International Head and Neck Cancer Consortium

描述(由申请人提供)： 在全球范围内，2000年估计有50万头颈癌病例和30万人死于头颈癌。据报道，在美国和欧洲，年轻人的发病率不断上升，尤其是舌癌。虽然烟草和酒精至少占头颈部癌症的75%是众所周知的，但重要的病因学问题仍有待解决：(I)低外显性遗传易感因素(例如SNPs)的作用及其与环境因素的相互作用；(Ii)罕见亚群的病因学，包括发病年龄较小的人群、不吸烟和不饮酒的人；(Iii)人类乳头瘤病毒(HPV)的影响，特别是与癌症亚群的关系。需要新的方法来克服以前对这些问题的研究的局限性，特别是样本容量的限制。我们最近成立了国际头颈癌流行病学联合会(INHANCE)，作为一种这样的方法，最初是基于领导头颈部癌症大分子流行病学研究的10个研究小组的合作。该联盟目前提供了9000对病例对照的问卷资料和生物样本。在2006年完成所有研究后，将有14,000对病例对照；如果纳入更多的研究，这一数字可能会进一步增加。作为该联盟的第一步，我们将对以下两组进行汇总分析：(I)年轻受试者，(Ii)不吸烟和不饮酒者。我们的具体目标是：1)对于年轻发病的头颈部癌症，测试烟草和酒精习惯的较小作用的假设，以及癌症家族史、大麻使用、无烟烟草和性史的较强作用的假设；2)确定烟草与不饮酒者、酒精与非吸烟者的关系，以及大麻使用、被动吸烟和低体重指数对头颈部癌症的病因作用；3)从所有研究、调查问卷和正在进行基因分型的SNP列表中获得，以评估不同研究之间的数据可比性，以便进一步联合应用。该联盟未来的方向将是协调优先SNPs列表中的基因分型，并评估HPV感染的影响。我们预计，INHANCE联盟将是朝着提高我们对头颈部癌症的原因和机制的理解迈出的重要一步，也是长期合作的开始。

DESCRIPTION (provided by applicant): Worldwide, an estimated half a million head & neck cancer cases and 300,000 deaths due to head & neck cancer occurred in the year 2000. Increasing incidence among young individuals, especially for tongue carcinomas, has been reported in the US and Europe. While it is well-established that tobacco and alcohol account for at least 75% of head & neck cancers, important etiologic questions remain to be addressed: (i) the role of low penetrance genetic susceptibility factors (e.g. SNPs) and their interactions with environmental factors, (ii) etiology in rare subgroups including young age at onset, and nonsmokers and nondrinkers, (iii) the effect of human papillomavirus (HPV), particularly with respect to cancer subsite. Novel approaches are necessary to overcome the limitations in previous studies of these issues, and in particular the constrained sample sizes. We recently established the international Head and Neck Cancer Epidemiology (INHANCE) Consortium as one such approach, based initially on the collaboration of 10 research groups leading large molecular epidemiology studies of head & neck cancer. The consortium provides questionnaire information and biological samples from 9,000 case-control pairs at present. Upon completion of all studies in 2006, there will be 14,000 case-control pairs; which may further increase with the inclusion of additional studies. As a first step for the consortium, we will conduct two sets of pooled analyses on: (i) young subjects, (ii) nonsmokers and nondrinkers. Our specific aims are: 1) for young onset head & neck cancers, to test the hypotheses of a lesser role of tobacco and alcohol habits, and a stronger role for family history of cancer, marijuana use, smokeless tobacco, and sexual history, 2) to identify the relationship of tobacco in nondrinkers, of alcohol in nonsmokers, and the etiologic roles of marijuana use, passive smoking and low body mass index independent from those of tobacco and alcohol for head & neck cancer, 3) to obtain from all studies, questionnaires and lists of SNPs being genotyped to evaluate data comparability across studies for further joint applications. Future directions for the consortium will be to coordinate genotyping from a list of priority SNPs and to assess the effect of HPV infection. We anticipate that the INHANCE consortium will be a major step toward improving our understanding of the causes and mechanisms of head & neck cancers and the beginning of a long-standing cooperation.