Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
    • Progress and Priorities
    • Collections
      • COVID-19 & Cancer Resource Center
      • Disparities Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Informing Public Health Policy
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CEBP Focus Archive
    • Meeting Abstracts
    • Progress and Priorities
    • Collections
      • COVID-19 & Cancer Resource Center
      • Disparities Collection
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Informing Public Health Policy
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Research Articles

TP53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis

Issa J. Dahabreh, Helena Linardou, Peggy Bouzika, Vasileia Varvarigou and Samuel Murray
Issa J. Dahabreh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Helena Linardou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peggy Bouzika
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vasileia Varvarigou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samuel Murray
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1055-9965.EPI-10-0156 Published July 2010
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background: The TP53 rs1042522 polymorphism (c.215C>G, Arg72Pro) has been extensively investigated as a potential risk factor for colorectal cancer, but the results have thus far been inconclusive.

Methods: We searched multiple electronic databases to identify studies investigating the association between the Arg72Pro polymorphism and colorectal cancer. Individual study odds ratios (OR) and their confidence intervals were estimated using allele-frequency, recessive, and dominant genetic models. Summary ORs where estimated using random effects models.

Results: We identified 23 eligible case-control studies, investigating 6,514 cases and 9,334 controls. There was significant between-study heterogeneity for all genetic models. The control group in one of the studies was not in Hardy-Weinberg equilibrium; only three studies reported that genotyping was blinded to case/control status and five studies used tumor tissue for case genotyping. Overall, we did not identify any association between rs1042522 and colorectal cancer risk under an allele-frequency comparison (OR, 0.99; 95% confidence interval, 0.89–1.09). Likewise, no association was evident under dominant or recessive models. Studies using tumor tissue for case genotyping found a protective effect for the Pro allele, compared with studies using somatic DNA (Pinteraction = 0.03). Results were also inconsistent between different genotyping methods (Pinteraction = 0.03).

Conclusion: We did not identify an association between TP53 rs1042522 and colorectal cancer. Published results seem to be driven by technical artifacts rather than true biological effects.

Impact: Future genetic association studies should use more rigorous genotyping methods and avoid the use of tumor tissue as a source of DNA to prevent genotype misclassification due to loss of heterozygosity. Cancer Epidemiol Biomarkers Prev; 19(7); 1840–7. ©2010 AACR.

Introduction

Colorectal cancer is the third most common type of cancer in the United States and is responsible for approximately 50,000 deaths per year (1). Family-based studies have suggested that the disease has a significant genetic component, with a large twin study conducted in Scandinavian countries suggesting that as many as 35% of colorectal cancers may be due to inherited susceptibility (2). However, the recognized Mendelian predisposition syndromes, such as hereditary nonpolyposis colorectal cancer and adenomatus polyposis coli, account for less than 5% of the overall incidence of colorectal cancer (3). Therefore, common, low-penetrance polymorphisms may confer a substantial part of the genetic risk, but given that the estimated effect of each polymorphism is expected to be small, large studies are necessary to reduce the size-related uncertainty of effects and provide robust evidence of association.

The TP53 gene, located at 17p13, is a prototypical tumor suppressor gene encoding a 53-kDa protein (p53) with important functions in cell cycle control, apoptosis, and maintenance of DNA integrity (4-6). The importance of p53 in cell cycle regulation (via gene transcription) and DNA integrity is such that it has been called the “guardian of the genome” (7). The function of p53 is to reduce the incidence of cancers by mediating apoptosis in cells that have activated oncogenic pathways. Similarly, DNA damage or genotoxic stress may cause the induction of p53, leading to growth arrest or apoptosis (8). Germ-line mutations in TP53 are known to cause a number of recognized human cancers including Li-Fraumeni syndrome (9). When TP53 itself is not genetically inactivated, other mechanisms, such as loss of heterozygosity by deletion of the 17p locus or gene methylation, may contribute to reduced p53 activity (10-15). The polymorphic nature of the TP53 gene and its central role in cell cycle regulation have highlighted it as a good potential candidate susceptibility gene for colorectal cancer. Although several TP53 polymorphisms have been investigated as risk factors for cancer, by far the most extensively investigated is a nonsynonymous polymorphism in a proline-rich domain located in exon 4, where a cytosine (C; variant allele) for guanine (G) substitution results in the substitution of proline (Pro) for arginine (Arg) at codon 72 of the p53 protein (Arg72Pro, refSNP no. rs1042522; ref. 16). Various lines of evidence indicate that these two alleles differ in their capacities to induce target gene transcription, their interaction with p73, their targeting of the proteasome, and their susceptibility to degradation by human papillomavirus E6 protein (17-20). They are also recognized as modulating apoptosis at differing rates (21).

