| Abstract: | 惡性腫瘤從1982年以來一直是國人十大死因之首，其中肺癌及大腸癌的死亡率分別高居台灣癌症死亡的第一、三位。過去研究已指出抽菸會導致癌症的發生，其中又以肺癌和抽菸的關係最為密切，在歐美有近九成肺癌的發生與抽菸有關。在台灣抽菸女性人口雖僅占3％左右，但肺癌的死亡率竟高居女性癌症死亡率的第一位，顯示除了抽菸之外，尚有其它的因子參與台灣女性肺癌的形成。有研究指出廚房油煙與台灣女性罹患肺癌有關。過去研究顯示高溫烹調肉類所產生的油煙和肉類食品中含有異環胺類化合物。而這類化合物在動物實驗中，已被證實會引起實驗動物發生肺癌和大腸癌，因此推測異環胺類化合物暴露與台灣肺癌及大腸癌的發生可能有些相關。異環胺類化合物在人體主要是經由 CYP1A2 和NAT2 這兩種酵素進行代謝活化，因此本研究選取178位肺癌患者、102位大腸癌患者分別和167位非癌症患者，利用 PCR-RFLP 的方法分析這兩種代謝酵素基因多形性，並進一步探討這些基因多形性，是否與經由呼吸或飲食這兩種不同暴露形式所引起的癌症有關？結果發現表現型為NAT2 fast acetylator者，罹患肺癌及大腸癌的危險性分別為 slow acetylator 的3.10倍及1.95倍，而在女性族群中更增加為4.05倍及7.12倍。由於本研究未收集到大腸癌患者之抽菸資料，因此只將肺癌研究族群分為不抽菸及抽菸男、女性四組進行分析，結果發現不抽菸女性之NAT2 fast acetylator罹患肺癌的危險性較slow acetylator高3.48倍，其他三組則皆未達統計上之差異，由以上之結果顯示NAT2 fast acetylator與台灣不抽菸女性較抽菸與不抽菸男性罹患肺癌之相關性為高。由於在台灣大多是女性在廚房準備三餐，因此推測暴露油煙的量，可能較男性為高。當分析CYP1A2及NAT2基因型交互作用與罹患肺癌與大腸癌之相關性時發現，CYP1A2 high or low +NAT2 fast基因型較單獨考慮 NAT2 基因型時有較高罹患肺癌的危險性，但在大腸癌病患中則無此現象，推測此差異應與肺及大腸暴露異環胺類的途徑及暴露量不同有關。綜合以上的結果推測，在台灣，罹患肺癌及大腸癌與異環胺類化合物之暴露都有些相關性，然而女性對來自香菸、油煙或食物中異環胺類致癌物的易感性似乎高於男性。除了女性較男性有較高暴露廚房油煙的機會外，是否還有其他環境致癌物需要CYP1A2 與NAT2代謝活化而引起台灣女性罹患肺癌或大腸癌，則需進一步的研究。
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. |
