There is an association between HLA phenotype and NPC risk. The association between HLA-A2 and NPC was first reported among Chinese in Singapore {2364}. Subsequent studies have confirmed the association of HLA A2-B46 haplotype with NPC in many different countries {382,1089,1223,1565,1567, 2365,2366}. In addition, increased risk of NPC has been found in individuals harbouring HLA B17 in southern China {1567,2874}, Singapore {382} and Malaysia {381}. Haplotypes A2-B17 {2895}, A2-B38 {1565}, and A2-B16 {2827} are also shown to be associated with increased risk of NPC. These findings are further supported by linkage or association studies that provide evidence for a NPC predisposing gene in close linkage with the HLA locus {1565, 1567,1947}. There is a negative association with NPC risk for alleles A11, B13

Fig. 2.19 Nasopharyngeal carcinoma. Both the carcinoma cells and normal basal cells are immunoreactive for p63.

and B22 {916}. On the other hand, an association between HLA and NPC has not been found in NPC patients in Alaskan Eskimos, Indians {1427}, North Africans {208,1071,1762} and Caucasians {313,314,1769}.

GSTM1 and CYP2E1

Polymorphism of some metabolic enzyme genes has been reported to influence susceptibility to NPC. Glutathione S-transferase M1 (GSTM1) detoxifies benzopyrene and other carcinogens in tobacco smoke. Studies on association between absence of GSTM1 and increased risk for NPC are conflicting {415,1857}.

The cytochrome P450 2E1 (CYP2E1) enzyme catalyzes the metabolic activation of low-molecular weight nitrosamines such as those detected in NPC-associat-ed foods. A variant form of the gene that is detectable by Rsa I digestion (the c2 allele) has been shown to exhibit higher enzymatic activity. If dietary nitrosamines from preserved foods indeed play a direct role in NPC development, exposed individuals possessing different CYP2E1 genotypes may experience differential levels of NPC risk. In a population-based case-control study from Taiwan, individuals possessing the c2/c2 genotype experienced a 2.6-fold risk relative to those with one or two copies of the wild-type allele {1088}. This finding adds to the evidence that nitrosamine-containing preserved foods are important nasopharyn-geal carcinogens.

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