| Title: | Investigation of genetic, environment and gene ? environment interaction in colorectal cancer risk and survival |
| Lead Institution: | University of Edinburgh |
| Principal investigator: | Dr Evropi Theodoratou |
Application 7441
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About
We propose to run a) a genome wide association study (GWAS) on colorectal cancer (CRC) survival, b) gene-environment interactions on CRC risk and survival (including gene-25OHD interactions). For these analyses we will include CRC data from UK Biobank and from the Study of Colorectal Cancer in Scotland (SOCCS). The aim of this research will be to identify individuals with poorer prognosis after cancer diagnosis due to either genetic susceptibility or lifestyle. This information can be translated in more effective cancer screening programmes and better prevention policies with the aim of improved prognosis of the high risk groups (by offering more frequent screening or more aggressive treatment after diagnosis). In addition associations between low vitamin D concentrations and CRC will be very important for public health, as vitamin D deficiency is highly prevalent in populations residing at high latitudes or leading an indoors oriented lifestyle. A large number of GWAS studies on cancer risk have been performed that led to the identification of genes that increase the risk of cancer development. However the heritability of cancer survival is poorly understood. Similarly dietary and environmental factors have been linked to cancer risk, but their role in cancer survival has not been widely studied. We are proposing to study these associations by combining the UK Biobank resource with one large study on CRC We also propose to test for the interaction between SNPs and environmental factors (including plasma 25-OHD) in relation to CRC risk and survival. We would like UK Biobank to select the cases and controls for us. The case conrol study will include all the incidence and prevalence CRC cases and a number of disease free individuals equal to four times the number of the total CRC cases. We request the following data for the included cases and controls: GWAS, risk factor, clinical and survival data (including site of tumour, pathological and clinical stage (including AJCC), date of diagnosis, date of death (or loss to follow up), data of blood sample and treatment details (including operation, chemotherapy and radiotherapy)).4 Publications
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 8881 | Association analyses identify 31 new risk loci for colorectal cancer susceptibility | Philip J. Law (+97) | 2019 | Nature Communications |
| 10125 | Circulating 25-hydroxyvitamin D and survival outcomes of colorectal cancer: evidence from population-based prospective cohorts and Mendelian randomisation | Xiaomeng Zhang (+12) | 2024 | British Journal of Cancer |
| 8559 | Exploring causality in the association between circulating 25-hydroxyvitamin D and colorectal cancer risk: a large Mendelian randomisation study | Yazhou He (+27) | 2018 | BMC Medicine |
| 7480 | Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study | Xiaomeng Zhang (+14) | 2021 | British Journal of Cancer |
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