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Preferential loss of heterozygosity at the rs1042522 locus of the tumor protein 53 gene (TP53) (Arg72Pro) is observed in several tumors. Genetic association studies in oncology often use tumor tissue rather than unaffected tissue for genotyping; in such cases, loss of heterozygosity at the TP53 locus could lead to differential misclassification and could bias estimates of association. We searched multiple databases (through March 8, 2011) for studies investigating the association of Arg72Pro with breast, lung, colorectal, ovarian, or endometrial cancer. Meta-analysis was performed with multilevel Bayesian models. Informative priors for the bias effect were derived from a meta-analysis of the same polymorphism in cervical cancer. Of 160 studies (68 breast, 42 lung, 26 colorectal, 16 ovarian, and 8 endometrial cancer), 22 used tumor tissue as the source of genotyping material for cases. Use of tumor tissue versus other sources of genotyping material was associated with an apparent protective effect of the proline allele (relative odds ratio = 0.78, 95% credible interval: 0.70, 0.88). The probability that use of tumor tissue induced bias was estimated to be higher than 99%. Use of tumor tissue as the source of genotyping material for cases is associated with significant bias in the estimate of the genetic effect in cancer genetic association studies.

american journal of epidemiology

Genotype Misclassification in Genetic Association Studies of the rs1042522 TP53 (Arg72Pro) Polymorphism: A Systematic Review of Studies of Breast, Lung, Colorectal, Ovarian, and Endometrial Cancer