2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38379According to the report from Department of Health, cervical cancer (49.8 per 100,000 females) was the most prevalent malignancy in Taiwanese women. It was also the fifth leading cause of cancer deaths among women (8.3 per 100,000 females). Many epidemiologic researchers have found that high-risk HPV (human papillomavirus) infection, active cigarette smoking, passive smoking, reproductive condition, and sexual behavior were the major risk factors of cervical cancer. However, those factors can’t fully explain the entire pathogenesis of cervical cancer. Some individuals under the exposure to those risk factors didn’t develop cervical intraepithelial neoplasm (CIN), suggesting genetic components may play another pivotal role in cervical carcinogenesis. The CYP1A1 gene encoding aryl hydrocarbon hydroxylase (AHH) enzyme metabolizes polycyclic aromatic hydrocarbons (PAHs), which are the major constituent from active or passive smoking. Many studies have shown that phase I enzymes, such as P4501A1, metabolize organic compounds into reactive compounds which can damage cells and DNA. Moreover, GSTM1 (m), GSTT1 (q), and GSTP1 (p) have been suggested as detoxifying genes because of their ability to regulate the conjugation of a wide range of xenobiotics, including environmental carcinogens, in order to excrete as hydrophilic metabolites. Individuals with different abilities to metabolize and detoxify carcinogens show different risks to develop cancer. Although a few studies investigated the association between metabolize enzyme gene polymorphism, phase I cytochrome P450s or phase II GST, and the progression of cervical neoplasm, the results are still controversial. In addition, all studies did not investigate the relationship between genotypes and phenotypes of those candidate metabolizing genetic polymorphisms. Therefore, in the 2-year research project, we will complete three specific aims: (1) To conduct a community-based case–control study to investigate the role of genetic susceptibility in the development of cervical neoplasm. Under this particular aim, we will focus on metabolizing genetic polymorphisms, including phase I cytochrome P450s, P4501A1, and phase II GST, GSTM1, GSTT1, and GSTP1; (2)To investigate gene-to-gene and gene-to-environment relationships in high-risk HPV infection, active smoking, or second-hand smoking that is associated with cervical neoplasm risk.; (3) To estimate gene expression level among different gene polymorphism individuals. With cervical cancer being the great impact on Taiwanese women, this study is of great significance to public health, because we will be able to delineate a subpopulation more susceptible to cervical neoplasm here and the interaction between susceptible gene polymorphism and environmental risk factors on cervical neoplasm. We firmly believe that we can achieve our research goals because we have the cooperation and collaboration of Kaohsiung County Health Bureau personnel and have established a laboratory capable of analyzing genetic polymorphisms and gene expression level.衛生署資料顯示，子宮頸癌為臺灣婦女癌症發生率的第一位，約每十萬位婦女，就 有49.8 位罹患子宮頸癌。許多流行病學研究發現，高危險性人類乳突狀病毒感染、抽 煙、暴露二手煙等，是導致婦女罹患子宮頸癌的重要因素。但是，有些個體雖暴露於以 上的危險因素之中，但並未罹患子宮頸癌。因此，個人的基因型態在決定其是否罹患子 宮頸癌上扮演重要角色。Aryl hydrocarbon hydroxylase (AHH)酵素中CYP1A1 的基因 與抽煙或二手煙中所含的致癌物質，例如PAH 的代謝有關。研究發現，phase I 酵素， 例如P4501A1 在代謝轉換過程中，可能會對細胞及DNA 造成傷害。有研究指出phase II 酵素，例如GSTM1、GSTT1、及GSTP1 可將致癌物質轉換為親水性代謝物以排出體外。 因此個體代謝致癌物質及去毒化的能力，可能會影響其是否會罹患癌症。雖然有研究曾 探討代謝性酵素，例如phase I cytochrome P450s 或phase II GST 酵素的基因多型性 與罹患子宮頸癌的相關性。但是這些研究，並無一致性結果。此外，研究中並沒有探討 個體的基因多型性是否會改變其基因的表現。本研究將以二年的時間進行一個以社區為 基礎的個案對照研究以探討: (一)、phase I 酵素，例如P4501A1 及phase II 酵素，例如GSTM1 、GSTT1 、及GSTP1 基因多型性與子宮頸癌的相關性。 (二) 、基因與基因，及基因與環境中危險因子，與子宮頸癌的相關性。 (三) 、個體基因多型性是否會改變其基因的表現。 子宮頸癌是婦女癌症死亡率的第五位。本研究對公共衛生而言具有顯著的貢獻，此研究 結果可得知與子宮頸癌有關的基因型，及基因與基因或基因與環境中危險因子的相互作 用下，是否會增加或減少婦女罹患子宮頸癌的危險性。本研究已獲得高雄縣衛生局人員 同意協助與合作，加上本研究室已具有此方面的經驗與技能，我們確信，在經費的支持 下必能如期完成此計畫。Project