Gender Differences in Bladder Cancer Risk Factors

膀胱癌危险因素的性别差异

• 批准号: 7371977
• 负责人: Christopher A Loffredo
• 金额: $ 42.57万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-11 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371977
• 关键词: Accounting; Affect; Area; Cancer Control; Candidate Disease Gene; Carcinoma; Case-Control Studies; Characteristics; Chemicals; Developed Countries; Egypt; Employee Strikes; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Etiology; Exposure to; Female; Gender; Genes; Genetic Polymorphism; Genetic Predisposition to Disease; Hormonal; Hospitals; Incidence; Infection; Infectious Agent; Infective cystitis; Inflammation; Inflammatory Response; Knowledge; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Mediating; Metabolism; Numbers; Occupational; Occupational Exposure; Oxidative Stress; Parasites; Pathogenesis; Pathway interactions; Pattern; Platelet Factor 4; Population; Prevalence; Preventive; Public Health; Reactive Oxygen Species; Recruitment Activity; Research; Research Infrastructure; Resources; Risk; Risk Factors; Sample Size; Schistosoma haematobium; Schistosoma hematobium infection; Schistosomiasis; Services; Sex Characteristics; Squamous cell carcinoma; Susceptibility Gene; Testing; Time; Tobacco smoke; Transitional Cell; Transitional Cell Carcinoma; Urinary tract infection; Variant; Woman; Work; base; biological adaptation to stress; bladder cancer prevention; bladder transitional cell carcinoma; cancer diagnosis; cancer epidemiology; cancer risk; cancer type; carcinogenesis; cell type; cigarette smoking; gene environment interaction; genetic association; insight; male; men; oncology; regional difference; response

Cancer of the urinary bladder affects 4 to 5 times more men than women worldwide. Cigarette smoking, occupational exposures and infection with Schistosoma haematobium are well-established risk factors for this malignancy. Furthermore, several genetic polymorphisms have been associated with increased bladder cancer risk. Important gaps in knowledge remain about synergistic effects between environmental factors, gene-environment interactions, and gender differences in bladder cancer risk factors. Egypt represents a unique setting for such research, as bladder cancer continues to be the most common malignancy in men in Egypt despite recent reductions in schistosomiasis, and the ratio of men to women remains consistently high; few women in Egypt smoke cigarettes (< 5%) compared to 50-70% of men; and in addition to the transitional cell type carcinoma that is predominantly observed world wide, squamous type carcinoma is very common in Egypt. We therefore propose to conduct a case-control study of bladder cancer in Egypt, with a sample size of 3,312 cases and 4 population-based controls per case. The Specific Aims of the study are as follows: 1) to evaluate environmental risk factors for bladder cancer, in men and women combined, including infections, and interactions among these factors; 2) to determine if associations between risk factors and bladder cancer are affected by gender; 3) to evaluate associations between bladder cancer risk (in men and women combined) and functional polymorphism in genes that mediate the oxidative stress response; 4) to evaluate interactions between environmental exposures and the candidate susceptibility genes, and to determine if gene-environment interactions exert differential effects on bladder cancer risk in men and women. Within these aims we will account for risk differences by histological type of bladder cancer (transitional vs. squamous). The results of this study will help establish the best preventive measures for bladder cancer in men and women, by appropriately directing the resources of the public health sector for effective cancer control.

膀胱癌的影响男性比女性多4至5倍。吸烟、职业暴露和埃及血吸虫感染是这种恶性肿瘤的公认危险因素。此外，几种遗传多态性与膀胱癌风险增加有关。重要的知识差距仍然是关于环境因素，基因-环境相互作用和膀胱癌风险因素的性别差异之间的协同作用。埃及是开展这类研究的独特环境，因为尽管最近血吸虫病有所减少，但膀胱癌仍然是埃及男子最常见的恶性肿瘤，而且男女比例始终很高;埃及妇女很少吸烟（< 5%），而男子吸烟的比例为50-70%;除了在世界范围内主要观察到的移行细胞型癌之外，鳞状细胞型癌在埃及也很常见。因此，我们建议在埃及进行膀胱癌的病例对照研究，样本量为3，312例，每个病例有4个基于人群的对照。本研究的具体目的如下：1）评估男性和女性合并膀胱癌的环境风险因素，包括感染，以及这些因素之间的相互作用; 2）确定风险因素与膀胱癌之间的关联是否受性别影响; 3）评估膀胱癌风险之间的关联（男性和女性合并）和介导氧化应激反应的基因的功能多态性; 4）评价环境暴露与候选易感基因之间的相互作用，并确定基因-环境相互作用是否对男性和女性膀胱癌风险产生不同影响。在这些目标中，我们将根据膀胱癌的组织学类型（过渡性与鳞状）解释风险差异。这项研究的结果将有助于建立男性和女性膀胱癌的最佳预防措施，适当地指导公共卫生部门的资源，以有效地控制癌症。