Genetic polymorphisms in TP53, nonsteroidal anti-inflammatory drugs and the risk of colorectal cancer: evidence for gene–environment interaction?

Tan, Xiang; Nieters, Alexandra; Hoffmeister, Michael; Beckmann, Lars; Brenner, Hermann; Chang‐Claude, Jenny

doi:10.1097/fpc.0b013e3280d5121c

Cited by 39 publications

(32 citation statements)

References 40 publications

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“…A few studies mentioned earlier also investigated haplotypes based on the TP53 polymorphisms, mainly including rs17878362:A 1 4A 2 and rs1042522:G4C [Perfumo et al, 2006;Tan et al, 2007], but also MspI RFLPs in intron 6 [Sjalander et al, 1995]. The earlier data have been inconsistent; however, Tan et al [2007], in agreement with our results, reported a significantly differential distribution of the haplotypes based on the rs17878362:A 1 4A 2 and rs1042522:G4C polymorphisms between CRC cases and controls.…”

Section: Discussionsupporting

confidence: 92%

“…Other recent studies on TP53 rs1042522:G4C, on relatively small populations, have reported an association of the C allele with increased CRC risk [Goodman et al, 2006;Pérez et al, 2006;Zhu et al, 2007;Dakouras et al, 2008;Mammano et al, 2008]. Two larger and well-designed studies [Koushik et al, 2006;Tan et al, 2007] have reported discordant results. The first study did not find any association between the TP53 rs1042522:G4C polymorphism and CRC risk, but a moderate association with risk of adenoma due to the C allele.…”

Section: Discussionmentioning

confidence: 88%

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Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic

et al. 2009

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The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk. We observed differential distribution of major haplotypes arising from four polymorphisms in the TP53 gene between cases and controls (global P<0.0001). The two most common haplotypes, A(1)GCG and A(2)CCG, were present in 81% of the cases compared to 71% of the controls. In comparison to the most common haplotype (A(1)GCG), the haplotype A(2)CCG was associated with an increased risk (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.07-1.82), while the four other haplotypes A(1)CCG (OR, 0.60; 95% CI, 0.45-0.79), A(2)GCG (OR, 0.53; 95% CI, 0.35-0.81), A(1)GTG (OR, 0.31; 95% CI, 0.15-0.64), and A(1)GCA (OR, 0.19; 95% CI, 0.07-0.51) were associated with a decreased risk. The effect of haplotypes in the TP53 gene was similar in colon (global P<0.0001) and rectal cancers (P=0.006). No association with the disease was observed with haplotypes of the CDKN1A and CDKN2A polymorphisms. The results from this study suggest that prevalent haplotypes within the TP53 gene may modulate CRC risks in the population.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 88%

Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic

et al. 2009

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“…For breast cancer, for example, results vary from protective [9][10][11][12] to no association [13][14][15] or increase in risk. [16][17][18] Similar conflicting results are also observed for esophageal, [19][20][21][22] lung, [23][24][25] and colorectal cancer [26][27][28] and other cancer types. To better understand the role of Arg72-Pro, recent meta-analysis studies have been performed for different cancer types, such as lung, 29 gastric, 30 and cervical cancer.…”

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confidence: 79%

Arg72Pro TP53 polymorphism and cancer susceptibility: A comprehensive meta‐analysis of 302 case‐control studies

