アルコール代謝ならびに葉酸代謝酵素の遺伝的多型と大腸がんに関する疫学的研究

酒精代谢和叶酸代谢酶基因多态性与结直肠癌的流行病学研究

• 批准号: 10670333
• 负责人: MURATA Motoi
• 金额: $ 0.7万
• 依托单位: Chiba Cancer Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670333/
• 关键词: Colorectal cancer; Folic acid; MTHFR; Alcohol

We hae already reported that heavy alcohol drinking is associated with coloectal cancer, and also that the alcohol drinkers with the heteroqygous genotype of aldehyde dehydrogenase 2 gene are in a higher risk than other groups. It was speculated that the alcohol-colorectal cancer relationship might be mediated through folate deprivation. On the other hand, Chen et al. (1996) proposed a hypothesis that a genotype difference in a methylene-tetrahydrofolate reductase (MTHFR) gene is also associated with colorectal cancer. Its C to T substitution at nucleoptide 677 introduced a genetic polymorphism with ala(A) and val(V). It was proposed that the V/V homozygotes tend to be less folate deprived so that they are at a low risk of colorectal cancer.This study aimed to ascertain their hypothesis by conducting a case control study. Cases were 179 colon and 113 rectum cancer patients who were surgically streated in Chiba Cancer Center Hospital, and controls were 161 patients of various non-malignant diseases. The genotypes were tested with PCR method applied on peripheral lymphocyte DNA and informations on their life styles were obtained by a self-administerred questionnaire.In the whole male subjects, including cases and controls, frequency of V/V was reduced age-dependently from 19% in 40's to 10% in 70's, and was also disagreed by alcohol drinking habit with 17% in drinkers and 9% in non-drinkers. However, no difference was observed between the cases and controls after adjusting for genders, ages and the drinking habits. We could not find any confirming evidence for the positive association of MTHFR and colorectal cancer.

我们已经报道了大量饮酒与结肠直肠癌有关，而且乙醛脱氢酶2基因杂合型饮酒者比其他人群有更高的风险。据推测，酒精与结直肠癌的关系可能是通过叶酸剥夺介导的。另一方面，Chen等（1996）提出了亚甲基四氢叶酸还原酶（MTHFR）基因的基因型差异也与结直肠癌相关的假说。它的第677位核苷酸由C变为T，导致了ala（A）和瓦尔（V）的遗传多态性。有研究认为V/V纯合子叶酸缺乏程度较低，因此其患大肠癌的风险较低，本研究旨在通过病例对照研究证实这一假说。研究对象为在千叶肿瘤中心医院接受手术治疗的结肠癌患者179例和直肠癌患者113例，对照组为各种非恶性疾病患者161例。用外周血淋巴细胞DNA聚合酶链反应（PCR）方法检测基因型，并自行调查生活方式，结果表明：在所有男性受试者中，V/V频率随年龄的增长而降低，从40年代的19%下降到70年代的10%，饮酒者的V/V频率为17%，不饮酒者为9%。然而，在调整性别、年龄和饮酒习惯后，病例组和对照组之间没有观察到差异。我们无法找到任何证实MTHFR与结直肠癌正相关的证据。

项目成果

Masatoshi Takgawa, Motoi Murata et al.: "Prognostic value of mutations and a germ line polymorphism of the p53 gene in non-small cell lung carcinoma : association with clinicopathological features"Cancer Letters. 128. 93-99 (1998)

Masatoshi Takkawa、Motoi Murata 等人：“非小细胞肺癌中 p53 基因突变和种系多态性的预后价值：与临床病理特征的关联”Cancer Letters。

Motoi Murata, Masatoshi Tagawa et al.: "Genptype difference of aldehyde dehydrogenase 2 gene in alcohol drinkersinfluences the incidence of Japanese colorectal cancer patients"Jpn. J. Cancer Res.. 90. 711-719 (1999)

Motoi Murata、Masatoshi Takawa等：“饮酒者乙醛脱氢酶2基因的基因型差异影响日本结直肠癌患者的发病率”Jpn.

Masatoshi Tagawa, Motoi Murata et al.: "Prognostic value of mutations and a germ line polymorphism of the p53 gene in non-small cell lung carcinoma: association with clinicopathological features."Cancer Letters. 128. 93-99 (1998)

Masatoshi Takawa、Motoi Murata 等人：“非小细胞肺癌中 p53 基因突变和种系多态性的预后价值：与临床病理学特征的关联。”Cancer Letters。

Masatoshi Tagawa,Motoi Murata et al.: "Prognostic value of mutations and a germ line polymorphism of the p53 gene in non-small cell lung carcinoma: association with clinicopathological features." Cancer Letters. 128. 93-99 (1998)

Masatoshi Takawa、Motoi Murata 等人：“p53 基因突变和种系多态性在非小细胞肺癌中的预后价值：与临床病理特征的关联。”

Motoi Murata, Masatoshi Tagawa et al.: "Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients"Jpn. J. Cancer Res.. 90. 711-719 (1999)

Motoi Murata、Masatoshi Takawa等：“饮酒者乙醛脱氢酶2基因的基因型差异影响日本结直肠癌患者的发病率”Jpn.