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

描述(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。遗传易感性起到了一定作用，涉及酒精新陈代谢的基因变异，特别是人类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多中心口腔癌症研究)，对象是来自9个不同国家和三个主要民族的约1600名病例和1600名对照个人，以调查口腔危险因素，特别是接触人乳头瘤病毒(HPV)、烟草和酒精。本申请中描述的项目的目标是在口腔癌的特定背景下，从一个单独的大基因组范围的上消化道癌症关联研究中调查新的发现。特别是，我们将调查IARC国际口腔癌症研究中的30个基因变异，并调查这些变异如何影响欧洲、亚洲和非洲人口的风险。 公共卫生相关性：虽然接触烟草和酒精是关键的危险因素，但基因变异也被认为在口腔和咽部癌症的易感性中起到了作用。这个项目的目标是在口腔和咽部癌症的特定背景下，从一个单独的全基因组相关性研究中调查上消化道癌症的新发现。

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.