Francisco

Menezes

Eluf-Neto

et al. 2010

Intl Journal of Cancer

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Arg72Pro is a common polymorphism in TP53, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of Arg72Pro in cancer, although the results are conflicting and heterogeneous. Here, we analyzed pooled data from case-control studies to determine the role of Arg72Pro in different cancer sites. We performed a systematic review and meta-analysis of 302 case-control studies that analyzed Arg72Pro in cancer susceptibility. Odds ratios were estimated for different tumor sites using distinct genetic models, and the heterogeneity between studies was explored using I 2 values and meta-regression. We adopted quality criteria to classify the studies. Subgroup analyses were done for tumor sites according to ethnicity, histological, and anatomical sites. Results indicated that Arg72Pro is associated with higher susceptibility to cancer in some tumor sites, mainly hepatocarcinoma. For some tumor sites, quality of studies was associated with the size of genetic association, mainly in cervical, head and neck, gastric, and lung cancer. However, study quality did not explain the observed heterogeneity substantially. Meta-regression showed that ethnicity, allelic frequency and genotyping method were responsible for a substantial part of the heterogeneity observed. Our results suggest ethnicity and histological and anatomical sites may modulate the penetrance of Arg72Pro in cancer susceptibility. This meta-analysis denotes the importance for more studies with good quality and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of Arg72Pro in cancer.The tumor TP53 suppressor gene plays a pivotal role in protecting cells against genotoxic insults of endogenous or environmental agents, which orchestrate a diversity of pathways from transcriptional responses to apoptosis. 1,2 Although TP53 mutations are thought to be associated with carcinogenesis, 3,4 polymorphisms in TP53 seem to have a modest effect on cell phenotype, leading to different patterns of cancer susceptibility. 5 Among known TP53 polymorphisms, 6 Arg72Pro is the most studied, and in vitro assays have demonstrated a differential ability to trigger apoptosis 7 and susceptibility for degradation by the E6 protein of the HPV-16 virus. 8 However, in the epidemiologic field, even with a considerable number of reports analyzing the p53 Arg72Pro polymorphism and risk of cancer in case-control studies, results remain conflicting rather than conclusive. For breast cancer, for example, results vary from protective 9-12 to no association [13][14][15] or increase in risk. [16][17][18] Similar conflicting results are also observed for esophageal, 19-22 lung, 23-25 and colorectal cancer [26][27][28] and other cancer types. To better understand the role of Arg72-Pro, recent meta-analysis studies have been performed for different cancer types, such as lung, 29 gastric, 30 and cervical cancer. 31 However, each of these meta-analyses is restricted to a specif...

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“…Inaddition,thefactthatpublishedstudieshavebeenconductedonvariousChinese [11,16,21,[25][26][27],Caucasian [7,8,10,[12][13][14][15][17][18][19][20]22,24,[28][29][30][31][32][33]andmixed [9,23]populations renders the field even more challenging; indeed, our metaanalytical algorithm has revealed that race-specific effects often arise in meta-analyses concerning the association betweencancerriskandgeneticpolymorphisms [34][35][36][37][38][39][40].Specifically, concerning p53 Arg72Pro, the modulating effects of race have been demonstrated in various cancer types at a meta-analyticallevel.Inbreastcancer,theprotectiveeffectof the Pro allele was confined to European populations [3]; on thecontrary,theprotectiveeffectoftheArgallelewasconfinedtoAsiansubjectsingastriccancer [5].Asaresult,the in-depth examination of the association between p53 Arg72Propolymorphismstatusandcancerriskessentiallyencom-passestheevaluationofrace-specificeffects.…”

Section: Introductionmentioning

confidence: 99%

Association between p53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Meta-Analysis

et al. 2010

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Background: This meta-analysis on case-control studies aims to examine whether the p53 Arg72Pro polymorphism is associated with colorectal cancer risk, addressing also whether the effect of the polymorphism is modified by race. Patients and Methods: Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian, Chinese, and mixed populations. Meta-regression with publication year was also performed. Results: A total of 27 studies were eligible (7,414 cases and 9,872 controls); 19 of them were conducted on Caucasian populations (6282 cases and 7600 controls), 6 of them on Chinese populations (883 cases and 1,843 controls) and 2 on mixed populations (153 cases and 209 controls). No significant association was demonstrated in Caucasian, Chinese, or mixed populations. Interestingly, however, stratification by race in studies whose controls did not deviate from the Hardy-Weinberg equilibrium tended to reveal ORs pointing to a marginal protective effect of the Pro allele in Caucasians. Conclusions: The p53 codon 72 Arg72Pro status does not seem to be associated with colorectal cancer risk, although race-specific effects may not be ruled out. However, additional studies seem desirable, especially in Chinese populations.

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Genetic polymorphisms in TP53, nonsteroidal anti-inflammatory drugs and the risk of colorectal cancer: evidence for gene–environment interaction?

Abstract: These data suggest that the TP53 genotype may modify the influence of nonsteroidal anti-inflammatory drug use on the risk of colorectal cancer. A direct proof of functional analysis is warranted to confirm these findings.

Cited by 39 publications

References 40 publications

Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic

Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic

Arg72Pro TP53 polymorphism and cancer susceptibility: A comprehensive meta‐analysis of 302 case‐control studies

Association between p53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Meta-Analysis

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