ROLE OF NUTRITIONAL AND OTHER FACTORS IN ETIOLOGY OF ORAL CANCER

口腔癌是美国的一个主要健康问题；它是一种 死亡率高、发病率高的疾病。虽然风险因素 包括饮酒和吸烟，一些口咽部肿瘤 没有明确的酗酒或吸烟模式。事实上， 在美国增加含酒精的洗口水的使用可能是一种 风险因素。尽管有报道称，新鲜食品的消费 水果和蔬菜与对人体的保护作用有关 高危人群口咽部肿瘤的发生、鉴定 特定的营养成分，例如一种特定的抗氧化剂 预防这种类型的肿瘤的发展还没有得到 成功。不能分离出一种特定的 维生素(例如，β-胡萝卜素)可能是协同保护作用的次要因素 多种饮食成分的影响或先前研究的不足 甲基供应成分，如叶酸或维生素B-12。本地化 叶酸和维生素B-12缺乏可能与 这些肿瘤的发生与活性叶酸和维生素B-12的水平有关 可通过暴露于烟草或其他成分而减少 酗酒。我们假设正常的增殖动态平衡 口腔上皮基底层细胞的数量受到局部因素的影响 叶酸和维生素B-12缺乏以及由此导致的异常 在基底细胞中，酒精和酒精暴露会加剧细胞增殖 烟草产品。最终，细胞增殖增加会增加 中层和高层(即基底层以上)的未成熟细胞 细胞层)，并导致口腔上皮细胞的发育 组织学上可识别的癌前特征 上皮细胞(如异型增生)。这些变化可以通过以下方式识别 局部维生素水平下降和脑组织中 中间终点生物标记物(IEBS)在增生性或发育异常中的作用 上皮组织。我们将根据标准选择要评估的组织 流行病学方法，以验证我们的假设。我们会 从地理角度评价叶酸与维生素B-12水平的关系 上皮细胞内的分布及其与血管病变发生的关系 肿瘤性改变和以下IEBS的表达：TGFα， EGF-R、EGF、p185/crbB-2、转化生长因子-β、脂肪酸合成酶、肿瘤标志物 增殖和P53蛋白的表达。这一建议通过嵌套状态得到加强 最先进的生化、分子和病理评估正常， 癌前病变和鳞状细胞癌在良好的流行病学范围内 对特征良好的患者进行调查。

Oral cancer is a major health problem in the United States; it is a disease of high mortality and severe morbidity. While risk factors include alcohol and tobacco usage, some oro-pharyngeal tumors develop without a defined pattern of alcohol or tobacco abuse. In fact, the increased use of alcohol based mouth washes in the United States may be a risk factor. Although it has been reported that consumption of fresh fruits and vegetables is associated with protective effects on the development of oro-pharyngeal tumors in high risk groups, identification of specific nutritional components such as one specific antioxidant that protects against the development of this type of tumor has not been successful. The inability to isolate a protective effect of a specific vitamin (e.g., beta-carotene) might be secondary to synergistic protective effects of multiple dietary components or to inadequate previous study of methyl supplying components such as folate or vitamin B-12. Localized folate and vitamin B-12 deficiencies may be especially relevant to the development of these tumors since levels of active folate and vitamin B-12 in tissues may be decreased by exposure to components of tobacco or alcohol usage. We hypothesize that the normal proliferative homeostasis of basal cells of the oral epithelium is dysregulated by localized deficiencies of folate and vitamin B-12 and that the resulting abnormality in basal cell proliferation is exacerbated by exposure to alcohol and tobacco products. Ultimately, increased cellular proliferation increases immature cells at intermediate and higher layers (i.e., above the basal cell layer) in the oral epithelium and leads to the development of histologically recognizable pre-malignant characteristics in the epithelium (e.g., dysplasia). These changes can be identified by decreased regional vitamin levels and by changes in the expression of intermediate endpoint biomarkers (IEBs) in the proliferating or dysplastic epithelium. We will select tissues for evaluation based on standard epidemiological methods in order to validate our hypothesis. We will evaluate the relation of folate and vitamin B-12 levels geographically within the epithelium and their correlation with the development of neoplastic changes and with expression of the following IEBs: TGFalpha, EGF-R, EGF, p185/crbB-2, TGF-beta, fatty acid synthetase, markers of proliferation and p53. This proposal is strengthened by nesting state-of- the-art biochemical, molecular, and pathological assessments of normal, pre-malignant and squamous cell cancers within a sound epidemiological investigation of well characterized patients.