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標題: 探討乳癌病患身體質量指數及雌性激素代謝活化基因之多型性與白血球去鹼基核酸背景值之相關性
Investigation of the association of body mass index and polymorphisms of genes responsible for estrogen bioactivation with the background levels of abasic sites in white blood cells derived from breast cancer patients
作者: 劉致辰
Liu, Chin-Chen
關鍵字: breast cancer
abasic site
single nucleotide polymorphism
出版社: 環境工程學系所
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摘要: 乳癌是台灣女性最普遍癌症之一,在許多流行病學研究指出雌性激素劑量累積為乳癌風險之重要因素。實驗室先前研究證實雌性激素醌類代謝物會直接造成DNA (deoxyribonucleic acid) 氧化損害而形成去鹼基核酸 (AP sites),此即為雌性激素致癌的重要起始化作用 (initiation)。本研究主要目的為探討台灣女性乳癌病患之乳癌風險因子,包括年齡、身體質量指數 (BMI) 及雌性激素代謝基因之基因多型性與去鹼基核酸背景值之相關性,此研究將以102位台灣女性乳癌病患之白血球進行分析。 研究結果顯示,乳癌病患AP sites背景值為 94.3 ± 107/106核苷酸 (平均 ± 標準偏差)。而乳癌病患之雌性激素代謝活化之對偶基因變異 (variant alleles) 頻率CYP1A1 T3801C與CYP1B1 Leu432Val分別為39.7%與7.35%。我們也發現在BMI < 27之乳癌病患其AP sites背景值較BMI ≧ 27病患為高,而此趨勢在年齡小於50歲研究族群更明顯。此外,乳癌病患CYP1A1 T3801C 不同基因型病患其AP sites背景值約略相當;但在年齡小於50歲的乳癌病患中,CYP1B1 Leu432Val Leu/Val+Val/Val基因型 (高活性) 之AP sites背景值較Leu/Leu基因型高約1.4倍。由AP site cleavage assay結果指出,乳癌病患之AP sites可能是由氧化作用引起。 綜合上述研究結果可發現,乳癌風險因子包括年齡及BMI與乳癌病患之AP sites背景值呈負相關;而CYP1B1 Leu432Val對偶基因之變異型與乳癌病患AP sites背景值呈正相關。
Breast cancer is one of the most prevalent cancer among women in Taiwan. Epidemiological studies suggest that cumulative estrogen dose is a key determinant of breast cancer risks. Laboratory research provides evidence that estrogen quinone-derived direct and oxidative DNA (deoxyribonucleic acid) damage and the subsequent formation of abasic sites (AP sites) play an important role in the initiation of estrogen carcinogenesis. The objective of this research was to investigate association of the risk factors of breast cancer, including age, body mass index (BMI), and polymorphism of genes responsible for estrogen disposition, with the background levels of AP sites in white blood cells derived from 102 female breast cancer patients in Taiwan. Results indicated that the background levels of AP sites (mean ± SD) in breast cancer patients was 94.3 ± 107 per 106 nucleotides. The frequencies of variant alleles of CYP1A1 T3801C and CYP1B1 Leu432Val were estimated to be 39.7% and 7.35%, respectively. We noticed that the background levels of AP sites in breast cancer patients with BMI < 27 were greater than those with BMI ≧ 27, and the tendency was more obvious in subjects under 50 years of age. Relatively similar levels of AP sites were detected in subjects with SNP of CYP1A1 T3801C T/T genotype when compared to those with T/C and C/C genotype. A 1.4-fold increase in the number of AP sites was detected in patients (age < 50) with CYP1B1 Leu432Val Leu/Val+Val/Val genotype (high-activity) when compared to those with Leu/Leu genotype. Additionally, results from the AP site cleavage assay indicated that the AP sites detected in breast cancer patients were likely to derive from oxidative events. The background levels of AP sites had no significant difference distinguished by age or BMI in breast cancer patients who received chemotherapy. In conclusions, the risk factors of developing breast cancer, including age, BMI, and variant allele of CYP1A1 T3801C, were negatively correlated with the background levels of AP sites whereas variant allele of CYP1B1 Leu432Val were positively correlated with the background levels of AP sites in breast cancer patients.
其他識別: U0005-1908201114473200
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