南台灣地區乳癌患者之化療藥物相關基因型分布與復發關聯性之分析

The prevalence of chemo-agents related polymorphisms in southern Taiwanese breast cancer patients and the correlation of recurrence status

王怡惠(Yi-Hui Wang)

指導教授 ： 林綉茹

共同指導教授 ： 侯明鋒(Ming-Feng Hou)

高雄醫學大學/醫學院/醫學研究所/碩士(2007年)

https://doi.org/10.6832/KMU.2007.00095

摘要

為有效提升乳癌患者臨床上使用化學治療藥物之療效，本計畫希望藉由人類基因序列解碼之後，所引導出之單核苷酸多型性 (single nucleotide polymorphism, SNP)的概念，加上合併藥物基因體學 (Pharmocogenomics)的理論基礎，深入探討與化療藥物作用相關之基因型，是否具有足以影響藥效及可否提供臨床用藥前療效評估之能力。本研究初步分析來自高雄醫學大學附設中和紀念醫院及成大醫院之192位台灣南部乳癌患者化療藥物相關基因多型性分布以及各種族間的差異，並與臨床復發與否之結果做初步分析，希望能作為臨床上乳癌患者療效反應相關性研究的基礎。本實驗所選取之乳癌患者所採取的合併化療藥物為FEC (5-Flurouracil + Epirubicin + Cyclophosphamide)，而此研究中所選取與FEC藥物相關之基因多型性如下：5,10-methylenetetrahydrofolate reductase C677T (MTHFR C677T)、thymidylate synthetase double or triple tandem repeat (TS 3R or 2R)、multidrug resistance 1 C3435T (MDR1 C3435T)、glutathione S-transferase pi A313G (GSTP1 A313G)。實驗結果發現，當合併MDR1 3435CC、MTHFR 677CC二個易感性基因型 (RR:3.12, 95%CI: 1.24-7.82, P=0.015)同時評估或合併MDR1 3435CC、GSTP1 313AA以及MTHFR 677CC這三個易感性基因型 (RR:3.17, 95%CI: 1.10-9.11, p=0.033)同時評估，可以用來預測乳癌患者接受FEC化療預後的參考。本研究之各個基因型分布如下：MTHFR 677CC 57.3%、MTHFR 677CT 35.4%、MTHFR 677TT 7.3%；GSTP1 313AA 62.5%、GSTP1 313AG 34.4%、GSTP1 313GG 3.1%；MDR1 3435CC 40.6%、MDR1 3435CT 44.8%、MDR1 3435TT 14.6%；TS 3R3R 66.1%、TS 2R3R 31.8%、TS 2R2R 2.1%。此研究可提供南台灣地區乳癌患者化療相關基因型之分子流行病學探討，更可提供臨床上乳癌患者FEC化療預後評估之基礎。

關鍵字

乳癌 ； 化療 ； 單核苷酸多型性 ； 藥物基因體學 ； 復發

並列摘要

In order to elevate the chemotherapeutic response of breast cancer patients, the project hope to use the conception of single nucleotide polymorphism, and combine the basic theory of pharmocogenomics, to deeply investigate chemotherapeutic reagent related genotypes, whether having ability to affect the therapy or afford the valuation before chemotherapy. In our research, first, we gather 192 Taiwanese breast cancer patients from Chung-Ho Memorial Hospital, Kaohsiung Medical University and National Cheng Kung University Hospital, analyze the distributions of chemotherapeutic reagents related genotypes and the differences between races, furthermore, analyze the relationship between genotypes and clinical recurrence status, hoping be a basis of relevant studies. In our research, the combined chemotherapy drug used in the breast cancer patients is FEC (5-Flurouracil + Epirubicin + Cyclophosphamide) and related polymorphisms were as follows: 5,10-methylenetetrahydrofolate reductase C677T (MTHFR C677T)、thymidylate synthetase double or triple tandem repeat (TS 3R or 2R)、multidrug resistance 1 C3435T (MDR1 C3435T)、glutathione S-transferase pi A313G (GSTP1 A313G). We found that when combine two sencitive genotypes MDR1 3435CC and MTHFR 677CC (RR:3.12, 95%CI: 1.24-7.82, P=0.015), or combine three susceptibility genotypes MDR1 3435CC, GSTP1 313AA and MTHFR 677CC (RR:3.17, 95%CI:1.10-9.11, p=0.033), to estimate simultaneously, could predict the prognosis of breast cancer patients who treated with FEC. The genotype frequency of our research were as follow: MTHFR 677CC 57.3%、MTHFR 677CT 35.4%、MTHFR 677TT 7.3%；GSTP1 313AA 62.5%、GSTP1 313AG 34.4%、GSTP1 313GG 3.1%；MDR1 3435CC 40.6%、MDR1 3435CT 44.8%、MDR1 3435TT 14.6%；TS 3R3R 66.1%、TS 2R3R 31.8%、TS 2R2R 2.1%. The research could afford the molecular epidemiology of chemotherapeutic agent related genotypes in Taiwanese breast cancer patients, also could provide the assessment of prognosis of breast cancer patients received FEC chemotherapy.

並列關鍵字

breast cancer ； pharmocogenomics ； single nucleotide polymorphism ； chemotherapy ； recurrence

參考文獻

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