Several epidemiologic studies have addressed the influence of this polymorphism on cancer risk for most common cancer types, including colorectal cancer; however, small sample sizes and deficiencies in study design have contributed to conflicting results (22-26). To offer a comprehensive evaluation of the potential association of this polymorphism with colorectal cancer risk, we conducted a systematic review and meta-analysis of candidate genetic association studies.

Materials and Methods

Study eligibility and data extraction

We sought to identify genetic association studies published before July 31, 2009, investigating the association between the rs1042522 polymorphism located within the TP53 gene and colorectal cancer, using computer-based searches (last search: July 31, 2009) of MEDLINE (PubMed), the Human Genome Epidemiology Network (HuGE Net) Literature Finder, and the NIH Genetic Association Database (27), using keywords related to the TP53 gene and colorectal cancer (the full search strategy is available from the authors on request). Additionally, we searched two TP53-specific databases that collect information related to TP53 polymorphisms: the IARC TP53 database (28) and the p53 website (29). We also hand-searched the reference lists for all retrieved studies and relevant review articles, as well as journals known to publish studies relevant to the topic.

Studies using an analytic design (case-control, nested case-control, or cohort) and employing validated genotyping methods to examine the frequency of rs1042522 among colorectal cancer patients and controls were eligible for inclusion. Family-based studies were not considered eligible owing to different design considerations. Studies that included patients known to have hereditary colorectal cancer syndromes, such as nonpolyposis colorectal cancer or familial adenomatous polyposis, were excluded. If studies reported on mixed populations of syndromic and sporadic colorectal cancer, we only used the genotype information for patients with sporadic disease (when available). We only considered studies published in English.

The following information was abstracted from each study: first author, journal, year of publication, study design, matching, ethnicity of participants, definition and numbers of cases and controls, DNA extraction and genotyping methods, source of genetic material for genotyping cases, frequency of genotypes, anatomic location of the tumor (colon versus rectum), and the number of cases and controls for each TP53 genotype. Data extraction was done independently by two reviewers (I.J.D. and V.V.) and discrepancies were resolved by consensus including a third reviewer (S.M.).

Evidence synthesis

For our main analysis, we compared allele frequencies (the proline-encoding allele C versus the arginine-encoding allele G) between cases and controls. We also evaluated a recessive (CC versus CG+GG) and a dominant model (CC+CG versus GG) for the C allele. All associations were presented as odds ratios (OR) with their corresponding 95% confidence interval (95% CI). Between-study heterogeneity was tested using the χ2-based Q-statistic and was considered statistically significant at P < 0.1 (30). Between-study inconsistency was quantified using the I2 statistic (31). A pooled OR was estimated based on the individual study ORs using random-effects (DerSimonian and Laird) models (32). Cumulative meta-analysis was carried out to evaluate the trend of the random-effects OR over time (33).

Cancer subtype (colon versus rectum), participant ethnicity (individuals of White ancestry versus East Asian), Hardy-Weinberg equilibrium (HWE) in the control group, matching of cases and controls, genotyping quality control (repeat genotyping of a random selection of samples), blinded genotyping (genotyping by individuals blinded to the case/control status of each individual versus lack of blinding or no mention of blinding), and source of DNA for cases (use of tumor tissue obtained during surgery versus blood/normal tissue) were prespecified as characteristics for assessment of heterogeneity by subgroup analysis. When a study explicitly stated that pathologic examination was used to select healthy tissue obtained by surgery, we considered the study along with studies that used blood samples, given the high sensitivity and specificity of pathologic diagnosis for discriminating healthy and cancer tissues. We also performed sensitivity analysis by excluding such studies.

