Molecular Genetics of Colon Cancer in Blacks and Whites

描述（由申请人提供）：结肠癌是第二大原因 尽管人类遗传学取得了迅速进展，但关键是 结肠癌的遗传易感性和预防问题 仍然没有答案，特别是对非洲裔美国人来说，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 易感性和环境因素，可能解释的分歧， 黑人和白人的发病率和死亡率趋势我们的次要目标是 评估基因-基因和基因-环境的机制 相互作用，并确定高风险（亚）人群和可改变的风险 结肠癌的病因那么就有可能 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。我们将评估结肠癌与 癌症风险和两个II期代谢解毒基因（GSTM]/T1），两个 碱基切除修复基因（XRCC 1和APE），双链中的基因 断裂/重组修复（XRCC 3）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， 由美国国家癌症研究所资助的北卡罗来纳州结肠癌研究中收集的暴露数据 （NCCCS）（CA 66635）。NCCCS是一个精心设计的，基于大量人口的， 在北卡罗来纳州的33个县进行了一项病例对照研究， 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）。母研究的目标是完成样本 和数据收集，我们建议的开始日期2002年1月1日。高 黑人参与者的百分比（50%）提供了独特的机会， 研究非裔美国人的特定风险因素， 会增加患致命结肠癌的风险大样本量提供了 评估基因-基因和基因-暴露的显著统计功效 结肠癌风险的相互作用。我们初步的试验数据表明 基因型分布和环境暴露的黑白差异。 我们还观察了结肠癌中基因-基因和基因-环境的相互作用 风险这项拟议中的研究将填补结肠癌风险与健康风险之间的差距。 评估和预防。确认风险简介将有助于 确定结肠癌高危人群进行筛查， 干预基因-环境相互作用的表征将 为饮食和生活方式干预提供有效的策略， 特别是在遗传易感（亚）群体中。

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.