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Association of specific genotype and haplotype of p53 gene with cervical cancer in India

¹ Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700 032, India
² Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India

Correspondence to:
Dr S Roychoudhury
Human Genetics and Genomics Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700 032, India; susanta_rc{at}yahoo.co.in Background: The predictive value of codon 72 arginine homozygosity at the p53 gene for human papilloma virus associated cervical cancer risk remains inconclusive. It has also been proposed that the inheritance of specific germline haplotypes based on three biallelic polymorphisms of p53 (intron 3 16 bp duplication, codon 72 Bst UI (Arg/Pro), and intron 6 Nci I restriction fragment length polymorphism at nucleotide 13494) is a better predictor of various cancer risks.

Aims: To determine the genotype and haplotype frequency of these three p53 polymorphisms in 61 patients with cervical squamous cell carcinoma and 94 ethnically matched controls from the eastern region of India and estimate the risk, if any, of specific genotypes and haplotypes.

Methods: Samples were genotyped by polymerase chain reaction followed by variant specific restriction enzyme digestion. Haplotypes were estimated by the maximum likelihood method using the expectation maximisation algorithm.

Results: Genotype distributions of the three polymorphisms in patients and controls showed a good fit to the Hardy-Weinberg equilibrium. The p53 codon 72 arginine homozygous genotype was significantly over represented in patients compared with controls. Those with the homozygous arginine genotype exhibited a 2.59 fold higher risk of developing squamous cell carcinoma of the uterine cervix. A significant risk was also seen with a combination of two haplotypes, 1–2–1 and 1–2–2.

Conclusion: p53 codon 72 arginine homozygotes appear to be at greater risk of developing squamous cell carcinoma of the uterine cervix. The high risk haplotypes 1–2–1 and 1–2–2 also contain the arginine allele, further strengthening this conclusion.

Abbreviations: CI, confidence interval; df, degrees of freedom; HPV, human papillomavirus; nt, nucleotides; OR, odds ratio; PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism

Keywords: cervical cancer; genotype; haplotype; p53

This article has been cited by other articles:

				S Mitra, S Banerjee, C Misra, R K Singh, A Roy, A Sengupta, C K Panda, and S Roychoudhury Interplay between human papilloma virus infection and p53 gene alterations in head and neck squamous cell carcinoma of an Indian patient population J. Clin. Pathol., September 1, 2007; 60(9): 1040 - 1047. [Abstract] [Full Text] [PDF]