Epidemiological and molecular genetic study for environmental and occupational cancers.

环境和职业癌症的流行病学和分子遗传学研究。

• 批准号: 06454235
• 负责人: HARADA Shoji
• 金额: $ 3.78万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454235/
• 关键词: GSTM1 gene deletion; CYP1A1; polymorphism; lung cancer; genetic association; case control study; genetic risk factor; Xenobiotics; genetic risk factor

Individual susceptibility to lung cancer due to occupational and environmental exposures to carcinogenetic agents has been shown to be modulated by host-specific factors with genetic background. Recent studies have suggested that inherited differences in metabolic capacity may play a primary role in susceptibility to environmentally induced cancers. In this respect, polymorphic alleles of Glutathione S-Transferase (GSTM1) which is important in the detoxification of several carcinogens, and of Cytochrome P450 1A1 (CYP1A1) which is biotransforming enzymes, were analyzed in the context of the relationship between controls and lung cancer. Blood samples of the 104 controls and 172 patients were collected from peoples living in Sheng-Yan district of People's Republic of China.PCR and related techniques were used for detection of these polymorphic loci.1) The frequencies of GSTM1 gene deletion was significantly higher in the patients with lung cancer than in controls (P<0.05). In addition, s … More mall cell carcinoma showed the highest association with GSTM1 gene deletion compared with other types of lung cancers such as squamous cell carcinoma and adenocarcinoma.2) The risk of lung cancer is dependent on the extent of the tobacco smoke exposure. This was supposed by our study showing progressive increase in the proportion of the GSTM1 gene deletion in relation to smoking index, in both squamous (P<0.05) and small cell carcinoma groups (P<0.01).3) The different frequencies of GSTM1 gene deletion was observed between the patients under 50 years (85.3%) and over 50 years old (61.8%), which are significantly different (P<0.05). Such observation may be associated with onset of lung cancer. Further study will be necessary to confirm association with onset with onset of lung cancer.4) Several studies have shown that CYP1A1^<**>2 gene is associated with an increased risk of cigarette smoke-induced lung cancer. However, the difference of frequency between the patients with lung cancer and the controls was not significant in our samples. Less

由于职业和环境暴露于致癌物质，个体对肺癌的易感性已被证明是由具有遗传背景的宿主特异性因素调节的。最近的研究表明，代谢能力的遗传差异可能在环境诱发癌症的易感性中起主要作用。在这方面，多态性等位基因的谷胱甘肽S-转移酶（GSTM 1），这是重要的几种致癌物质的解毒，和细胞色素P450 1A 1（CYP 1A 1），这是生物转化酶，进行了分析的背景下，控制和肺癌之间的关系。采用聚合酶链反应（PCR）及相关技术对中华人民共和国沈阳市沈阳地区104名正常人和172名肺癌患者的外周血标本进行多态性检测。结果：1）肺癌患者GSTM 1基因缺失频率显著高于正常人（P<0.05）;此外，S ...更多信息 与其他类型的肺癌如鳞状细胞癌和腺癌相比，小细胞癌与GSTM 1基因缺失的相关性最高。2）肺癌的风险取决于烟草烟雾暴露的程度。我们的研究表明，在吸烟指数相关的GSTM 1基因缺失的比例逐渐增加，在两个鳞状细胞癌中，（P<0.05）和小细胞癌组3）50岁以下患者GSTM 1基因缺失频率不同（P<0.01 50岁以上者占61.8%，差异有统计学意义（P<0.05）。这种观察结果可能与肺癌的发病有关。4）多项研究表明，CYP 1A 1 ^**>2基因与吸烟诱发肺癌的风险增加有关。但在我们的样本中，肺癌患者和对照组之间的频率差异不显著。少

项目成果

S. Homma, et al.: "Site-specific distribution of copper, slenium, and zinc in human kidney by synchrotron radiation induced X-ray fluorescence." Nuclear Instrument and Methods in Physics Research B. 103. 229-232 (1995)

S. Homma 等人：“通过同步加速器辐射诱导的 X 射线荧光，铜、硒和锌在人肾中的位点特异性分布。”

Harada, S.: "Investigation of the genetic markers associated with alcohol liver diseases" Alcohol and Alcoholism. vol 25. 241-246 (1995)

Harada, S.：“与酒精性肝病相关的遗传标记的调查”酒精和酒精中毒。

M. Sagai, et al.: "Diesel exhaust particles (DEP) can cause asthmatic symtoms.Frontiers of Reactive Oxygen Species in Biology and Medicine. (Ed. K. Akasaka)" Excerpta Medica, 4 (1994)

M. Sagai 等人：“柴油机尾气颗粒 (DEP) 可引起哮喘症状。生物学和医学中活性氧的前沿。（Ed. K. Akasaka）” Excerpta Medica，4 (1994)

Harada, S., Nakamura, T., Misawa, S.: "Polymorphism of pentanucleotide repeats in the 5' flanking region of glutathione S-transferase (GST) pi gene." Hum Genet. 93. 223-224 (1994)

Harada, S.、Nakamura, T.、Misawa, S.：“谷胱甘肽 S-转移酶 (GST) pi 基因 5 侧翼区域五核苷酸重复的多态性。”

嵯峨井 勝, 他: "ディーゼル排気微粒子(DEP)による肺がん発生と活性酸素の役割" 日本変異原学会誌. 16. 275-285 (1995)

Masaru Sagai 等人：“柴油机废气颗粒 (DEP) 引起的肺癌发展和活性氧的作用”，日本诱变学会杂志 16. 275-285 (1995)。