氧化酵素基因多型性與乳癌預後之研究

Polymorphisms in genes related to oxidative stress and prognosis for breast cancer

梁景淵(Jin-Yuan Liang)

指導教授 ： 蔡麗玉

高雄醫學大學/健康科學院/醫學檢驗生物技術學研究所/碩士(2012年)

摘要

目的：因為粒線體的MnSOD會將超氧陰離子自由基轉化成H2O2，接著CAT或GPx1會將H2O2變成水，或者由MPO將H2O2轉變成次氯酸。我們推測基因的變異將影響乳癌的預後，改變病人的存活表現。
方法：將162位乳癌病人的DNA做氧化壓力酵素的基因分型(MnSOD -9T>C, CAT -262C>T, MPO -463G>A and GPx1 Pro198Leu)，用Cox迴歸分析氧化壓力酵素的基因型與無癌症復發存活率的關係。
結果：同時帶有CAT TC型與MnSOD TT型的病人，會增加4.4倍的死亡風險(hazard ratio, 4.40; 95% confidence interval, 1.85-10.49; P = 0.001)，CAT基因與MPO或GPx1基因合併分析也有明顯增加死亡風險。
結論：帶有CAT基因與其他基因的變異，在合併分析下，確實發現會影響乳癌的治療預後。

關鍵字

氧化酵素基因 ； 乳癌預後

並列摘要

Purpose: Because mitochondrial manganese superoxide dismutase (MnSOD) converts of superoxide radicals to H2O2, which is neutralized sequentially into H2O by catalase (CAT) or glutathione peroxidase 1 (GPx1) and converted H2O2 to highly reactive hypochlorous acid by myeloperoxidase (MPO), we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival.
Methods: Genotypes of oxidative stress-related enzymes (MnSOD -9T>C, CAT -262C>T, MPO -463G>A and GPx1 Pro198Leu) were analyzed in 162 female patients with breast cancer, and Cox proportional hazards models were used to calculate disease-free survival (DFS) associated with Genotypes of oxidative stress-related enzymes.
Result: Women with CAT TC and MnSOD TT had a 4.4-fold increase in hazard of death (hazard ratio, 4.40; 95% confidence interval, 1.85-10.49; P = 0.001). Combining genotype for CAT and MPO as well as CAT and GPx1 also significantly increased the hazard of death.
Conclusion: These results indicate that gene variants of combining genotypes for CAT and all the others that impact oxidative stress modify prognosis after treatment for breast cancer.

並列關鍵字

Polymorphisms in genes related to oxidative stress ； prognosis for breast cancer

參考文獻

[1] King-Jen Chang, Wen-Hung Kuo, Ming-Yang Wang: The Epidemiology of Breast Cancer in Taiwan. K. J. Chang et al./JCOS 24(2008) 85-93

[2] 乳癌診斷與治療共識. 國家衛生研究院2004.

[3] 乳癌治療的新趨勢. 腫瘤護理雜誌 第九卷增訂刊2009

[4] Hou, M., Chen, F., & Ou-Yang, F. (2008). Changing Trend in Breast Cancer Surgery. Journal of Chinese Oncology Society, 24(2), 6.

[5] Nielsen, H. M., Overgaard, M., Grau, C., Jensen, A. R., & Overgaard, J. (2006). Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: Long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies. Journal of Clinical Oncologyl, 24(15), 2268-2275.