Ten genetic loci for colorectal cancer have been identified from published genome wide association (GWA) studies of colorectal cancer (CRC) and have been robustly replicated in populations of European ancestry. We hypothesize that additional novel risk loci will be identified by joint analyses in which data of approximately 7,000 cases and 7,000 controls from the five existing GWA studies are combined and validated in additional independent samples of cases and controls. In addition, combining genotypic data will allow analyses to be stratified according to demographic and clinico-pathological parameters, and permit studies to identify gene-gene interaction effects that specifically increase CRC risk. Genetic loci identified by pooled analyses will be examined in more detail here in Area 1 """"""""Discovery Expansion and Replication"""""""" as well as Area 3 """"""""Epidemiologic Studies"""""""" in additional case-control studies and nested case-control studies derived from two prospective cohort studies (Melbourne and ACS Cancer Prevention Study II Nutrition Cohort) to determine the extent that these and previously identified common variants are associated with risk. Finally, follow-up fine mapping studies, together with functional analyses in Area 2 - """"""""Biological Studies"""""""", will help to identify the specific causal factors that influence risk of CRC. The goal of this proposal is therefore to establish find new genetic associations through pooled analyses, independently replicate these findings to confirm genotype-phenotype associations, fine-map association signals, and pursue gene-gene interactions with high-density data. The proposed study will comprehensively and efficiently identify new genes that predispose to colorectal cancer. This work has considerable potential to reveal new important targets for cancer prevention and treatment.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRLB-4)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Los Angeles
United States
Zip Code
Boonstra, Philip S; Mukherjee, Bhramar; Gruber, Stephen B et al. (2016) Tests for Gene-Environment Interactions and Joint Effects With Exposure Misclassification. Am J Epidemiol 183:237-47
Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D et al. (2016) Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations. Cancer Res 76:5103-14
Su, Yu-Chen; Gauderman, William James; Berhane, Kiros et al. (2016) Adaptive Set-Based Methods for Association Testing. Genet Epidemiol 40:113-22
Scarbrough, Peter M; Weber, Rachel Palmieri; Iversen, Edwin S et al. (2016) A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 25:193-200
Markowitz, Sanford D; Nock, Nora L; Schmit, Stephanie L et al. (2016) A Germline Variant on Chromosome 4q31.1 Associates with Susceptibility to Developing Colon Cancer Metastasis. PLoS One 11:e0146435
Sanz-Pamplona, Rebeca; Gil-Hoyos, Raúl; López-Doriga, Adriana et al. (2016) Mutanome and expression of immune response genes in microsatellite stable colon cancer. Oncotarget 7:17711-25
Zeng, Chenjie; Matsuda, Koichi; Jia, Wei-Hua et al. (2016) Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk. Gastroenterology 150:1633-45
Schmit, Stephanie L; Rennert, Hedy S; Rennert, Gad et al. (2016) Coffee Consumption and the Risk of Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 25:634-9
Phipps, Amanda I; Passarelli, Michael N; Chan, Andrew T et al. (2016) Common genetic variation and survival after colorectal cancer diagnosis: a genome-wide analysis. Carcinogenesis 37:87-95
Karami, Sara; Han, Younghun; Pande, Mala et al. (2016) Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer 139:2655-2670

Showing the most recent 10 out of 50 publications