Assessment of bias

The differential magnitude of effect in large versus small studies was assessed using the Harbord modification of the Egger test (34, 35). A test for interaction was used to compare the results of the first study with the pooled estimate of all subsequent studies and to compare pooled effect estimates between studies (36). The distribution of the genotypes in the control group was tested for HWE using an exact test (37). Studies with controls not in HWE were subjected to a sensitivity analysis in which the effect of excluding specific studies was examined. Analyses were performed using Stata (version 11/SE, Stata Corp.) and statistical significance was defined as a two-sided P value <0.05 for all tests except those for heterogeneity.

Results

Our initial search identified 5,035 studies, of which 62 were considered potentially eligible for inclusion in this review and were retrieved in full text. Of those, 37 were excluded (9 did not include colorectal cancer patients, 8 did not include control groups, 8 did not assess the polymorphism of interest, 5 were not published in English, 4 included patients with hereditary colorectal cancer syndromes, 2 were preclinical studies, and 1 was an editorial) and 25 were considered eligible for the meta-analysis (references to excluded studies are available on request). Of those, one study did not provide extractable data (38) and one used an unconventional genotyping method (DNA pooling; ref. 39) and was included only in sensitivity analyses. For the main analysis, 23 studies were considered eligible, of which one provided data only for the recessive model (40); the first was published in 1991 and the last in 2009 (40-62). Detailed study characteristics are presented in Table 1 and Supplementary Table S1. In total, 23 studies investigated 6,514 colorectal cancer cases and 9,334 controls for the Arg72Pro polymorphism (mean number of cases, 283; median, 115; min, 53; max, 2,558). Sixteen studies had healthy individuals as controls, and seven studies matched cases and controls (all for age, and five of those for gender). Nine studies used some form of genotyping quality control and only three reported that genotyping was blinded to the case-control status of participants. In one study, the distribution of the genotypes in the control group was not in HWE (Fisher's exact test, P < 0.05). Five studies used tumor tissue obtained during surgery for determining the case genotype.

View this table:
  • View inline
  • View popup
Table 1.

Characteristics of eligible studies

The overall analysis investigating the association between C allele and risk of colorectal cancer relative to the G allele (C versus G) revealed significant between-study heterogeneity (PQ < 0.001; I2 = 63%) and the random-effects OR was nonsignificant (OR, 0.99; 95% CI, 0.89–1.09; P = 0.80; Fig. 1). Moreover, the recessive model for the C allele (CC versus CG+GG) showed moderate heterogeneity (P = 0.02, I2 = 44%) and no evidence of an association (OR, 1.01; 95% CI, 0.84–1.21; Supplementary Fig. S1A). Similarly, the dominant model for the C allele (CC+CG versus GG) showed significant heterogeneity (P < 0.001, I2 = 65%) and the random-effects OR was nonsignificant (OR, 1.00; 95% CI, 0.88–1.15; Supplementary Fig. S1B).

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Forest plot for the allele-frequency comparison (C versus G) using random effects calculations. Each study is shown by the point estimate of the OR (square proportional to the weight of each study) and 95% CI (extending lines). Studies are listed by year of publication.

In cumulative meta-analysis of allele-frequency contrasts, the pooled OR has remained centered on 1 over time, indicating that rs1042522 is an unlikely risk variant for colorectal cancer (Supplementary Fig. S2).

Potential for bias

There was no evidence of a differential magnitude of effects in large versus small studies (Harbord/Egger test P > 0.5 for all genetic contrasts). In addition, there was no significant difference between the OR of the first study versus the pooled random-effects OR of all subsequent studies under any genetic model, and between-study heterogeneity remained significant after excluding the first study from all analyses (PQ < 0.001 for the allele-frequency and dominant models, and PQ = 0.02 for the recessive genetic model).

Subgroup and sensitivity analyses

Overall, we did not find evidence of effect heterogeneity between studies that reported the use of quality control for genotyping or those where genotyping was performed blinded to the case/control status of participants, compared with those that did not. Although few studies stratified cases into colon and rectal cancer subgroups, the effect of rs1042522 was null in both. Studies using RFLP genotyping methods suggested that the Pro allele was associated with an increased risk of colorectal cancer (OR, 1.12; 95% CI, 0.96–1.30), compared with studies using alternative genotyping methods (OR, 0.91; 95% CI, 0.82–1.01). The difference was statistically significant (Pinteraction = 0.03). Furthermore, the ORs from studies using tumor tissue for case genotyping showed a protective effect for the Pro allele (OR, 0.75; 95% CI, 0.60–0.94). In contrast, studies using blood/normal tissue did not detect an association (OR, 1.04; 95% CI, 0.94–1.15); this difference was statistically significant (Pinteraction = 0.03). In addition, studies of East Asian populations seemed to produce more exaggerated effect sizes compared with studies in Caucasian populations (Pinteraction = 0.03). Finally, inclusion of the study that used DNA pooling also did not affect the results under any genetic model (data not shown; ref. 39). Table 2 summarizes the results of subgroup analysis for the allele-frequency comparison. Supplementary Table S2 summarizes the results of subgroup analyses using different genetic models.

