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Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1840-7. doi: 10.1158/1055-9965.EPI-10-0156.

TP53 Arg72Pro polymorphism and colorectal cancer risk: a systematic review and meta-analysis.

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1
Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 35 Kneeland Street, Boston, MA 02111, USA. issa.dahabreh@tufts.edu

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 (P(interaction) = 0.03). Results were also inconsistent between different genotyping methods (P(interaction) = 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.

PMID:
20615891
DOI:
10.1158/1055-9965.EPI-10-0156
[Indexed for MEDLINE]
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