NDLI: Polymorphism of the p53 codon 72 arg/pro and the risk of HPV type 16/18-associated cervical and oral cancer in India

Content Provider	Springer Nature Link
Author	Katiyar, Sanjay Thelma, B.K. Murthy, N.S. Hedau, Suresh Jain, Neeraj Gopalkrishna, V. Husain, Syed Akhtar Das, Bhudev C.
Copyright Year	2003
Abstract	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 2 fold higher risk for homozygous arginine (χ$^{2}$ = 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.
Starting Page	117
Ending Page	124
Page Count	8
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	252
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	2003-01-01
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cardiology Medical Biochemistry Oncology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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