View this table:
  • View inline
  • View popup
Table 2.

Subgroup and sensitivity analyses

Discussion

Colorectal cancer is estimated to have a significant heritable component, which is not completely accounted for by the high-penetrance mutations responsible for the known Mendelian colorectal cancer predisposition syndromes (3). The TP53 rs1042522 polymorphism, one of the most widely investigated polymorphisms in genetic epidemiology, has been considered a good candidate genetic risk factor for many cancers (23). This meta-analysis, based on 6,514 cases and 9,334 controls, shows that this polymorphism is an unlikely risk factor for colorectal cancer. Our results are supportive of the findings of the largest study of this polymorphism in colorectal cancer conducted to date by a collaborative effort of British investigators (61), which did not identify an association between rs1042522 and colorectal cancer. Most importantly, several potential factors that may lead to bias seem to be active in this field. For example, only three studies specifically mentioned that genotyping was blinded to case/control status, and only nine studies implemented some form of genotyping quality control.

Subgroup analysis showed that the ORs from studies of East Asian individuals were exaggerated compared with those investigating Caucasian individuals (Pinteraction = 0.03). Most likely, this is a spurious finding and does not represent a true biological difference (63, 64). Furthermore, use of RFLP methods for genotyping produced significantly different results compared with other genotyping methods (Pinteraction = 0.03). This discrepancy between genotyping methods highlights the need for implementing rigorous quality control procedures in future studies, but it is unclear whether the interaction of genotyping method and genetic effect is due to bias in calling uncertain results, or if use of RFLP methods is a surrogate for study quality in general (48). In addition, subgroup analysis revealed that the ORs from studies using cancer tissue for genotyping the cases were significantly (P = 0.03) different from the pooled point estimate of studies using blood/normal tissue. In general, use of tumor-derived DNA for determining the constitutional genotype is discouraged because multiple deletional somatic events that occur in tumor cells early in the carcinogenetic process may skew the overall results. Loss of heterozygosity often occurs in colorectal cancer, in many cases involving large genomic regions. There is also evidence that allelic loss at the TP53 locus is nonrandom, and that tumor cells preferentially retain the Arg allele, in different cancer types (19, 57, 65, 66). Regarding colorectal cancer in particular, studies in heterozygous individuals have shown that there is a preferential retention of the Arg allele that may cause genotype misclassification (57). This misclassification would tend to bias the results of genetic association studies toward a detrimental effect of the Arg allele (i.e., a spurious protective effect for the Pro allele). Interestingly, similar results were reached in a recent pooled analysis of individual patient data from 49 studies in cervical cancer (24). Overall, laboratory artifacts, rather than true biological effects, seem to drive the observed associations of Arg72Pro with colorectal cancer.

It should be noted that the pooled effect estimate based on studies using appropriate DNA sources is in itself not accurate enough to exclude the possibility of a small effect of the rs1042522 polymorphism on colorectal cancer risk, indicating that further research may be necessary to provide conclusive evidence for this variant. Another important limitation of the existing literature is the lack of information about potential gene-gene or gene-environment interactions. Given that the role of several environmental factors in the pathogenesis of colorectal cancer is established, further research should be performed in this direction.

In conclusion, this systematic review and meta-analysis of genetic association studies shows that TP53 Arg72Pro is unlikely to be a major risk factor for colorectal cancer. Several sources of bias, including the use of inappropriate genotyping material and the lack of quality control, need to be addressed in the design of future studies.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

Grant Support: I.J. Dahabreh was supported by a research fellowship provided by the “Maria P. Lemos” Foundation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Received February 9, 2010.
  • Revision received April 25, 2010.
  • Accepted April 29, 2010.

