Modes of inheritance proposed for p53 codon 72

Dear Sir,

I have read with interest the recent report by Ding and coworkers on p53 codon 72 effects in susceptibility to hepatocellular carcinoma. ¹ The authors have compiled data from earlier investigations and conclude to a significant risk-lowering effect at codon 72, assuming a ‘dominant’ mode of inheritance. It is noteworthy that all other meta-analyses published on the same subject – including an analysis that appeared a year before the report by Ding et al. ¹ – obtain discrepant results, i.e. significant effects under a recessive model.^2–4 Ever since Gregor Mendel coined the term of dominant inheritance in 1866, ⁵ this implies that wild-type homozygous genotypes are contrasted with allele positivity (combining heterozygotes and homozygotes for the variant allele). The report by Ding et al., however, pools subjects homozygous for the variant allele with heterozygous subjects and thus posits recessive rather than dominant inheritance of codon 72. ¹ As for the quantitative assessment of risk-lowering effects with regard to ethnicity, more concerns emerge. It appears that Ding and coworkers have misinterpreted data by Anzola et al. ⁶ who screened for loss of heterozygosity in a subset of samples. Thus, the total number of Caucasian subjects is inflated by counting tissue samples rather than the respective number of participants. Taken together, the conclusion reached is hardly tenable in its present form.