p53 polymorphisms and haplotypes in nasopharyngeal cancer.

Three p53 DNA polymorphisms (BstUI and MspI RFLPs in exon 4 and intron 6, respectively, and a 16-bp duplication in intron 3) and their haplotype combinations were studied in 73 patients (61 males and 12 females) with nasopharyngeal cancer and 105 healthy controls from the Guizhou province in southern China. Increased frequencies of the 16-bp A2 allele (p = 0.005), MspI A1 allele (p = 0.021) and the BstUI A1 (Pro) allele (p = 0.072) were found among the patients, with more pronounced differences in male patients (p = 0.003, 0.014 and 0.052, respectively). Haplotype frequencies and linkage disequilibria differed from those in Caucasians. The differences between controls and patients, especially male patients, increased when the analysis was based on haplotypes. The lowest risk for nasopharyngeal cancer was associated with the haplotype 16-bp A1, BstUI A2, MspI A2 (1-2-2). A somewhat higher risk was observed in the 1-1-2 haplotype (replacing the Arg with a Pro allele). The highest risk was, however, found in the rare combinations including the 16-bp A2 and MspI A1 alleles with an odds ratio of 4.9 [95% confidence interval (CI) = 1.8-13.2] in all patients and 5.4 (95% CI = 2.0-14.8) in male patients. The haplotype associations found in this study differ from those found in previous cancer association studies in Caucasians. This together with the fact that the intronic markers conferred the highest risk figures suggest that the mechanism behind the observed associations is linkage disequilibrium and not direct functional involvement of the codon 72 alleles.