Abstract
The p53 tumour suppressor gene is inactivated in various types of human cancers, and has been implicated as an early event in several cancers. A p53 Pro/Arg polymorphism at exon 4 codon 72, has been suggested to be involved in susceptibility to cancers as well. Hence, in the current study, we investigated p53 exon 4 codon 72 polymorphism using Proline or Arginine specific primers from the peripheral blood cells (PBC) representing constitutional DNA from 72 oral cancer patients. PBC from 153 normal healthy individuals were used to determine the frequency of the p53 genotypes, Pro/Pro, Arg/Arg and Pro/Arg, in the Indian population. The frequency of distribution of genotypes in the normal healthy individuals was, Pro/Pro – 0.20 (31/153), Arg/Arg – 0.14 (22/153) and Pro/Arg – 0.65 (100/153); and in the oral cancer patients was, Pro/Pro – 0.19 (14/72), Arg/Arg – 0.08 (6/72) and Pro/Arg – 0.72 (52/72). Thus, we observed an equidistribution of the genotypes in normal control and oral cancer patients (χ2= 1.77, df = 2, 0.3 <P< 0.5). Further, DNA from corresponding tumours from the 72 oral cancer patients were examined for loss of heterozygosity in the p53 gene. Allelic loss was observed in 8 of 52 (15%) heterozygous informative oral cancer patients. Our data indicates an equidistribution of the genotypes and absence of over-representation of either Pro/Pro or Arg/Arg genotypes in the oral cancer patients as compared to the normal healthy controls. Hence, association of the p53 genotypes with susceptibility to oral cancer, was not observed. © 2001 Cancer Research Campaign http://www.bjcancer.com
Keywords: oral cancer, p53 gene, codon 72 polymorphism, loss of heterozygosity
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- Choi S. Y., Kahyo H. Effect of cigarette smoking and alcohol consumption in the aetiology of cancer of the oral cavity, pharynx and larynx. Int J Epidemiol. 1991 Dec;20(4):878–885. doi: 10.1093/ije/20.4.878. [DOI] [PubMed] [Google Scholar]
- D'Costa J., Saranath D., Dedhia P., Sanghvi V., Mehta A. R. Detection of HPV-16 genome in human oral cancers and potentially malignant lesions from India. Oral Oncol. 1998 Sep;34(5):413–420. doi: 10.1016/s1368-8375(98)00028-1. [DOI] [PubMed] [Google Scholar]
- Gillison M. L., Koch W. M., Capone R. B., Spafford M., Westra W. H., Wu L., Zahurak M. L., Daniel R. W., Viglione M., Symer D. E. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000 May 3;92(9):709–720. doi: 10.1093/jnci/92.9.709. [DOI] [PubMed] [Google Scholar]
- Gupta P. C., Bhonsle R. B., Murti P. R., Daftary D. K., Mehta F. S., Pindborg J. J. An epidemiologic assessment of cancer risk in oral precancerous lesions in India with special reference to nodular leukoplakia. Cancer. 1989 Jun 1;63(11):2247–2252. doi: 10.1002/1097-0142(19890601)63:11<2247::aid-cncr2820631132>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- Hamel N., Black M. J., Ghadirian P., Foulkes W. D. No association between P53 codon 72 polymorphism and risk of squamous cell carcinoma of the head and neck. Br J Cancer. 2000 Feb;82(4):757–759. doi: 10.1054/bjoc.1999.0993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jin X., Wu X., Roth J. A., Amos C. I., King T. M., Branch C., Honn S. E., Spitz M. R. Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype. Carcinogenesis. 1995 Sep;16(9):2205–2208. doi: 10.1093/carcin/16.9.2205. [DOI] [PubMed] [Google Scholar]
- Johnson N. W., Warnakulasuriya K. A. Epidemiology and aetiology of oral cancer in the United Kingdom. Community Dent Health. 1993 Jun;10 (Suppl 1):13–29. [PubMed] [Google Scholar]
- Kawajiri K., Nakachi K., Imai K., Watanabe J., Hayashi S. Germ line polymorphisms of p53 and CYP1A1 genes involved in human lung cancer. Carcinogenesis. 1993 Jun;14(6):1085–1089. doi: 10.1093/carcin/14.6.1085. [DOI] [PubMed] [Google Scholar]
- Largey J. S., Meltzer S. J., Yin J., Norris K., Sauk J. J., Archibald D. W. Loss of heterozygosity of p53 in oral cancers demonstrated by the polymerase chain reaction. Cancer. 1993 Mar 15;71(6):1933–1937. doi: 10.1002/1097-0142(19930315)71:6<1933::aid-cncr2820710602>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- Mahale A., Saranath D. Microsatellite alterations on chromosome 9 in chewing tobacco-induced oral squamous cell carcinomas from India. Oral Oncol. 2000 Mar;36(2):199–206. doi: 10.1016/s1368-8375(99)00083-4. [DOI] [PubMed] [Google Scholar]
- Murata M., Tagawa M., Kimura M., Kimura H., Watanabe S., Saisho H. Analysis of a germ line polymorphism of the p53 gene in lung cancer patients; discrete results with smoking history. Carcinogenesis. 1996 Feb;17(2):261–264. doi: 10.1093/carcin/17.2.261. [DOI] [PubMed] [Google Scholar]
- Raybaud-Diogène H., Tétu B., Morency R., Fortin A., Monteil R. A. p53 overexpression in head and neck squamous cell carcinoma: review of the literature. Eur J Cancer B Oral Oncol. 1996 May;32B(3):143–149. doi: 10.1016/0964-1955(95)00095-x. [DOI] [PubMed] [Google Scholar]
- Saranath D., Bhoite L. T., Deo M. G. Molecular lesions in human oral cancer: the Indian scene. Eur J Cancer B Oral Oncol. 1993 Apr;29B(2):107–112. doi: 10.1016/0964-1955(93)90031-9. [DOI] [PubMed] [Google Scholar]
- Saranath D., Panchal R. G., Nair R., Mehta A. R., Sanghavi V., Sumegi J., Klein G., Deo M. G. Oncogene amplification in squamous cell carcinoma of the oral cavity. Jpn J Cancer Res. 1989 May;80(5):430–437. doi: 10.1111/j.1349-7006.1989.tb02332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saranath D., Tandle A. T., Deo M. G., Mehta A. R., Sanghvi V. Loss of p53 gene as a biomarker of high risk oral leukoplakias. Indian J Biochem Biophys. 1997 Jun;34(3):266–273. [PubMed] [Google Scholar]
- Saranath D., Tandle A. T., Teni T. R., Dedhia P. M., Borges A. M., Parikh D., Sanghavi V., Mehta A. R. p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India. Oral Oncol. 1999 May;35(3):242–250. [PubMed] [Google Scholar]
- Själander A., Birgander R., Athlin L., Stenling R., Rutegård J., Beckman L., Beckman G. P53 germ line haplotypes associated with increased risk for colorectal cancer. Carcinogenesis. 1995 Jul;16(7):1461–1464. doi: 10.1093/carcin/16.7.1461. [DOI] [PubMed] [Google Scholar]
- Storey A., Thomas M., Kalita A., Harwood C., Gardiol D., Mantovani F., Breuer J., Leigh I. M., Matlashewski G., Banks L. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998 May 21;393(6682):229–234. doi: 10.1038/30400. [DOI] [PubMed] [Google Scholar]