Infection of high risk human papillomaviruses (HPVs) specifically the types 16 and 18 has been strongly implicated in the development of
cervical cancer. The E6
oncoproteins of these high risk HPVs are known to bind and induce degradation of p53 tumour suppressor
protein through the
ubiquitin pathways. This degradation is controlled by a common polymorphism of the p53 gene encoding either a
proline or an
arginine at its
codon 72 in exon 4. Recently, it has been demonstrated that the presence of homozygous
arginine at
codon 72 renders p53 about seven times more susceptible to E6-mediated proteolytic degradation as well as to
cervical cancer than those with
proline homozygotes or
proline/
arginine heterozygotes. In India, prevalence of HPV as well as
cancers of the uterine cervix and the oral cavity are highest in the world. We have examined this allele-specific predisposition in cervical and
oral cancer which is associated with HPV as well as in a non-HPV-linked
cancer of the breast. We have carried out investigation in women comprising whole spectrum of cervical lesions with 128 HPV 16/18 positive and 35 HPV negative invasive cervical
carcinomas and 34 cases of HPV (16/18) positive and 16 HPV negative
cervical dysplasias (mild, moderate and severe) and 104 age-group-matched healthy women as controls. Additionally, we have analysed p53Arg-Pro polymorphism in 13 high risk HPV positive and 31 HPV negative
oral cancers along with 20 normal controls and 77 breast
cancers with 41 age-matched healthy controls. We observed more than two fold higher risk for homozygous
arginine (chi2 = 6.3, df = 2, p = 0.04; OR = 2.3; 95% CI: 1.08-5.16) for HPV 16/18-positive cervical
carcinomas when comparison was made only between HPV positive
cervical cancers and normal controls but most interestingly, no significant association either in the frequency of homozygous
arginine or
proline alleles or their heterozygotes could be observed when all the three groups i.e. HPV-positive, HPV-negative
cervical cancers and controls were considered simultaneously. No difference was also observed for either
arginine or
proline polymorphism between women with precancerous lesions of the uterine cervix carrying HPV 16/18
infection and controls. Similarly, increased risk of oral or
breast cancer could not be correlated with the polymorphism of
arginine/
proline allele. Thus the interaction between HPV
oncoproteins and the p53 gene polymorphism specifically, homozygous
arginine at
codon 72 appears to play no role in the development of either cervical or
oral cancer and also it can not serve as a
biomarker for early identification of cervical, oral or
breast cancer.