Interferon-alpha and p53 alleles involved in nasopharyngeal carcinoma

Nasopharyngeal carcinoma, which is very frequent in southern China, has in previous investigations been found to be associated with a number of risk factors, including a disease susceptibility gene linked to the HLA-region, p53 alleles and deletions of the chromosome 9p21-22 region, which includes the IFNA and p16 loci. We have therefore studied 64 patients (54 males and 10 females) with nasopharyngeal carcinoma and 99 healthy controls from the Guizhou province in southern China with respect to association with the SspI polymorphism at the IFNA17 locus, and the possible interaction between IFNA17 and p53 alleles in the etiology of nasopharyngeal carcinoma. The frequency of the SspI A1 allele was much higher (P < 10(-10)) in Chinese patients and controls than in a previously reported study of Swedes. Among the patients there was a significant increase in the frequencies of the SspI A2 allele (P = 0.011) and SspI 2-2 genotype with an OR (odds ratio) of 2.76, 95% CI = 1.13-6.73 in relation to the SspI 1-1 type. When combinations of SspI and the p53 codon 72 (BstUI) genotypes were studied a highly significant risk figure was found for the SspI 2-2/BstUI 1-1 (pro/pro) combination (OR = 8.2, 95% CI = 2.2-30.0). No other combinations showed significant risk figures. There was no significant interaction between the SspI 2-2 and BstUI 1-1 types indicating that IFN-alpha and p53 genotypes behave as independent risk factors. Since IFN-alpha is located close to the tumor suppressor gene p16, and intronic p53-haplotypes show stronger association with nasopharynx cancer than the codon 72-polymorphism, both associations may be due to linkage disequilibrium with adjacent genes influencing cell-cycle control.