Clefts/Craniofacial Anomalies and Cancer Susceptibility

当前提案寻求激活K99 R 00合同（1 K99/R 00-DE 018413）的ROO阶段。的PI 已经完成了他的K99主要目标：了解口裂的病因学、流行病学和表型 并获得统计遗传学方面的专业知识。此外，职业发展是主要目标之一 在K99阶段探索，重点是负责任的研究行为，科学管理 领导力和道德。 匹兹堡大学的环境和牙科医学院的基础设施已经 作为一名独立的科学家，PI的进步至关重要。颅面出生缺陷是最常见的 一种新生儿先天性畸形。口腔裂的病因是复杂的，有多种遗传和 环境影响。文献中提出，癌症和先天畸形 有时可能有共同的病因。该项目的目的是确定基因，可以有助于 颅面畸形和癌症，并有助于更好地了解复杂的颅面 和牙齿遗传疾病。 主要研究者根据计划的时间框架妥善处理了拟议的K99研究目标。的 最近发表的初步结果（Menezes et al; 2009）促使PI进一步研究 在ROO阶段调查癌症/颅面异常的关系，PI将继续 调查癌症和颅面畸形之间可能的联系，将研究扩展到 包括先前与颅面异常相关额外基因/位点， 癌症的类型。此外，新的基因和染色体区域以前报道与 在文献中已经报道了几种类型的癌症与颅面异常相关。 最近，PI参与了一项研究，其中8 q24（以前与结肠和前列腺相关的区域） 癌症）也与口裂有关（Beaty等人，2010年）。主要方法将继续是 基因分型和测序程序以及统计遗传学分析。 PI还开始了细胞/组织培养方面的培训，并计划开始进行一些功能研究， 补充他的初步调查结果。这将有助于他实现为原产地规则提出的具体目标 阶段，并能够采集更多的初步数据，以实现更强大的ROI应用程序。

The current proposal seeks activation of tlie ROO phase of a K99R00 award (1K99/R00-DE018413). The PI has completed his K99 main goals: to understand the etiology, epidemiology and phenotypes of oral clefts and to gain expertise in statistical genetics. Also, career development was one ofthe main objectives explored during the K99 phase, with emphasis in Responsible Conduct of Research, Scientific Management Leadership and Ethics. The University of Pittsburgh environment and the infrastructure of the School of Dental Medicine have been essential for the PI progress as an independent scientist. Craniofacial birth defects are the most common type of congenital anomaly in newborns. The etiology of oral clefting is complex, with multiple genetic and environmental influences. It has been proposed in the literature that cancer and congenital malformations may occasionally have a common etiology. The aim of this project is to identify genes that can contribute to both craniofacial anomalies and cancer, and contribute to the better understanding of complex craniofacial and dental genetic disorders. The proposed K99 research aims were well-handled by the PI according to the planned time frame. The preliminary results recently published (Menezes et al; 2009) have motivated the PI to go further in the investigation ofthe cancer/craniofacial anomalies relationship during the ROO phase, the PI will continue to investigate the possible association between cancer and craniofacial anomalies, expanding the studies to include additional genes/loci previously associated with craniofacial anomalies and independentiy with some types of cancer. In additional, new genes and chromosome regions previous reported to be associated with several types of cancers, have been reported to be associated with craniofacial anomalies in the literature. More recently, the PI contributed to a study where the 8q24 (a region previous related to colon and prostate cancer) was also associated with oral clefts (Beaty et al., 2010). The main aproach will continue to be genotyping and sequencing procedures together with statistical genetics analysis. The PI has also started training in cell/tissue culture and is planning to start doing some functional studies to complement his preliminary findings. This will help him accomplish the specific aims proposed for the ROO phase and enable the acquisition of more preliminary data for a stronger ROI application.