References

  1. ↵
    1. Jemal A,
    2. Siegel R,
    3. Ward E,
    4. Hao Y,
    5. Xu J,
    6. Thun MJ
    . Cancer statistics. CA Cancer J Clin 2009;59:225–49.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Lichtenstein P,
    2. Holm NV,
    3. Verkasalo PK,
    4. et al
    . Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000;343:78–85.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Calvert PM,
    2. Frucht H
    . The genetics of colorectal cancer. Ann Intern Med 2002;137:603–12.
    OpenUrlCrossRefPubMed
  4. ↵
    1. Levine AJ
    . p53, the cellular gatekeeper for growth and division. Cell 1997;88:323–31.
    OpenUrlCrossRefPubMed
    1. Sager R
    . Tumor suppressor genes: the puzzle and the promise. Science 1989;246:1406–12.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Xu H,
    2. el-Gewely MR
    . P53-responsive genes and the potential for cancer diagnostics and therapeutics development. Biotechnol Annu Rev 2001;7:131–64.
    OpenUrlCrossRefPubMed
  6. ↵
    1. Lane DP
    . Cancer. p53, guardian of the genome. Nature 1992;358:15–6.
    OpenUrlCrossRefPubMed
  7. ↵
    1. Meek DW
    . The p53 response to DNA damage. DNA Repair (Amst) 2004;3:1049–56.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Frebourg T,
    2. Friend SH
    . Cancer risks from germline p53 mutations. J Clin Invest 1992;90:1637–41.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Hollstein M,
    2. Sidransky D,
    3. Vogelstein B,
    4. Harris CC
    . p53 mutations in human cancers. Science 1991;253:49–53.
    OpenUrlAbstract/FREE Full Text
    1. Gomez-Lazaro M,
    2. Fernandez-Gomez FJ,
    3. Jordan J
    . p53: twenty five years understanding the mechanism of genome protection. J Physiol Biochem 2004;60:287–307.
    OpenUrlPubMed
    1. Iacopetta B
    . TP53 mutation in colorectal cancer. Hum Mutat 2003;21:271–6.
    OpenUrlCrossRefPubMed
    1. Soong R,
    2. Powell B,
    3. Elsaleh H,
    4. et al
    . Prognostic significance of TP53 gene mutation in 995 cases of colorectal carcinoma. Influence of tumour site, stage, adjuvant chemotherapy and type of mutation. Eur J Cancer 2000;36:2053–60.
    OpenUrlCrossRefPubMed
    1. Delattre O,
    2. Olschwang S,
    3. Law DJ,
    4. et al
    . Multiple genetic alterations in distal and proximal colorectal cancer. Lancet 1989;2:353–6.
    OpenUrlCrossRefPubMed
  10. ↵
    1. Baker SJ,
    2. Fearon ER,
    3. Nigro JM,
    4. et al
    . Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 1989;244:217–21.
    OpenUrlAbstract/FREE Full Text
  11. ↵
    1. Matlashewski GJ,
    2. Tuck S,
    3. Pim D,
    4. Lamb P,
    5. Schneider J,
    6. Crawford LV
    . Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol 1987;7:961–3.
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Thomas M,
    2. Kalita A,
    3. Labrecque S,
    4. Pim D,
    5. Banks L,
    6. Matlashewski G
    . Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol 1999;19:1092–100.
    OpenUrlAbstract/FREE Full Text
    1. Irwin MS
    . Family feud in chemosensitvity: p73 and mutant p53. Cell Cycle 2004;3:319–23.
    OpenUrlPubMed
  13. ↵
    1. Marin MC,
    2. Jost CA,
    3. Brooks LA,
    4. et al
    . A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. Nat Genet 2000;25:47–54.
    OpenUrlCrossRefPubMed
  14. ↵
    1. Storey A,
    2. Thomas M,
    3. Kalita A,
    4. et al
    . Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 1998;393:229–34.
    OpenUrlCrossRefPubMed
  15. ↵
    1. Dumont P,
    2. Leu JI,
    3. Della Pietra AC III,
    4. George DL,
    5. Murphy M
    . The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 2003;33:357–65.
    OpenUrlCrossRefPubMed
  16. ↵
    1. Zhou Y,
    2. Li N,
    3. Zhuang W,
    4. et al
    . P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature. Int J Cancer 2007;121:1481–6.
    OpenUrlCrossRefPubMed
  17. ↵
    1. Whibley C,
    2. Pharoah PD,
    3. Hollstein M
    . p53 polymorphisms: cancer implications. Nat Rev Cancer 2009;9:95–107.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Klug SJ,
    2. Ressing M,
    3. Koenig J,
    4. et al
    . TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies. Lancet Oncol 2009;10:772–84.
    OpenUrlCrossRefPubMed
    1. Dai S,
    2. Mao C,
    3. Jiang L,
    4. Wang G,
    5. Cheng H
    . P53 polymorphism and lung cancer susceptibility: a pooled analysis of 32 case-control studies. Hum Genet 2009;125:633–8.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Chen J,
    2. Etzel CJ,
