| Summary: | 碩士 === 中山醫學大學 === 毒理學研究所 === 91 === Lung and colorectal cancers have been the leading causes of cancer death in Taiwan, especially in women. Previously studies indicated that smoking is a contributive factor for various cancers, especially for lung cancer since about 90％ lung cancer incidence in western countries occurrence was associated with cigarette smoking. However, the unique epidemiological characteristics of female lung cancer patients in Taiwan, extremely low smoking population but high cancer mortality, have indicated that in addition to cigarette smoking, there may be other environmental factors being involved in lung tumorigenesis in Taiwan. Previous studies indicated that cooked meats and generated cooking oil fumes both contained various heterocyclic amines which had been confirmed to be able to induce lung cancer and colorectal cancer in animal model, therefore, exposure to heterocyclic amines may be associated with lung and colorectal tumorigenesis in Taiwan. CYP1A2 and NAT2 are two major enzymes involved in the metabolism of heterocyclic amines, therefore, 178 lung cancer patients, 102 colorectal cancer patients and 167 non-cancer controls were recruited into this study and subjected to genotype analysis by PCR-RFLP to investigate the relationships between the genetic polymorphism of these two metabolic enzymes and these two heterocyclic amines-related cancers. Compared with slow acetylator genotype, the OR of individuals with NAT2 fast acetylator genotype for lung cancer and colorectal cancer was 3.10 and 1.95, respectively, and was even increased to 4.05 and 7.12 in female populations. Due to lacking smoking-related information of colorectal cancer patients, lung cancer patients were divided into 4 groups, based on gender and smoking status, for further analysis. The results showed that the OR of non-smoking female with NAT2 fast acetylator genotype for lung cancer was as high as 3.48. This result indicated nonsmoking female with NAT2 fast acetylator had a higher lung cancer risk than male in Taiwan. A possible explanation for such higher risk may be that Taiwanese women spent a long cooking time in kitchen and therefore, may be exposed to a higher amount of cooking oil fumes than male. From a further analysis for the interaction of CYP1A2 and NAT2 genotype, it was found that the coexistence of CYP1A2 high or low and NAT2 fast genotype resulted in an even higher risk for lung cancer than just considering NAT2 genotype only, however, such relationship was not found for colorectal cancer. Such difference could be due to different exposure routes and exposure levels. In conclusion, the occurrence of lung cancer and colorectal cancer may be associated with heterocyclic amines exposure, however, the females appear to be more susceptible than male to exposure heterocyclic amines. In addition to the longer time spent on cooking in the kitchen, other environmental factors that may contribute to the higher susceptibility of Taiwanese females to heterocyclic amines exposure need to be further studied.
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