Clefts/Craniofacial Anomalies and Cancer Susceptibility

目前的提案寻求激活K99R00奖项的Roo阶段(1K99/R00-DE018413)。《少年派》 已经完成了他的K99主要目标：了解口腔裂隙的病因、流行病学和表型 并获得统计遗传学方面的专业知识。此外，职业发展也是主要目标之一 在K99阶段进行了探索，重点是负责任的研究行为、科学管理 领导力与道德。 匹兹堡大学的环境和牙医学院的基础设施已经 作为一名独立的科学家，这对PI的进步至关重要。头面部出生缺陷是最常见的 新生儿先天畸形的类型。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 可能偶尔会有共同的病因。这项计划的目的是找出有助于 颅面畸形和癌症，有助于更好地理解复杂的颅面 和牙科遗传病。 私隐专员公署按照计划的时间表，妥善处理了建议的K99研究目标。这个 最近公布的初步结果(Meneze等人；2009)促使PI在 Roo期肿瘤/颅面畸形关系的研究，PI将继续 调查癌症和头面部畸形之间的可能联系，将研究范围扩大到 包括以前与颅面畸形相关其他基因/位点，且与一些 癌症的类型。此外，以前报道的新基因和染色体区域与 在文献中，有几种类型的癌症被报道与头面部畸形有关。 最近，PI参与了一项研究，其中8q24(之前与结肠和前列腺有关的区域) (癌症)也与口裂有关(比蒂等人，2010年)。主要的问题将继续是 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 补充了他的初步发现。这将帮助他实现为Roo提出的具体目标 阶段，并支持获取更多初步数据，以实现更高的ROI应用。

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.