    3. Amos CI,
    4. et al
    . Genetic variants in the cell cycle control pathways contribute to early onset colorectal cancer in Lynch syndrome. Cancer Causes Control 2009;20:1769–77.
    OpenUrlPubMed
  20. ↵
    Available from: http://geneticassociationdb.nih.gov/; last accessed: July 31, 2009.
  21. ↵
    Available from: http://www-p53.iarc.fr/; last accessed: July 31, 2009.
  22. ↵
    Available from: http://p53.free.fr/; last accessed: July 31, 2009.
  23. ↵
    1. Cochran W
    . The combination of estimates from different experiments. Biometrics 1954;10:101–29.
    OpenUrlCrossRef
  24. ↵
    1. Higgins JP,
    2. Thompson SG,
    3. Deeks JJ,
    4. Altman DG
    . Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.
    OpenUrlFREE Full Text
  25. ↵
    1. DerSimonian R,
    2. Laird N
    . Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88.
    OpenUrlCrossRefPubMed
  26. ↵
    1. Lau J,
    2. Schmid CH,
    3. Chalmers TC
    . Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care. J Clin Epidemiol 1995;48:45–57; discussion 9–60.
    OpenUrlCrossRefPubMed
  27. ↵
    1. Egger M,
    2. Davey Smith G,
    3. Schneider M,
    4. Minder C
    . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–34.
    OpenUrlAbstract/FREE Full Text
  28. ↵
    1. Harbord RM,
    2. Egger M,
    3. Sterne JA
    . A modified test for small-study effects in meta-analyses of controlled trials with binary end points. Stat Med 2006;25:3443–57.
    OpenUrlCrossRefPubMed
  29. ↵
    1. Altman DG,
    2. Bland JM
    . Interaction revisited: the difference between two estimates. BMJ 2003;326:219.
    OpenUrlFREE Full Text
  30. ↵
    1. Trikalinos TA,
    2. Salanti G,
    3. Khoury MJ,
    4. Ioannidis JP
    . Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations. Am J Epidemiol 2006;163:300–9.
    OpenUrlAbstract/FREE Full Text
  31. ↵
    1. Goodman JE,
    2. Mechanic LE,
    3. Luke BT,
    4. Ambs S,
    5. Chanock S,
    6. Harris CC
    . Exploring SNP-SNP interactions and colon cancer risk using polymorphism interaction analysis. Int J Cancer 2006;118:1790–7.
    OpenUrlCrossRefPubMed
  32. ↵
    1. Gaustadnes M,
    2. Orntoft TF,
    3. Jensen JL,
    4. Torring N
    . Validation of the use of DNA pools and primer extension in association studies of sporadic colorectal cancer for selection of candidate SNPs. Hum Mutat 2006;27:187–94.
    OpenUrlCrossRefPubMed
  33. ↵
    1. Mammano E,
    2. Belluco C,
    3. Bonafe M,
    4. et al
    . Association of p53 polymorphisms and colorectal cancer: modulation of risk and progression. Eur J Surg Oncol 2009;35:415–9.
    OpenUrlPubMed
    1. Cao Z,
    2. Song JH,
    3. Park YK,
    4. et al
    . The p53 codon 72 polymorphism and susceptibility to colorectal cancer in Korean patients. Neoplasma 2009;56:114–8.
    OpenUrlCrossRefPubMed
    1. Csejtei A,
    2. Tibold A,
    3. Varga Z,
    4. et al
    . GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer. Anticancer Res 2008;28:1917–22.
    OpenUrlAbstract/FREE Full Text
    1. Dakouras A,
    2. Nikiteas N,
    3. Papadakis E,
    4. et al
    . P53Arg72 homozygosity and its increased incidence in left-sided sporadic colorectal adenocarcinomas, in a Greek-Caucasian population. Anticancer Res 2008;28:1039–43.
    OpenUrlAbstract/FREE Full Text
    1. Gemignani F,
    2. Moreno V,
    3. Landi S,
    4. et al
    . A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA. Oncogene 2004;23:1954–6.
    OpenUrlCrossRefPubMed
    1. Grünhage F,
    2. Jungck M,
    3. Lamberti C,
    4. et al
    . Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes. Int J Colorectal Dis 2008;23:147–54.
    OpenUrlCrossRefPubMed
    1. Hamajima N,
    2. Matsuo K,
    3. Suzuki T,
    4. et al
    . No associations of p73 G4C14-to-A4T14 at exon 2 and p53 Arg72Pro polymorphisms with the risk of digestive tract cancers in Japanese. Cancer Lett 2002;181:81–5.
    OpenUrlCrossRefPubMed
    1. Kawajiri K,
    2. Nakachi K,
    3. Imai K,
    4. Watanabe J,
    5. Hayashi S
    . Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis 1993;14:1085–9.
    OpenUrlAbstract/FREE Full Text
  34. ↵
    1. Koushik A,
    2. Tranah GJ,
    3. Ma J,
    4. et al
    . p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer. Int J Cancer 2006;119:1863–8.
    OpenUrlCrossRefPubMed
    1. Kruger S,
    2. Bier A,
    3. Engel C,
    4. et al
    . The p53 codon 72 variation is associated with the age of onset of hereditary non-polyposis colorectal cancer (HNPCC). J Med Genet 2005;42:769–73.
