Gender Differences in Bladder Cancer Risk Factors

全世界患膀胱癌的男性是女性的4到5倍。吸烟、职业接触和感染血吸虫血吸虫是这种恶性肿瘤的公认危险因素。此外，几个基因多态与膀胱癌风险增加有关。关于环境因素之间的协同效应、基因-环境相互作用以及膀胱癌危险因素的性别差异，目前仍存在重要的认识差距。埃及是此类研究的独特环境，因为膀胱癌仍然是埃及男性最常见的恶性肿瘤，尽管最近血吸虫病有所减少，但男性与女性的比例一直很高；埃及很少有女性吸烟(5%)，而男性的吸烟率为50%-70%；除了在世界各地普遍观察到的移行细胞型癌症外，鳞状细胞癌在埃及非常常见。因此，我们建议在埃及进行一项关于膀胱癌的病例对照研究，样本量为3312例，每个病例4个基于人群的对照。该研究的具体目的如下：1)评估膀胱癌的环境风险因素，包括感染，以及这些因素之间的交互作用；2)确定风险因素与膀胱癌的关联是否受性别的影响；3)评估膀胱癌风险(男性和女性合并)与介导氧化应激反应的基因功能多态性的关系；4)评估环境暴露与候选易感基因之间的交互作用，并确定基因与环境的交互作用是否对男性和女性的膀胱癌风险产生不同的影响。在这些目标中，我们将考虑膀胱癌组织学类型(移行细胞癌与鳞癌)的风险差异。这项研究的结果将有助于在男性和女性中建立最佳的膀胱癌预防措施，适当地将公共卫生部门的资源用于有效的癌症控制。

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.