Ulrike Peters [firstname.lastname@example.org] and John Potter
Perhaps one-third of colon cancer is attributable to inherited factors. Identifying genetic variants is important to elucidate underlying mechanisms of this, the third leading cause of cancer in US women. We propose a genome-wide association study of nonsynonymous variants, which alter the amino-acid sequence of the protein and are more likely to be functionally relevant. As a secondary aim, we will investigate interactions between genes and environment, including postmenopausal hormone use. We will explore 20,000 single nucleotide polymorphisms (SNPs) including most common nonsynonymous variants in the study population. To balance sample size and cost efficiency, we propose a two-stage design. Stage I will be conducted within an existing colon cancer case-control study (776 cases, 776 matched controls) and stage II, an independent replication of significant findings, will be a nested case-control study within the Women's Health Initiative Observational Study (930 cases, 3720 matched controls). The study is powered to investigate moderate gene-cancer associations (odds ratio of 1.4 for common variants) while eliminating most false positives. Together, the two study populations provide an almost unique resource because of the number of well-characterized cases with DNA samples and detailed exposure assessment. We will use only 1 μg DNA per subject.
We propose the following primary specific aim:
As secondary aims we propose:
Updated Specific Aims as of 10/1/09:
Some of the publications related to this ancillary study are: 962, 1060, 1557, 1566, 1567, 1582, 1689, 1691, 1695, 1726, 1806, 1931, 2057.
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