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1 Research and 2Pathology Division, National Cancer Institute, Bangkok 10400, Thailand.
3 Unit of Human Biology and Genetics, Department of Biological Sciences, School of Science, University of Tokyo, Tokyo, Japan.

      Nasopharyngeal carcinoma (NPC) remains a serious health problem in southern China and Southeast Asian countries. Genetic susceptibility is an important factor for cancer development. Polymorphism of genes that encode enzymes involved in metabolic activation and detoxification of xenobiotics has been reported to be associated with susceptibility of NPC. To determine association between cytochrome P450 2A6 (CYP2A6 ) and glutathione S-transferase M1 gene (GSTM1 ) polymorphism and NPC risk in Thais, 78 NPC patients and 145 age-matched healthy controls were examined for CYP2A6  deletion genotype (*4C/*4C ) and GSTM1  null genotype (GSTM1- ) by using PCR-RFLP and PCR assays, respectively. Overall, no association was found between CYP2A6*4C/*4C  and NPC risk. Interestingly, carriers of at least one *4C  allele or (*1A/*4C  + *1B/*4C  + *4C/*4C ) genotype had a 3-fold increased risk for NPC (95% CI, 1.1-8.4) and males had a 11-fold higher risk for NPC than females. In addition, carriers of at least one *4C  allele had a 5-fold and 9-fold higher risk for NPC of WHO type I than WHO types II and III. Further, the carriers of at least one *4C  allele had a 9-fold higher risk for NPC stage I and II than stage III and IV. When subjects were categorized into 3 groups of age >40, >45 and >50 years, it was found that risk for NPC tended to increase with age for carriers of at least one *4C  allele. For GSTM1  polymorphism, no statistically significant differences were observed in the frequency of GSTM1 - between cases and controls. Among NPC patients, a significant association existed between GSTM1 - and NPC WHO type III (P <0.05) with odds ratio (OR) = 2.6 (95% CI = 1.2-6.8), but there was no association with WHO types I and II. When cases and controls were categorized into 3 age groups (>40, >45 and >50 years), the frequencies of GSTM1 - in groups >45 and >50 years were significantly different from those of controls (P<0.05). GSTM1 - carriers over 45 years had a 2-3-fold higher risk for NPC and the risk increased with age (i.e., OR increased from 2.2 to 3.0 for age groups >45 and >50 years). Carriers of combinations of two-risk genotypes (with at least one of *4C  allele or GSTM1- ) had a higher risk for NPC compared with those of one-risk genotype. Based on this study, we suggest that CYP2A6  and GSTM1  polymorphism may play a key role in NPC development and may be a useful tool for early detection and monitoring of NPC in Thailand.

ที่มา ABSTRACT นำเสนอที่ การประชุมวิชาการสมาคมพิษวิทยาแห่งประเทศไทย ประจำปี 2547 อาหารกับความปลอดภัย วันศุกร์ที่ 17 ธันวาคม 2547 โรงแรมมิราเคิลแกรนด์ กรุงเทพฯ