Abstract
Storey et al. reply — These reports assess the frequency of the p53Arg allele in different populations and conclude that homozygous p53Arg is not a risk factor for cancer associated with human papilloma virus (HPV). The functional differences between the p53 isoforms that we have described1,2 provoked our initial epidemiological study. As we concluded then, it is crucial that investigations should be extended to different populations, and we are encouraged that such studies are underway.
Main
There are several potential reasons for the apparent discrepancies between our original study and those reported here. Our study comprised a smaller number of samples from a different population. In addition, rather than leukocyte DNA, we screened microdissected tumour material, in which we demonstrated that it was always the proline allele that was lost in cases of loss of heterozygosity, Furthermore, it is important to compare the different screening methodologies that have been used as this may also be a source of incorrect allelic assignment, which would lead to a bias towards a null hypothesis.
In such studies, the composition of the control population is a major factor affecting the outcome. We are now concentrating our efforts on populations with a higher frequency of the proline allele. Preliminary results from a Brazilian population strongly support our original observations. In addition, when the control population consists of cytologically normal but HPV-positive individuals, the association of the p53Arg allele with the risk of tumour development is greatly increased; a similar trend is reported here by Hildesheim et al. All of these factors need to be taken into consideration in any future studies of this polymorphism.
Continuing exploration of the differential effects of this polymorphism should further unravel the complexities of p53 function.
References
Storey, A. et al. Nature 393, 229–234 (1998).
Thomas, M. et al. (in the press).
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Storey, A., Thomas, M., Kalita, A. et al. p53 polymorphism and risk of cervical cancer. Nature 396, 532 (1998). https://doi.org/10.1038/25043
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DOI: https://doi.org/10.1038/25043
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