Investigation of genetic variation in the alcohol metabolism genes and other key

酒精代谢基因等关键遗传变异的研究

• 批准号: 8119585
• 负责人: James Dowling MCKAY
• 金额: $ 8.74万
• 依托单位: INTERNATIONAL AGENCY FOR RES ON CANCER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8119585
• 关键词: Affect; African; Alcohols; Asians; Biocompatible Materials; Case-Control Studies; Chromosomes, Human, Pair 4; Country; DNA; Disease; Environmental Exposure; Ethanol Metabolism; Ethnic Origin; European; Exposure to; Gene Cluster; Genes; Genetic Predisposition to Disease; Genetic Variation; Genotype; Goals; Human Chromosomes; Human Genome; Human Papillomavirus; Individual; International; International Agency for Research on Cancer; Investigation; Malignant Neoplasms; Malignant neoplasm of pharynx; Oral; Oral cavity; Oropharyngeal; Pharyngeal structure; Phase; Play; Population; Predisposition; Principal Investigator; Resources; Risk; Risk Factors; Role; Tobacco; Upper aerodigestive tract cancer; Variant; Work; cancer genome; cancer risk; genetic variant; genome wide association study; malignant mouth neoplasm; programs; public health relevance; repository

DESCRIPTION (provided by applicant): Exposure to tobacco and alcohol are the major risk factors involved in oral cancer susceptibility. Genetic susceptibility plays a role, with variation in the genes involved in metabolism of alcohol, particularly the ADH gene cluster on human chromosome 4, appearing to contribute to disease. The International Agency for Research on Cancer (IARC) has developed a multicentre case-control study (The IARC multicenter oral cancer study) of approximately 1600 cases and 1600 control individuals from 9 different countries and three major ethnicities to investigate oral risk factors, notably exposure to human papillomavirus (HPV), tobacco and alcohol. The goal of the project described in this application is to investigate new findings from a separate large genome wide association study of upper aerodigestive tract cancer in the specific context context of oral cancers. In particular we will investigate 30 genetic variants in the IARC international oral cancer study and investigate how these affect risk in European, Asian and African populations. Public Health Relevance: While exposure to tobacco and alcohol the key risk factors, genetic variation is also thought to play a role in susceptibility to cancers of the oral cavity and pharynx. The goal of this project is to investigate new findings from a separate genome wide association study of upper-areodigestive tract cancer in the specific context of cancers of the oral cavity and pharynx.

描述（由申请人提供）：接触烟草和酒精是口腔癌易感性的主要危险因素。遗传易感性发挥着重要作用，涉及酒精代谢的基因的变异，尤其是人类 4 号染色体上的 ADH 基因簇，似乎与疾病有关。国际癌症研究机构 (IARC) 开展了一项多中心病例对照研究（IARC 多中心口腔癌研究），涉及来自 9 个不同国家和三个主要种族的约 1600 例病例和 1600 名对照个体，以调查口腔风险因素，特别是暴露人类乳头瘤病毒 (HPV)、烟草和酒精。本申请中描述的项目的目标是调查口腔癌特定背景下上呼吸消化道癌的独立大型基因组范围关联研究的新发现。特别是，我们将调查 IARC 国际口腔癌研究中的 30 种遗传变异，并研究它们如何影响欧洲、亚洲和非洲人群的风险。 公共健康相关性：虽然接触烟草和酒精是主要危险因素，但遗传变异也被认为在口腔和咽部癌症的易感性中发挥着作用。该项目的目标是在口腔和咽部癌症的特定背景下调查上消化道癌症的独立全基因组关联研究的新发现。

项目成果

Genetic variants in nicotine addiction and alcohol metabolism genes, oral cancer risk and the propensity to smoke and drink alcohol: a replication study in India.

• DOI: 10.1371/journal.pone.0088240
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Anantharaman D;Chabrier A;Gaborieau V;Franceschi S;Herrero R;Rajkumar T;Samant T;Mahimkar MB;Brennan P;McKay JD
• 通讯作者: McKay JD