Polymorphism at codon 72 of p53, human papillomavirus, and cervical cancer in South India.
OBJECTIVE
It has been suggested that host genetic factors play a role in human papillomavirus (HPV)-associated tumorigenesis, although the issue continues to be a focus of much debate. Previous studies have reported that a common polymorphism of the wild type p53 gene at codon 72 of exon 4 (Arg/Arg) is associated with a sevenfold increased risk of HPV-associated cancer compared to Arg/Pro and Pro/Pro polymorphisms. In vitro studies also suggested that the Arg/Arg polymorphism was much more susceptible to HPV 16 E6-mediated degradation as compared to other allelic forms. Subsequent studies published since this initial report indicated geographical differences with respect to the role of Arg/Arg polymorphism in increasing the risk of HPV-associated cervical cancer.


METHODS
In this study we analyzed leukocyte DNA from a total of 421 subjects for the Arg/Arg, Arg/Pro or Pro/Pro p53 polymorphisms at various stages of the cervical tumor progression spectrum, using allele-specific PCR. All subjects were from the Thiruvananthapuram District of South India. HPV genotyping was done for all subjects using either DNA extracted from cervical biopsies or exfoliated cervical cells. All subjects were grouped on the basis of both of cyto-pathology and HPV status.


RESULTS
The distribution of p53 genotypes was not significantly different in all study groups (HPV positive vs HPV negative and cases vs controls comparisons). Homozygosity for Arg/Arg was not associated with increased risk for cervical cancer.


CONCLUSIONS
We find no evidence for any association between homozygosity for p53 arginine with either cervical dysplasia, cervical carcinoma or HPV infection in the population from South India.
Pillai
M Radhakrishna
MR
Division of Laboratory Medicine, Regional Cancer Centre, Thiruvananthapuram 695011, India. mrpillai@vsnl.com
Sreevidya
S
S
Pollock
Brad H
BH
Jayaprakash
P G
PG
Herman
Brian
B
D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology; D003062:Codon; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007194:India; D027383:Papillomaviridae / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
D003062:Codon; D017931:DNA Primers; D004273:DNA, Neoplasm; D004279:DNA, Viral; D001120:Arginine