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Mutagenesis vol. 18 no. 4 pp. 377-385, July 2003
© 2003 UK Environmental Mutagen Society/Oxford University Press

TP53 polymorphisms and lung cancer risk: a systematic review and meta-analysis

A. Matakidou3,1,2, T. Eisen2 and R.S. Houlston1

1Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK and 2Cancer Research Unit, Section of Medicine, Royal Marsden Hospital, Downs Road, Sutton, UK

To examine the risk of lung cancer associated with the codon 72, intron 6 and intron 3 TP53 polymorphisms a meta-analysis of published case–control studies was undertaken. The principle outcome measure was the odds ratio (OR) for the risk of lung cancer using homozygosity of the ‘wild-type allele’ as the reference group. Data from 13 studies detailing the relationship between lung cancer and the codon 72 polymorphism of TP53 and three studies examining the intron 3 and 6 polymorphisms of TP53 were analysed. The ORs of lung cancer associated with the Pro-Pro and Pro-carrier genotypes of codon 72 were 1.18 [95% confidence interval (CI) 0.99–1.41] and 1.02 (95% CI 0.86–1.20), respectively. The ORs of lung cancer associated with homozygous and variant allele carrier genotypes of the intron 6 (MspI RFLP) polymorphism were 1.13 (95% CI 0.55–2.27) and 1.30 (95% CI 0.75–2.26) and of the intron 3 (16 bp duplication) polymorphism were 1.50 (95% CI 0.76–2.97) and 1.11 (95% CI 0.53–2.35), respectively. Although polymorphic variations in TP53 represent attractive candidate susceptibility alleles for lung cancer the results from this analysis provide little support for this hypothesis. Additional well-designed studies based on sample sizes commensurate with the detection of small genotypic risks may allow a more definitive conclusion.

3To whom correspondence should be addressed at Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK. Tel: +44 208 643 8901; Fax: +44 208 643 0257; Email: athenam{at}icr.ac.uk


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