    OpenUrlAbstract/FREE Full Text
    1. Langerod A,
    2. Bukholm IR,
    3. Bregard A,
    4. et al
    . The TP53 codon 72 polymorphism may affect the function of TP53 mutations in breast carcinomas but not in colorectal carcinomas. Cancer Epidemiol Biomarkers Prev 2002;11:1684–8.
    OpenUrlAbstract/FREE Full Text
    1. Murata M,
    2. Tagawa M,
    3. Kimura M,
    4. Kimura H,
    5. Watanabe S,
    6. Saisho H
    . Analysis of a germ line polymorphism of the p53 gene in lung cancer patients; discrete results with smoking history. Carcinogenesis 1996;17:261–4.
    OpenUrlAbstract/FREE Full Text
    1. Olschwang S,
    2. Laurent-Puig P,
    3. Vassal A,
    4. Salmon RJ,
    5. Thomas G
    . Characterization of a frequent polymorphism in the coding sequence of the Tp53 gene in colonic cancer patients and a control population. Hum Genet 1991;86:369–70.
    OpenUrlPubMed
    1. Perez LO,
    2. Abba MC,
    3. Dulout FN,
    4. Golijow CD
    . Evaluation of p53 codon 72 polymorphism in adenocarcinomas of the colon and rectum in La Plata, Argentina. World J Gastroenterol 2006;12:1426–9.
    OpenUrlPubMed
    1. Perfumo C,
    2. Bonelli L,
    3. Menichini P,
    4. et al
    . Increased risk of colorectal adenomas in Italian subjects carrying the p53 PIN3 A2–72 haplotype. Digestion 2006;74:228–35.
    OpenUrlCrossRefPubMed
    1. Polakova V,
    2. Pardini B,
    3. Naccarati A,
    4. et al
    . Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. Hum Mutat 2009;30:661–8.
    OpenUrlCrossRefPubMed
    1. Sayhan N,
    2. Yazici H,
    3. Budak M,
    4. Bitisik O,
    5. Dalay N
    . P53 codon 72 genotypes in colon cancer. Association with human papillomavirus infection. Res Commun Mol Pathol Pharmacol 2001;109:25–34.
    OpenUrlPubMed
  35. ↵
    1. Schneider-Stock R,
    2. Mawrin C,
    3. Motsch C,
    4. et al
    . Retention of the arginine allele in codon 72 of the p53 gene correlates with poor apoptosis in head and neck cancer. Am J Pathol 2004;164:1233–41.
    OpenUrlCrossRefPubMed
    1. Sjalander A,
    2. Birgander R,
    3. Athlin L,
    4. et al
    . P53 germ line haplotypes associated with increased risk for colorectal cancer. Carcinogenesis 1995;16:1461–4.
    OpenUrlAbstract/FREE Full Text
    1. Sotamaa K,
    2. Liyanarachchi S,
    3. Mecklin JP,
    4. et al
    . p53 codon 72 and MDM2 SNP309 polymorphisms and age of colorectal cancer onset in Lynch syndrome. Clin Cancer Res 2005;11:6840–4.
    OpenUrlAbstract/FREE Full Text
    1. Tan XL,
    2. Nieters A,
    3. Hoffmeister M,
    4. Beckmann L,
    5. Brenner H,
    6. Chang-Claude J
    . Genetic polymorphisms in TP53, nonsteroidal anti-inflammatory drugs and the risk of colorectal cancer: evidence for gene-environment interaction? Pharmacogenet Genomics 2007;17:639–45.
    OpenUrlCrossRefPubMed
  36. ↵
    1. Webb EL,
    2. Rudd MF,
    3. Sellick GS,
    4. et al
    . Search for low penetrance alleles for colorectal cancer through a scan of 1467 non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort analysis of 14 704 first-degree relatives. Hum Mol Genet 2006;15:3263–71.
    OpenUrlAbstract/FREE Full Text
  37. ↵
    1. Zhu ZZ,
    2. Wang AZ,
    3. Jia HR,
    4. et al
    . Association of the TP53 codon 72 polymorphism with colorectal cancer in a Chinese population. Jpn J Clin Oncol 2007;37:385–90.
    OpenUrlAbstract/FREE Full Text
  38. ↵
    1. Ioannidis JP,
    2. Ntzani EE,
    3. Trikalinos TA
    . “Racial” differences in genetic effects for complex diseases. Nat Genet 2004;36:1312–8.
    OpenUrlCrossRefPubMed
  39. ↵
    1. Pan Z,
    2. Trikalinos TA,
    3. Kavvoura FK,
    4. Lau J,
    5. Ioannidis JP
    . Local literature bias in genetic epidemiology: an empirical evaluation of the Chinese literature. PLoS Med 2005;2:e334.
    OpenUrlCrossRefPubMed
  40. ↵
    1. Brooks LA,
    2. Tidy JA,
    3. Gusterson B,
    4. et al
    . Preferential retention of codon 72 arginine p53 in squamous cell carcinomas of the vulva occurs in cancers positive and negative for human papillomavirus. Cancer Res 2000;60:6875–7.
    OpenUrlAbstract/FREE Full Text
  41. ↵
    1. Tada M,
    2. Furuuchi K,
    3. Kaneda M,
    4. et al
    . Inactivate the remaining p53 allele or the alternate p73? Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants. Carcinogenesis 2001;22:515–7.
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Cancer Epidemiology Biomarkers & Prevention: 19 (7)
July 2010
Volume 19, Issue 7
  • Table of Contents
  • Table of Contents (PDF)

