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 haplo type 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 all ele (p = 0.005), MspI Al allele (p = 0.021) and the BstUI Al (Pro) all ele (p = 0.072) were found among the patients, with more pronounced di fferences in male patients (p = 0.003, 0.014 and 0.052, respectively). Haplotype frequencies and linkage disequilibria differed from those i n Caucasians. The differences between controls and patients, especiall y male patients, increased when the analysis was based on haplotypes. The lowest risk for nasopharyngeal cancer was associated with the hapl otype 16-bp Al, 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 includi ng the 16-bp A2 and MspI Al alleles with an odds ratio of 4.9 [95% con fidence 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 stu dy differ from those found in previous cancer association studies in C aucasians. This together with the fact that the intronic markers confe rred the highest risk figures suggest that the mechanism behind the ob served associations is linkage disequilibrium and not direct functiona l involvement of the codon 72 alleles.