% in Asians or ~17% in Swedish Saamis [30]. The relevance of these major ethnic and geographical variations in TP53 rs1042522 profiles are supported by two recent meta–analyses showing a significant association between the rs1042522C (Pro) variant and GC in Eastern Asian populations but not in Caucasians and South Americans [31, 32]. Similarly, some opposing associations have been reported among ethnicities when considering the location and histological subtypes of GC [33, 34].…”

Section: Discussionmentioning

confidence: 99%

“…[28] and Zhang et al . [32] observed a significantly lower frequency of the rs1042522C (Pro) allele in GC patients compared to HCs. Moreover, an Italian study by De Feo et al .…”

Section: Discussionmentioning

confidence: 99%

Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype

et al. 2017

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Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55–2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22–2.57), and family history of GC (OR: 2.87; 95% CI: 1.85–4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56–0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56–0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38–0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30–2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.

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“…However, their biological and clinical significance in most cases is unknown. A notable exception in relation to cancer susceptibility is the TP53 P72R polymorphism, the main P/P allele being preferentially found in African Americans with colon cancer [29] and Asians with gastric cancer [30]. It has been proposed that the TP53 P/P-related cancer susceptibility is due to a faster accumulation of mutations and a larger pool of putative cancer-initiating cells.…”

Section: Genetic Polymorphisms and Cancer Gene Mutationsmentioning

confidence: 99%

Racial Differences in Cancer Susceptibility and Survival: More Than the Color of the Skin?

2017

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Epidemiological studies point to race as a determining factor in cancer susceptibility. In US registries recording cancer incidence and survival by race (distinguishing “Black versus White”), individuals of African ancestry have a globally increased risk of malignancies compared to Caucasians and Asian Americans. Differences in socioeconomic status and health care access play a key role. However, the lesser disease susceptibility of Hispanic populations with comparable life-styles and socioeconomic status as African Americans, (“Hispanic paradox”) points to the concomitant importance of genetic determinants. Here, we overview the molecular basis of racial disparity in cancer susceptibility ranging from genetic polymorphisms and cancer-driver gene mutations to obesity, chronic inflammation and immune responses. We discuss implications for race-adapted cancer screening programs and clinical trials to reduce disparities in cancer burden.

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Meta‐analysis of the association between P53 codon 72 polymorphisms and gastric cancer

Abstract: In conclusion, the P53 codon 72 polymorphisms seems to be associated with gastric cancer risk and the analyses suggested that P53 codon 72 polymorphisms may be an important biomarker of gastric cancer susceptibility for Asians.

Cited by 15 publications

References 61 publications

Transcriptomes and shRNA Suppressors in a TP53 Allele–Specific Model of Early-Onset Colon Cancer in African Americans

Transcriptomes and shRNA Suppressors in a TP53 Allele–Specific Model of Early-Onset Colon Cancer in African Americans

Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype

Racial Differences in Cancer Susceptibility and Survival: More Than the Color of the Skin?

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