Molecular Genetics of Colon Cancer in Blacks and Whites

简介(申请人提供)：结肠癌是第二大病因 尽管人类遗传学取得了快速进展，但美国的癌症死亡人数仍然很多，这一点至关重要 关于结肠癌的遗传易感性和预防的问题 仍然没有答案，特别是对于非洲裔美国人来说，他们有更高的 发病率和死亡率。我们的主要目标是评估基因 可能解释这种差异的易感性和环境因素 黑人和白人的发病率和死亡率趋势。我们的次要目标是 评价基因-基因和基因-环境的作用机制 相互作用，并确定高危(亚)人群和可改变的风险 结肠癌的致病因素。那么就有可能紧密地裁剪 针对特定遗传缺陷的病因学驱动的预防策略 赋予个人风险。我们将评估冒号之间的关联 癌症风险和两个二期代谢解毒基因(GSTM]/T1)，两个 碱基切除修复基因(XRCC1和APE)，双链基因 断裂/重组修复(XRCC3)和核苷酸切除修复基因 (XPD)。拟议的研究将使用现有的基因组DNA样本和 NCI资助的北卡罗来纳州结肠癌研究中收集的暴露数据 (新中国)(加州66635)。NCCCS是一个设计良好、以大量人口为基础、 北卡罗来纳州33个县区800例新发病例对照研究 确诊的结肠癌病例和800名年龄和种族匹配的对照组(50% 黑人和50%的白人)。家长研究正在按目标完成样本 并在我们提出的2002年1月1日开始日期之前收集数据。高潮 黑人参与者的百分比(50%)提供了独特的机会 研究非洲裔美国人的特定危险因素，这是一个研究不足的群体 罹患致命结肠癌的风险增加。大样本量提供了 评估基因-基因和基因暴露的强大统计能力 结肠癌风险中的相互作用。我们的初步试验数据显示 黑人和白人在基因分布和环境暴露方面的差异。 我们还观察了结肠癌中基因-基因和基因-环境的相互作用。 风险。这项拟议的研究将填补结肠癌风险之间的差距 评估和预防。确认风险概况(S)将有助于 确定结肠癌高危人群进行筛查和 干预。基因-环境相互作用的特征将 为饮食和生活方式干预提供有效的策略， 尤其是在遗传易感(亚)人群中。

DESCRIPTION (provided by applicant): Colon cancer is the second leading cause of cancer deaths in the U.S. Despite rapid advances in human genetics, critical questions about genetic susceptibility to, and prevention of, colon cancer remain unanswered, particularly for African-Americans, who have a higher incidence and mortality rate. Our primary objective is to evaluate genetic susceptibility and environmental factors that might explain the diverging incidence and mortality trends in blacks and whites. Our secondary objective is to assess the mechanisms involved in gene-gene and gene-environment interactions and to identify high-risk (sub)populations and modifiable risk factors for colon cancer. Then it may be possible to closely tailor etiology-driven preventive strategies to the specific genetic defects conferring individual risk. We will evaluate the association between colon cancer risk and two phase II metabolic detoxification genes (GSTM]/T1), two base excision repair genes (XRCC1 and APE), a gene in double-strand break/recombination repair (XRCC3), and a nucleotide excision repair gene (XPD). The proposed study will use the existing genomic DNA samples and exposure data collected in the NCI-funded North Carolina Colon Cancer Study (NCCCS) (CA 66635). The NCCCS is a well-designed, large population-based, case-control study in a 33-county area of North Carolina with 800 newly diagnosed colon cancer cases and 800 age- and race-matched controls (50 percent blacks and 50 percent whites). The parent study is on target to complete sample and data collection by our proposed start date of January 1, 2002. The high percentage of black participants (50 percent) provides the unique opportunity to study specific risk factors in African-Americans, an understudied population at increased risk of fatal colon cancer. The large sample size provides substantial statistical power for the assessment of gene-gene and gene-exposure interactions in colon cancer risk. Our preliminary pilot data demonstrated black-white differences in genotype distributions and environmental exposures. We also observed gene-gene and gene-environment interactions in colon cancer risk. This proposed research will fill the gap between colon cancer risk assessment and prevention. Confirmation of risk profile(s) will be useful in identifying persons at high risk of colon cancer for screening and intervention. Characterization of gene-environment interactions will provideeffective strategies for dietary and lifestyle interventions, particularly in genetically susceptible (sub)populations.