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Epidemiology, Biomarkers & Prevention article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
TP53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis
(Your Name) has forwarded a page to you from Cancer Epidemiology, Biomarkers & Prevention
(Your Name) thought you would be interested in this article in Cancer Epidemiology, Biomarkers & Prevention.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
TP53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis
Issa J. Dahabreh, Helena Linardou, Peggy Bouzika, Vasileia Varvarigou and Samuel Murray
Cancer Epidemiol Biomarkers Prev July 1 2010 (19) (7) 1840-1847; DOI: 10.1158/1055-9965.EPI-10-0156

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
TP53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis
Issa J. Dahabreh, Helena Linardou, Peggy Bouzika, Vasileia Varvarigou and Samuel Murray
Cancer Epidemiol Biomarkers Prev July 1 2010 (19) (7) 1840-1847; DOI: 10.1158/1055-9965.EPI-10-0156
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Urinary Melatonin in Relation to Breast Cancer Risk
  • Endometrial Cancer and Ovarian Cancer Cross-Cancer GWAS
  • Risk Factors of Subsequent CNS Tumor after Pediatric Cancer
Show more Research Articles
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Epidemiology, Biomarkers & Prevention

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Epidemiology, Biomarkers & Prevention
eISSN: 1538-7755
ISSN: 1055-9965

Advertisement